@article {pmid43023737,
year = {2026},
author = {Quilbé, J and Mouritzen, TW and Akyol, TY and Mustamin, Y and Bamba, M and Schierup, MH and Sato, S and Andersen, SU},
title = {ROOMIE1 controls rhizobiome assembly in Lotus japonicus and shows a genomic signature distinct from climate-associated loci.},
journal = {The New phytologist},
volume = {},
number = {},
pages = {},
doi = {10.1111/nph.71756},
pmid = {43023737},
issn = {1469-8137},
support = {NNF19SA0059362//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; },
abstract = {How plant genomes accommodate selective pressures across spatial and temporal scales remains poorly understood. Here, we address this by comparing the population-genomic signatures of root microbiome- and climate-associated loci in a natural Lotus japonicus population. We inoculated 155 L. japonicus accessions with a synthetic community of 107 bacterial isolates and performed genome-wide association analyses of rhizosphere microbiome traits. We then carried out functional validation, testing effects of mutations and natural allelic variation, and compared population-genomic characteristics of microbiome-associated and climate-associated loci. We identified 355 significant quantitative trait loci associated with rhizosphere microbiome variation. Microbiome-associated loci showed heterogeneous genomic signatures. One subset displayed strong regional differentiation and near fixation of specific haplotypes, whereas another showed low differentiation, and maintenance of multiple haplotypes within populations. The latter pattern was exemplified by ROOT MICROBIOME ESTABLISHMENT 1 (ROOMIE1). Disruption of ROOMIE1 reproducibly altered rhizosphere microbiome composition in both synthetic communities and native soil, whereas natural ROOMIE1 haplotypes were associated with microbiome differences among closely related accessions. Our findings reveal that microbiome-associated loci can display population-genomic signatures that sharply contrast with those at climate-associated loci, with ROOMIE1 representing a host gene that controls rhizosphere microbiome composition and shows standing haplotype variation at a local scale.},
}

@article {pmid43023739,
year = {2026},
author = {Lietuvninkas, HB and Cullum, E and Denzin, L and Golovkina, T},
title = {H2-O deficiency is associated with altered intestinal bacterial communities and differential IgG binding.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0069226},
doi = {10.1128/msphere.00692-26},
pmid = {43023739},
issn = {2379-5042},
abstract = {The non-classical major histocompatibility complex class II (MHCII) molecule H2-O regulates peptide loading by inhibiting H2-M, thereby restricting the repertoire of high-affinity peptides presented to CD4[+] T cells. H2-O deficiency enhances protective immunoglobulin G (IgG) responses against pathogens, including retroviruses and Staphylococcus aureus, and promotes the generation of IgG specific for the commensal bacterium Staphylococcus xylosus. Whether these expanded antibody responses influence intestinal microbial communities is unknown. Here, using gnotobiotic mouse models, we demonstrate that H2-O shapes the gut bacterial composition to a limited but significant extent. H2-O deficiency was associated with increased serum IgG reactivity against commensal microbial antigens (Ags). Sequencing antibody-coated bacteria revealed distinct populations between H2-O-deficient and H2-O-sufficient mice within the IgG-coated, but not IgA-coated, fractions. Together, these findings identify an association between H2-O genotype and microbiome composition and reveal differential IgG, but not IgA, binding to intestinal bacterial communities. These results expand current understanding of how Ag presentation pathways influence host-microbiome interactions and suggest a potential relationship between regulation of the MHCII peptidome, IgG responses, and commensal ecology.IMPORTANCEOur findings demonstrate that the absence of H2-O not only promotes protective IgG responses against retroviruses and Staphylococcus aureus but also is associated with altered intestinal IgG binding patterns and differences in gut microbiome composition.},
}

@article {pmid43023958,
year = {2026},
author = {Yuzefpolskaya, M and Bertoni, AG and Colombo, PC and Demmer, RT},
title = {The Gut-Heart-Muscle Hypothesis in Heart Failure: Emerging Associations, Mechanistic Uncertainty, and the Potential Role of Exercise.},
journal = {JACC. Heart failure},
volume = {},
number = {},
pages = {103501},
doi = {10.1016/j.jchf.2026.103501},
pmid = {43023958},
issn = {2213-1787},
}

@article {pmid43023986,
year = {2026},
author = {Zhang, L and Yao, Y and Cai, X},
title = {Inflammaging and Cellular Senescence in Postmenopausal Depression: Linking Estrogen Deficiency, Immune Dysregulation, and Brain Aging.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {22},
pages = {},
pmid = {43023986},
issn = {1530-6860},
support = {2025ZR012//Zhejiang Province Traditional Chinese Medicine Science and Technology Project/ ; },
mesh = {Humans ; Female ; *Estrogens/deficiency ; *Cellular Senescence ; *Brain/metabolism/pathology ; *Aging/immunology ; *Postmenopause ; *Depression/metabolism/immunology ; Animals ; *Inflammation/immunology ; },
abstract = {Postmenopausal depression is clinically heterogeneous and cannot be explained by estrogen deficiency alone. We propose a conceptual, testable neuroimmune-aging model in which endocrine decline may interact with inflammaging, cellular senescence, and brain vulnerability in a subset of women. The evidentiary base is uneven: direct studies of senescence in well-phenotyped postmenopausal depression are lacking; clinical endocrine data come mainly from perimenopausal depression; molecular-senescence findings come from late-life depression or general major depressive disorder; and most cellular and brain mechanisms are supported by aging or preclinical models. Reduced estrogen signaling may weaken immune homeostasis, whereas peripheral cytokines or senescence-associated secretory phenotype factors could influence vascular and neural interfaces, glia, neurotransmitter metabolism, stress signaling, mitochondrial function, and neuroplasticity. These pathways are candidate mediators, not established causal mechanisms. Clinically established care remains diagnosis-based antidepressant treatment, evidence-based management of vasomotor and sleep symptoms, and individualized menopausal hormone therapy for appropriate candidates. Anti-inflammatory, microbiome-based, and senescence-targeted strategies remain investigational; no senolytic or senomorphic is approved for depression or menopause-related mood symptoms. Prospective studies integrating menopausal staging, prespecified confounders, senescence biomarkers, neuroimaging, and mood outcomes are needed to test this model.},
}

Humans
Female
*Estrogens/deficiency
*Cellular Senescence
*Brain/metabolism/pathology
*Aging/immunology
*Postmenopause
*Depression/metabolism/immunology
Animals
*Inflammation/immunology

@article {pmid43023992,
year = {2026},
author = {Lin, YC and Wu, CY and Wang, MC and Cheng, HY and Meng, YZ and Chang, HJ and Hung, JH and Wang, YC and Lin, TH and Tseng, YC and Hsu, CC and Chang, CW and Yang, SH},
title = {Microbiome Flexibility and Metabolomic Buffering in Octocorals During Environmental Acclimation.},
journal = {Microbial ecology},
volume = {89},
number = {1},
pages = {},
pmid = {43023992},
issn = {1432-184X},
support = {NSTC 112-2311-B-002-017-MY3//National Science and Technology Council/ ; NTU-114V1034-3//Ministry of Education/ ; NTUCCP- 114L892606//National Taiwan University/ ; },
mesh = {Animals ; *Anthozoa/microbiology/physiology/metabolism ; *Acclimatization ; *Microbiota ; *Bacteria/classification/genetics/isolation & purification/metabolism ; *Metabolome ; RNA, Ribosomal, 16S/genetics ; Multiomics ; Metabolomics ; Symbiosis ; },
abstract = {Octocorals are keystone reef species and sources of valuable bioactive compounds, yet the microbial dynamics underlying their acclimation to cultivation remain poorly characterized. We examined whether transplanted corals would show differential recovery trajectories between bacterial community and metabolome, and explored the potential role of microbial functional redundancy in shaping holobiont resilience. To address this, we analyzed a 19‑week multi‑omics time series dataset (16S rRNA sequencing, amino‑acid and lipid profiling) from transplanted octocorals, Lobophytum sp. and Sclerophytum sp., benchmarked against wild reef baselines. Bacterial communities diverged initially, converged by week 12, and re‑diverged by week 19, whereas metabolomes consistently converged toward wild norms despite species-specific variations. Integration of microbial and metabolomic data further revealed that microbe-metabolite associations were restructured across environments, consistent with environment-driven reorganization of holobiont interactions. These findings characterize the temporal dynamics of octocoral bacterial communities during acclimation and identify metabolomic stability as a complementary indicator of holobiont resilience, with implications for monitoring and optimizing octocoral cultivation.},
}

Animals
*Anthozoa/microbiology/physiology/metabolism
*Acclimatization
*Microbiota
*Bacteria/classification/genetics/isolation & purification/metabolism
*Metabolome
RNA, Ribosomal, 16S/genetics
Multiomics
Metabolomics
Symbiosis

@article {pmid43024025,
year = {2026},
author = {Chigozie, VU and Oghonyon, EI and Enyi, EO},
title = {Environmental Microbiomes as Sources of Postbiotic Therapeutics: A One Health Perspective on Translational Applications.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {43024025},
issn = {1867-1314},
abstract = {Environmental microbiomes are reservoirs of specialized microorganisms with implications for ecosystem functionality, host health, and therapeutic discovery. Soil, marine, plant-associated, wastewater, freshwater, and extreme-environment microbiomes contain communities capable of producing bioactive metabolites and functional biomolecules. Postbiotics-non-viable microorganisms and their functional components that confer health benefits-offer potential advantages in stability, safety, scalability, and pharmaceutical development. This review examines environmental microbiomes as sources of postbiotic therapeutics within a One Health framework. A critical integrative translational review synthesized literature on environmental microbiomes, postbiotic diversity, molecular mechanisms, therapeutic applications, technological advances, and barriers to clinical translation. Evidence was organized across ecological sources, postbiotic classes, human-health applications, discovery platforms, pharmaceutical development, and translational challenges. Environmental microbiomes represent chemically and functionally diverse reservoirs of postbiotic candidates shaped by ecological adaptation, microbial competition, and environmental selection. Major classes-including short-chain fatty acids, bacteriocins, extracellular vesicles, indole and tryptophan metabolites, exopolysaccharides, and microbial/lytic enzymes-act through receptor signaling, immune modulation, barrier protection, antimicrobial activity, metabolic regulation, intercellular communication, and enzymatic target modification. Metagenomics, metabolomics, artificial intelligence, synthetic biology, organoid and microfluidic models, advanced delivery systems, and biomanufacturing increasingly enable discovery and development. However, reproducibility, microbiome variability, manufacturing scalability, regulatory standardization, cost, and equitable translation remain barriers. Environmental microbiomes provide important reservoirs for postbiotic discovery. Integrating ecological microbiology with multi-omics, computational innovation, pharmaceutical engineering, and human-relevant validation could accelerate development of defined, reproducible, and scalable postbiotic therapeutics. Preserving microbial ecosystem diversity is relevant to environmental sustainability and future microbiome-derived therapeutic innovation within One Health medicine.},
}

@article {pmid43024026,
year = {2026},
author = {Zhu, Z and Xu, F and Yin, D and Shao, Y},
title = {The Application of Engineered Probiotics in the Prophylaxis and Control of Salmonella Infections.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {43024026},
issn = {1867-1314},
support = {KJCX20261009//Beijing Academy of Agricuture and Forestry Sciences/ ; 32202679//National Natural Science Foundation of China/ ; XMS202616//Beijing Academy of Agricultural and Forestry Sciences/ ; },
abstract = {Salmonella is a major zoonotic pathogen responsible for human and animal infections, posing significant challenges to public health and disease control. Its pathogenicity relies on a suite of molecular mechanisms mediating bacterial adhesion, invasion, intracellular persistence, immune evasion, and host-microbe crosstalk. Conventional probiotics mitigate Salmonella infection through competitive exclusion, secretion of antimicrobial metabolites, intestinal barrier reinforcement, microbiota remodelling and host immunomodulation. However, their efficacy varies depending on strain, host, dose, formulation, delivery route, infection model, and intervention timing. Genetically engineered probiotics and complementary non-genetic functional enhancement strategies offer opportunities to introduce or tailor defined antimicrobial, biosensing, colonisation or ecological functions. This narrative review summarizes recent progress in genetically engineered probiotics, non-genetic functional enhancement of probiotics, and attenuated pathogen strains for Salmonella control. Genetically engineered probiotics are equipped with programmable regulatory and antibacterial modules, while non-genetic probiotic approaches include probiotic-nanomaterial biohybrids, metabolically adapted strains and microbiome-directed substrate interventions. Preclinical studies show these microbial systems can provide programmable, targeted, context-dependent functions to reduce Salmonella colonisation, though their performance is also highly context-dependent. Future studies should focus on improving functional stability, standardizing efficacy and biosafety evaluation, clarifying ecological and environmental risks, and addressing manufacturing, formulation, quality-control, and regulatory requirements for translational development.},
}

@article {pmid43024207,
year = {2027},
author = {Vaddi, P and Lynch, DB and Hill, CM},
title = {Characterizing Gut Diversity During Aging.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3105},
number = {},
pages = {189-200},
pmid = {43024207},
issn = {1940-6029},
mesh = {Animals ; *Aging ; Mice ; RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; Shotgun Sequencing ; *Bacteria/genetics/classification ; Biodiversity ; },
abstract = {Microbiome Protocols and Analyses are commonly reported with 16S sequencing in young animals. Our protocol aims to establish a standardized method for shotgun sequencing to improve the resolution of differentially expressed bacteria in aging mice, which otherwise have low alpha and beta diversity.},
}

Animals
*Aging
Mice
RNA, Ribosomal, 16S/genetics
*Gastrointestinal Microbiome/genetics
Shotgun Sequencing
*Bacteria/genetics/classification
Biodiversity

@article {pmid43024340,
year = {2026},
author = {Rubin, R},
title = {After COVID-19 Vaccination, Why Do Some People Run a Fever?.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.22638},
pmid = {43024340},
issn = {1538-3598},
}

@article {pmid43024505,
year = {2026},
author = {Buchanan, LB and Khan, Y and Rojas-Vargas, J and Shao, Z and Biribawa, VM and Ssemunywa, HR and Namuniina, A and Okech, B and Tobian, AAR and Park, DE and Liu, CM and Kaul, R and Galiwango, RM and Prodger, JL},
title = {CD11c+ dermal dendritic cells are abundant HIV target cells in the foreskin and are increased in men with HIV-associated penile anaerobes.},
journal = {Cell reports},
volume = {45},
number = {11},
pages = {118330},
doi = {10.1016/j.celrep.2026.118330},
pmid = {43024505},
issn = {2211-1247},
abstract = {HIV-associated penile anaerobes are associated with reduced epithelial barrier proteins and increased foreskin T cell density, but their relationships with myeloid populations remain unexplored. We analyzed inner foreskin tissues and penile microbiome data from 116 HIV-negative Ugandan men undergoing voluntary medical male circumcision. Quantitative immunofluorescence showed 48.6% of cells expressing the HIV entry receptors, CD4 and CCR5, co-express CD11c. Men with a high abundance of bacteria associated with HIV seroconversion and immune cells (BASIC species) had a greater density of foreskin dermal CD11c+ dendritic cell 2 (DC2) populations. Integration with previously published foreskin cytokine data revealed that the density of foreskin CD207-negative DC2 cells was positively correlated with concentrations of IL-1α, IL-1β, IL-8, CCL4, MMP-9, and resistin. These cross-sectional findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible dermal dendritic cells, alongside increased T cells and epithelial disruption.},
}

@article {pmid43024513,
year = {2026},
author = {Aeschlimann, L and Nassirnia, S and Bouzourene, N and Clavien, C and Bangerter, M and Gilardi, F and Thomas, A and Greub, G and Boutrel, B and Bertelli, C and Rossetti, C},
title = {Dysregulated microbiota-gut-brain axis induced by intermittent access to palatable food is associated with binge-like eating regardless of obesity development.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2756714},
doi = {10.1080/19490976.2026.2756714},
pmid = {43024513},
issn = {1949-0984},
mesh = {Animals ; Female ; *Obesity/microbiology/metabolism/physiopathology ; Rats ; Leptin/metabolism ; *Gastrointestinal Microbiome ; *Bulimia/microbiology/metabolism/physiopathology ; *Brain-Gut Axis/physiology ; Rats, Sprague-Dawley ; Hypothalamus/metabolism ; Bacteria/classification/isolation & purification/genetics ; Brain ; },
abstract = {Recurrent consumption of energy dense palatable foods contributes to the rising prevalence of obesity and can also promote loss-of-control eating in a subset of individuals. Obesity is commonly associated with peripheral inflammation, impaired sensitivity to appetite-regulating hormones, and alterations in gut microbiota composition, all of which may exacerbate binge-eating behaviors. However, emerging evidence suggests that repeated exposure to palatable foods alone can induce maladaptive eating patterns even prior to the development of obesity. In this study, intermittent access to palatable food (e.g., cheesecake) induced binge-like eating behavior in non-obese female rats, accompanied by hypothalamic microglial reactivity and altered leptin signaling pathway. Additionally, even sporadic exposure to palatable food was sufficient to alter gut microbiota composition, increasing microbial diversity and promoting taxa adapted to high fat and sugar availability, including potential pathobionts (e.g., Escherichia, Streptococcus, and Clostridium spp.) as well as carbohydrate-fermenting bacteria such as Bifidobacterium and Roseburia. Notably, increased microbial diversity was associated with both hyperphagic behavior and reduced hypothalamic leptin pathway responsiveness. Overall, these findings suggest that gut microbiota imbalance and central neuroimmune adaptations occurred in the absence of significant weight gain. This highlights the potential value of early interventions which may represent promising candidate strategies for future investigation.},
}

Animals
Female
*Obesity/microbiology/metabolism/physiopathology
Rats
Leptin/metabolism
*Gastrointestinal Microbiome
*Bulimia/microbiology/metabolism/physiopathology
*Brain-Gut Axis/physiology
Rats, Sprague-Dawley
Hypothalamus/metabolism
Bacteria/classification/isolation & purification/genetics
Brain

@article {pmid43025162,
year = {2026},
author = {Amin, A and Zaman, W and Ullah, A},
title = {Root-inspired selective biofilm control: Design principles for programmable interfaces.},
journal = {Microbiological research},
volume = {315},
number = {},
pages = {128823},
doi = {10.1016/j.micres.2026.128823},
pmid = {43025162},
issn = {1618-0623},
abstract = {Most antifouling technologies delay attachment, kill colonizers, or remove biomass. Plant roots instead preserve water and nutrient exchange while regulating dense microbial communities through zonation, hydrated mucilage, patterned metabolite release, immunity, competition, and selective recruitment. This critical review develops a root-inspired framework for selective biofilm control: a bounded, functionally defined community that remains below application-specific limits for coverage, harmful activity, and asset impairment, and can be reset when those limits are exceeded. We distinguish established rhizosphere biology and materials evidence from proposed engineering translations. We examine renewable hydrated layers, spatial chemical fields, conditional sensing and response, and context-dependent priority effects, integrating them with biofilm matrix, mechanics, dispersal, and polymicrobial tolerance. We propose that programmable interfaces combine a low-fouling base, renewable outer layer, local cues, and feedback based on measured performance. The framework is a design hypothesis rather than a validated integrated technology. Translation requires local-field measurements, causal controls, realistic mixed-community ageing tests, repeated reset cycles, and application-specific safety assessment. Sterile exclusion remains preferable where any viable colonization is unacceptable.},
}

@article {pmid43025194,
year = {2026},
author = {Ohbayashi, Y and Imataki, O and Takeuchi, A and Sakaji, M and Ishida, T and Uchida, S and Uemura, M and Nakayama-Imaohji, H and Tada, A and Kuwahara, T and Miyake, M},
title = {Longitudinal dynamics of the oral microbiota during allogeneic hematopoietic stem cell transplantation: an exploratory study with complementary gut microbiota analysis.},
journal = {Journal of oral biosciences},
volume = {68},
number = {6},
pages = {100836},
doi = {10.1016/j.job.2026.100836},
pmid = {43025194},
issn = {1880-3865},
abstract = {OBJECTIVES: The oral microbiota undergoes substantial ecological disruption during allogeneic hematopoietic stem cell transplantation (allo-HSCT), potentially contributing to systemic infections. Although allo-HSCT-associated gut microbiota dysbiosis has been extensively investigated, longitudinal changes in oral microbiota and their relationship with bloodstream infections (BSIs) remain incompletely understood. We therefore aimed to characterize longitudinal changes in oral and gut microbiota and examine their association with BSIs.

METHODS: We prospectively analyzed the oral and gut microbiota of 16 adult allo-HSCT recipients using 16S rRNA gene sequencing. Salivary and fecal samples were collected before transplantation, on the day of transplantation, during neutropenia, at engraftment, and after engraftment.

RESULTS: Six patients developed 11 BSI episodes, with the first episode in each patient occurring at a median of 8 days after transplantation. Staphylococcus haemolyticus was the most common pathogen (7/11 episodes), followed by Enterococcus faecium (2/11 episodes). The oral microbiota underwent marked longitudinal alterations throughout the transplantation period, accompanied by similar changes in the gut microbiota. Differences in microbiota trajectories were observed between patients with and without BSIs despite comparable cumulative antibiotic exposure. Oral-associated genera, including Streptococcus, Fusobacterium, Veillonella, Actinomyces, and Lautropia, were detected in fecal samples, suggesting possible oral-to-gut translocation.

CONCLUSIONS: The oral and gut microbiota underwent substantial longitudinal alterations during allo-HSCT. Differences in microbiota dynamics between patients with and without BSIs were not explained solely by antibiotic exposure. These exploratory findings provide insights into the timing of oral and gut microbiota alterations during allo-HSCT and highlight potential relationships between oral and gut microbial changes and BSIs.},
}

@article {pmid43025213,
year = {2026},
author = {Dey, P},
title = {Dietary shifts across human evolution reveal a progressive loss of gut microbial diversity and functions.},
journal = {Nutrition research (New York, N.Y.)},
volume = {155},
number = {},
pages = {214-232},
doi = {10.1016/j.nutres.2026.10.009},
pmid = {43025213},
issn = {1879-0739},
abstract = {This narrative review summarizes the evolutionary, archaeological, and metagenomic evidence to illustrate how significant dietary shifts, from Paleolithic hunter-gatherer lifestyles to Neolithic agricultural practices and ultimately to modern industrial diets, have gradually transformed the human gut microbiome. The objective is to position diet as a dominant influence on gut microbial evolution, and to demonstrate that the contemporary Western diet signifies a profound divergence from the nutritional context to which our microbiota has coevolved over thousands of years. The available data uncovers three main conclusions. First, hunter-gatherer communities exhibit remarkably elevated α-diversity, a predominance of Prevotella and Treponema, and an abundance of cellulose-degrading Ruminococcus, which together facilitate substantial short-chain fatty acid synthesis. Second, comparative studies reveal a notable shift from Prevotella to Bacteroides in industrialized societies, along with a substantial decline in microbial diversity and a deterioration of carbohydrate-metabolizing pathways. Third, preindustrial gut microbiota were fundamentally different from Westernized ones, emphasizing that both dietary processing and food type influenced the evolution of human gut microbiota. Collectively, the modern industrial diet has created an evolutionary discord, leading to the gradual decline of ancient microbial lineages and their metabolic capabilities. This functional deterioration, especially in fiber fermentation and short-chain fatty acid production, is mechanistically associated with the increase of chronic inflammatory and metabolic disorders. These observations establish a historical reference point for gut microbiota composition, highlighting that dietary rewilding and targeted microbial restoration are empirically supported methods for mitigating contemporary dysbiosis.},
}

@article {pmid43025279,
year = {2026},
author = {Zhu, W and Liu, X and Qiu, Z and Zhang, J and Zhao, H and Rinkevich, B and Yang, P and Wang, A and Li, X},
title = {Hidden depths: Divergent microbiome trajectories as indicators of growth performance in long-term coral transplantation.},
journal = {Marine environmental research},
volume = {223},
number = {},
pages = {108553},
doi = {10.1016/j.marenvres.2026.108553},
pmid = {43025279},
issn = {1879-0291},
abstract = {Growing evidence highlights the coral microbiome as a critical regulator of host acclimation to new environments and a promising source of information for evaluating transplantation performance. In this 16-month study, we conducted long-term repeated monitoring (10 sampling events) of Acropora hyacinthus at two depths to examine coral performance and bacterial dynamics. Corals transplanted in shallow-water transplantation sites showed significantly lower survival and impaired growth rates compared to those in deep-water transplantation sites. Microbial community analyses revealed that deep-water transplants maintained resilient, U-shaped alpha and beta diversity trajectories, whereas shallow-water transplants experienced a continuous decline in diversity, alongside a positive correlation between microbial diversity and coral growth. This trend was consistent with the stronger determinism exhibited by stressed shallow-water corals over time, suggesting that growth performance may be associated with a moderate balance between deterministic and stochastic assembly processes. Random Forest modeling identified core bacterial taxa that exhibited stronger associations with growth rate than diversity-based metrics and assembly processes, highlighting their potential as candidate biomarkers. Together, these findings suggest that selecting well-matched transplantation sites and incorporating microbiome-based monitoring may help inform early-stage restoration strategies and improve cost-effectiveness. However, more refined transplantation designs and broader spatiotemporal replication are needed to confirm these associations and disentangle transplantation effects from potential confounders.},
}

@article {pmid43025328,
year = {2026},
author = {Khan, A and Vasquez, DEC and Si, Y and Vidar, WS and Wu, K and Chiu, N and Jia, Z},
title = {Chronic polystyrene nanoplastics exposure reprograms gene expression, alternative splicing, and disrupts host-microbiome-metabolic networks to promote atherosclerosis in LDLr[-]/[-] mice.},
journal = {Journal of hazardous materials},
volume = {519},
number = {},
pages = {144190},
doi = {10.1016/j.jhazmat.2026.144190},
pmid = {43025328},
issn = {1873-3336},
abstract = {Micro- and nanoplastics have been detected in human blood and carotid atheromas, yet their mechanistic contribution to atherogenesis is poorly defined, and chronic exposure studies of nanoplastics are limited. This multi-omics study investigates chronic (12-week) oral exposure to 80 nm polystyrene nanoplastics in LDLr[-]/[-] mice, integrating aortic plaque quantification, hepatic transcriptomics with alternative splicing profiling, gut microbiome 16S sequencing, and liver untargeted metabolomics into a unified host-microbiome-metabolite network. Nanoplastics increased aortic lipid deposition, suppressed hepatic detoxification and anti-atherogenic lipid pathways at the transcriptional and post-transcriptional levels including alternative splicing events. Exposure induced gut dysbiosis, reduced SCFA-producing commensals and enriched pro-atherogenic pathobionts, shifts co-occurring directionally with hepatic transcriptional modules. Hepatic genes (down-regulated Fbp1, Ccn1 and Cyp2c29; upregulated Chka) and gut genera (depleted Bacteroides; enriched Faecalibaculum and Streptococcus) were confirmed by RT-qPCR and genus-specific qPCR. Untargeted metabolomics showed elevated aromatic and branched-chain amino acids such as tryptophan and methionine, and depletion of glutathione precursor γ-glutamylcysteine and the antioxidant taurine, implicating oxidative stress and amino-acid dysregulation. Concordance with human MASLD (GSE135251) and atherosclerotic plaque (GSE100927) transcriptomes and gut signatures matching human atherosclerotic microbiome profiles suggest plausibility for human relevance. This research implicates nanoplastics as a cardiovascular risk factor involving splicing reprogramming and gut-liver crosstalk.},
}

@article {pmid43025334,
year = {2026},
author = {Niedermeier, LS and Burrichter, AG and Matchado, MS and Stecher, B},
title = {The OMM[12] model after ten years: what did we learn about the gut microbiome from a defined microbial community?.},
journal = {Current opinion in microbiology},
volume = {94},
number = {},
pages = {102849},
doi = {10.1016/j.mib.2026.102849},
pmid = {43025334},
issn = {1879-0364},
abstract = {Over the past decade, the Oligo-Mouse-Microbiota (OMM[12]) has emerged as a cornerstone model for mechanistic studies of the gut microbiome. As a rationally designed, defined microbial community, OMM[12] reduces the complexity of the native microbiota while preserving key ecological and functional traits of the murine gut ecosystem. Comprising twelve culturable, genome-sequenced, and phenotypically characterized strains of murine origin, the model enables reproducible and stable colonization across hosts and experimental settings. Initially developed to study colonization resistance, OMM[12] has since been widely applied across diverse fields, including microbial ecology, immunology, and computational biology, providing fundamental insights into host-microbe and microbe-microbe interactions. Its broad adoption has been supported by the development of a rich experimental and computational toolbox, including strain-resolved sequencing, metabolomics, and metabolic modeling approaches. Here, we review a decade of OMM[12] research, highlighting its design principles, methodological advances, and key scientific discoveries, and we additionally provide an overview of available resources, including a newly established website (daisybio.ls.tum.de/omm12/) that consolidates tools, protocols, and datasets to facilitate community use. Together, this review underscores the continued importance of OMM[12] as a versatile platform for causal and quantitative microbiome research.},
}

@article {pmid43025458,
year = {2026},
author = {Peters, S and Tessmer, L and Dignass, A and Stein, J},
title = {[Adjunctive enteral nutrition in Crohn's disease during biologic therapy: More than a supportive measure? A narrative review].},
journal = {Zeitschrift fur Gastroenterologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2992-6044},
pmid = {43025458},
issn = {1439-7803},
abstract = {OBJECTIVE: This narrative review aimed to critically evaluate evidence for combining enteral nutrition (EN) with biologic therapy in adults with Crohn's disease (CD).

METHODS: PubMed, Embase and the Cochrane Library were searched on EN combined with biologics, incl. infliximab, adalimumab, vedolizumab, and ustekinumab. Studies published from 01/2018-06/2026 and current clinical guidelines were considered. The evidence was evaluated regarding clinical effectiveness and methodological limitations.

RESULTS: Current evidence suggests that adding enteral nutrition to biologic therapy may relatively increase clinical and endoscopic remission rates by up to 50 % compared with biologic monotherapy. The potential benefit may be due to enhanced mucosal healing, alterations in the intestinal microbiome, and improved pharmacokinetics. Higher rates of transmural healing and lower relapse, treatment escalation, and surgery rates have also been reported. While exclusive EN has a broader evidence base, partial EN may offer advantages in clinical practice because of its greater feasibility and acceptability. Evidence is limited by selection bias, heterogeneous treatment protocols and lack of blinding.

CONCLUSION: Combining EN with biologics is a promising therapeutic approach for adults with CD. Prospective RCTs are needed to establish efficacy, safety and optimal use of exclusive and partial EN.},
}

@article {pmid43025481,
year = {2026},
author = {Bórquez, A and Poveda, SL and Hamamé, M and Lobos, J and Pardo, LM},
title = {Black spot Shell syndrome in the marble crab Metacarcinus edwardsii from northern Chilean Patagonia: Prevalence and associated bacterial assemblages.},
journal = {Journal of invertebrate pathology},
volume = {},
number = {},
pages = {108791},
doi = {10.1016/j.jip.2026.108791},
pmid = {43025481},
issn = {1096-0805},
abstract = {Black spot shell syndrome is a polymicrobial shell disease of crustaceans that can impair host fitness and reduce fishery value, yet it has not previously been documented in the marble crab, Metacarcinus edwardsii, in Chile. This study characterised the prevalence of black spot shell syndrome and the associated culturable bacterial assemblage in M. edwardsii from northern Chilean Patagonia. In August 2023, 2518 crabs were sampled across three fishing grounds in the Aysén Region and examined for lesion presence, lesion coverage and host traits, while bacteria from unaffected and affected carapaces were cultured and identified by 16S rRNA gene sequencing. Overall prevalence was 13.7%; occurrence differed among sites, increased with carapace width and was not associated with sex. Among affected crabs, lesion coverage also varied among sites and showed no association with sex or carapace width. Forty-three bacterial isolates representing seven genera were recovered, with members of the Pseudomonas fluorescens species complex predominating across lesion stages. Several Pseudomonas isolates exhibited chitinolytic and proteolytic activities consistent with a potential role in cuticle degradation. However, these findings do not establish Pseudomonas as the primary aetiological agent of the syndrome. These findings provide the first epidemiological and microbiological baseline evidence of black spot shell syndrome in M. edwardsii in Chile and highlight the need for continued surveillance, culture-independent microbiome profiling and targeted pathogenicity studies.},
}

@article {pmid43025506,
year = {2026},
author = {Song, Y and Li, Z and Wang, M and Hong, J and Zhang, Y and Zuo, J and Peng, H and Yuan, B and Jin, Y},
title = {An oral delivery platform for protein drugs: PDA/PEGylated engineered probiotics responsively release TLR5 agonists to prevent radiation enteritis.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115546},
doi = {10.1016/j.jconrel.2026.115546},
pmid = {43025506},
issn = {1873-4995},
abstract = {Oral protein delivery is hindered by gastrointestinal degradation and poor mucosal bioavailability. Engineered probiotics offer a promising strategy for oral protein delivery, but their therapeutic efficacy is often limited by insufficient payload expression and low secretion efficiency. Here, we present a living oral platform that integrates high-yield protein biosynthesis with on-demand intestinal release. By gene manipulation and FLAG tagging, we dramatically upregulate constitutive expression of GP532 in probiotic Escherichia coli Nissle 1917 (EcN), while installing an arabinose-inducible autolytic switch for efficient intracellular payload release. A dual-layer coating of polydopamine (PDA) and polyethylene glycol (PEG) confers acid resistance and mucus penetration, while allowing arabinose to permeate and blocking digestive enzymes. Upon single oral gavage in a murine model of radiation enteritis, our formulation achieves therapeutic efficacy fully equivalent to systemic injection of GP532 in mitigating intestinal injury. Critically, unlike injectable biologics, this living platform promotes the restoration of gut microbial community structure and beneficial taxa, a unique benefit unattainable by parenteral administration, while the engineered strain is completely cleared within 24 h. By synergizing genetic circuit engineering, surface chemical modification, and in situ luminal release, this work establishes a single-dose, orally effective alternative to injectable protein therapy, offering a transformative strategy for the prevention of radiation enteritis with the added benefit of microbiome maintenance.},
}

@article {pmid43025638,
year = {2026},
author = {Copes, J and Godeaux, E and Yan, S},
title = {Chronic ethanol feeding drives gut microbiome remodeling and influences cholestatic liver injury in mice.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.10.012},
pmid = {43025638},
issn = {1525-2191},
abstract = {Alcohol-associated liver disease (ALD) is a major cause of liver-related mortality worldwide and encompasses steatosis, cirrhosis, and alcohol-associated hepatitis (AH). AH is frequently accompanied by cholestasis, characterized by impaired bile flow and disrupted bile acid homeostasis. Although gut microbiome (GM) dysbiosis has been linked to ALD progression and cholestatic injury, its functional role in alcohol-associated cholestasis remains unclear. Mice were subjected to chronic ethanol-feeding (EF) or pair-feeding (PF) for 4 weeks. Fecal samples collected at 10 days and 4 weeks underwent shotgun metagenomic sequencing. To assess the functional impact of microbiome alterations, cecal contents from male mice after 4 weeks of EF or PF were used for fecal microbiota transplantation (FMT). Recipient mice received antibiotics during acclimatization, followed by 10 days of EF and FMT every other day. Forty-eight hours before sacrifice, mice were challenged with α-naphthylisothiocyanate (ANIT; 25 mg/kg) to induce cholestatic liver injury. Liver injury, cholestasis, and inflammation were evaluated biochemically and histologically. EF induced progressive GM remodeling, whereas PF did not. Unexpectedly, FMT from PF donors aggravated ANIT-promoted liver injury, cholestasis, and hepatic inflammation in EF recipients of both sexes. In contrast, FMT from EF donors did not significantly alter injury compared with non-FMT controls. These findings suggest that GM derived from PF and chronic EF mice differentially influence susceptibility to cholestatic liver injury in EF recipients.},
}

@article {pmid43025758,
year = {2026},
author = {Tyc, O and Arif, S and Uschner, FE and Jung, N and Gu, W and Ortiz, C and Klein, S and Zarei, S and Torres, S and Landvogt, N and Pedersen, KJ and Kew, C and Chen, W and Rooney, M and Arif, H and Castelli, F and Pons, N and Windbergs, M and Bruns, T and von Bergen, M and Garbeva, P and Zweers, H and Đikic, I and Ehrlich, D and Junot, C and Lelouvier, B and Trebicka, J and Schierwagen, R},
title = {Translocation of the environmental bacterium Aquitalea magnusonii promotes systemic inflammation and liver fibrosis in chronic liver disease.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2026.10.036},
pmid = {43025758},
issn = {1600-0641},
abstract = {BACKGROUND & AIMS: Impaired mucosal barrier integrity facilitates translocation of the gut microbiome into the circulation and the liver, thereby exacerbating the severity of chronic liver diseases (CLD). This study aimed to investigate the pathogenic role of non-commensal environmental bacteria, specifically Aquitalea magnusonii in CLD progression by assessing its ability to cross the intestinal barrier and induce systemic inflammation and liver fibrosis.

METHODS: Using an integrated translational framework, patient blood analyses were combined with multi-omics profiling, human intestinal epithelial models, peripheral blood mononuclear cells (PBMC), hepatic stellate cells (HSC), monocytes, and alcoholic (ALD) and metabolic dysfunction-associated (MASLD) models to evaluate the translocation, virulence, inflammatory and fibrotic potential of A. magnusonii in CLD.

RESULTS: Non-commensal environmental bacteria, including Aquitalea spp. were detected in multiple organs in both ALD and MASLD models. Detection of Aquitalea DNA in patient samples and other non-commensal environmental bacteria in tap water suggested potential aquatic reservoirs. A. magnusonii produced 12 acute-on-chronic liver failure (ACLF) associated metabolites and its outer membrane vesicles (OMV) were enriched in virulence-related proteins, supporting roles in adhesion, invasion, and immune activation. In addition, gavage with A. magnusonii led to a substantial dysbiotic shift in the gut microbiome. Mechanistically, the cell-free supernatant of A. magnusonii culture activated TLR2- and TLR4-dependent pro-inflammatory signaling pathways. Exposure to A. magnusonii or its pathogen-associated molecular patterns (PAMPs) significantly increased inflammation and fibrosis in vitro and in vivo.

CONCLUSION: Non-commensal environmental bacteria, in the example of A. magnusonii, can translocate across the intestinal barrier and promote liver inflammation and fibrogenesis via metabolite production, virulence-associated OMV, and innate immune activation.

IMPACT AND IMPLICATIONS: This study highlights an underrecognized role of non-commensal environmental bacteria in chronic liver disease. Beyond gut commensals, detection of non-commensal environmental microbes such as Aquitalea was associated with markers of more advanced liver disease, while experimental studies of A. magnusonii support biological plausibility for a potential contributory role. These findings highlight the importance of considering environmental reservoirs and non-commensal pathogens in microbial contributions to CLD pathogenesis.},
}

@article {pmid43025765,
year = {2026},
author = {Murphy, SM and Ege, MJ},
title = {The farm effect on asthma and allergies - Thirty years of research.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2026.10.027},
pmid = {43025765},
issn = {1097-6825},
abstract = {The 'farm effect' describes a strong asthma- and allergy-protective signal by farm exposure, which is surprisingly consistent across the globe. Representing a more traditional lifestyle, the farm environment appears to be a reminiscent of the environmental exposure humankind experienced since the neolithic. The farm environment is characterized by a high microbial load and diversity, which seem essential for adequate immune maturation. The aim of this review article is to delineate how research into the farm effect evolved from classical epidemiology over biomarker research, microbiome sequencing, and multi-omics analyses to emerging prevention strategies. We explore how the farm effect and the various versions of the hygiene hypothesis are closely intertwined with each simultaneously contributing the development of the other. We follow the development of our understanding of the mechanisms underpinning the farm effect, focusing on the two most consistent exposures, namely microbial exposure in animal sheds and consumption of unprocessed cow's milk. The decades of research into the farm effect represent true translational work: Moving from observation to intervention, with the advent of new therapeutic interventions on the horizon, now is the time to look back at how it all started, how our understanding has evolved over time and what this might mean for the future.},
}

@article {pmid43025989,
year = {2026},
author = {Schöler, D and Hsu, CL and Miwa, T and Brol, MJ and Freund, L and Lang, S and Fouts, DE and , and Stärkel, P and Schnabl, B},
title = {Altered IgA-associated gut microbiota and serum IgA are associated with disease severity in alcohol-associated liver disease.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2026-339201},
pmid = {43025989},
issn = {1468-3288},
}

@article {pmid43026054,
year = {2026},
author = {Flaig, ML and Hardwick, MMJ and Burmølle, M and Alker, ATP},
title = {How to train your microbe: editing environmental bacteria.},
journal = {Trends in microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tim.2026.10.007},
pmid = {43026054},
issn = {1878-4380},
abstract = {Genome editing is an essential tool in microbiology, enabling researchers to assess gene function, link genotype to phenotype, and design microbes with specific features. Most tools have been developed in model bacteria, and adapting them to environmental species remains time- and resource-intensive. This review provides a framework for engineering environmental bacteria, including assessment of genetic tractability, considerations for overcoming challenges in recalcitrant systems, and an overview of techniques with guidance on tool selection. We discuss the emerging field of microbiome editing, where genome modifications can be delivered to bacteria within complex microbial communities and hosts, opening new possibilities for mechanistic studies across diverse environments. These advances promise to shift functional microbiology from reductionist, isolate-based approaches toward contextually informed, mechanistic investigations.},
}

@article {pmid43026137,
year = {2026},
author = {Rich, S and Fawad, JA and Baldassano, RN and Zackular, JP and Pai, N},
title = {Microbial medicine in clinical pediatrics: evolving approaches to diagnosis and management.},
journal = {Current problems in pediatric and adolescent health care},
volume = {},
number = {},
pages = {102003},
doi = {10.1016/j.cppeds.2026.102003},
pmid = {43026137},
issn = {1538-3199},
abstract = {Our increasing understanding of the microbiome has revealed its critical role in immunity, metabolism, infectious disease susceptibility, and overall human health. Advances in the detection of microbial species using new sequencing technologies has led to the emergence of a new frontier in medicine. Integrating the microbiome with diagnostics and therapeutics has introduced the field of 'microbial medicine', representing a major translational advance in pediatric healthcare. The early-life microbiome is particularly important serving as a critical developmental window during which rapidly altering microbial communities can contribute to immune tolerance and confer disease risk. Factors that can shape the early-life microbial landscape include delivery mode, breastfeeding, diet, antibiotic exposure and geography. Disruptions in the microbiome have been linked to numerous pediatric diseases including necrotizing enterocolitis, inflammatory bowel disease, neonatal sepsis, allergic diseases, metabolic syndrome, neurodevelopmental disorders and psychiatric conditions. While early microbiome research has been largely correlational, growing mechanistic insights into host-microbe interactions have paved the way for the development of microbiome-targeted therapeutics. Promising approaches include prebiotics, probiotics, fecal microbiota transplantation, liver biotherapeutic products, genetically engineered microbes and microbiome-derived metabolites. Studies are however lacking in the pediatric population and therefore there is a growing need for a coordinated effort to increase access to microbiome-based therapeutics in children. Significant challenges include a lack of age-specific reference standards, understanding long-term safety, and standardizing available treatments. In this review we discuss the emergence of microbial medicine in pediatric care. We examine the current evidence evaluating the development of the microbiome, the factors that shape early-life microbial colonization and the use of microbial therapeutics in clinical practice. We highlight the challenges and opportunities associated with translating these discoveries into pediatric practice and suggest research priorities and infrastructure development required to establish microbial medicine as a mainstay in pediatric practice.},
}

@article {pmid43026253,
year = {2026},
author = {Edwards, LA and Edwards, JA and Dailey, Y},
title = {From penicillin to precision: reframing AMR in dentistry through time - past lessons, present risks, and future solutions.},
journal = {British dental journal},
volume = {241},
number = {9},
pages = {689-697},
doi = {10.1038/s41415-026-0173-y},
pmid = {43026253},
issn = {1476-5373},
mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *Penicillins/therapeutic use ; *Dentistry/trends ; *Antimicrobial Stewardship ; Risk Assessment ; Drug Resistance, Bacterial ; },
abstract = {Antimicrobial resistance (AMR) is a public health global threat projected to cause 10 million deaths annually by 2050 and a major health protection issue. Dentistry contributes approximately 10% of antibiotic prescriptions worldwide, often for conditions where antibiotics offer limited benefit. This article reframes AMR in dentistry through a historical, current, and future lens, integrating risk assessment principles, empirical prescribing trends, and precision strategies. We trace the trajectory from the penicillin era to modern stewardship challenges, examine the dental AMR burden and prescribing patterns using English Surveillance Programme for Antimicrobial Utilisation and Resistance 2023-2024 data, and explore innovative solutions including rapid diagnostics, microbiome restoration, and non-antibiotic therapies. Drawing on evolutionary insights from ancient microbiomes, we argue that AMR is not merely a clinical phenomenon, but a microbial ecological imbalance driven by industrialisation and antibiotic overuse. Future health protection strategies involving interdisciplinary working must combine stewardship with precision dentistry and microbial ecosystem restoration in a one-world setting to mitigate AMR risk while preserving microbial and host resilience. Public health plays an important role working with a range of other stakeholders/agencies in a multidisciplinary approach.},
}

Humans
*Anti-Bacterial Agents/therapeutic use
*Penicillins/therapeutic use
*Dentistry/trends
*Antimicrobial Stewardship
Risk Assessment
Drug Resistance, Bacterial

@article {pmid43026532,
year = {2026},
author = {Liu, Y and Lin, M and Luo, J and Yang, J and Yao, Z and Lin, D and Qiu, H and Zhang, Z and Huang, S and Zheng, E and Cai, G and Wu, Z and Liu, L and Wu, JJ},
title = {Integrating whole-genome sequencing and metagenomics improves phenotype prediction of fat deposition traits in pigs.},
journal = {Genetics, selection, evolution : GSE},
volume = {58},
number = {1},
pages = {},
pmid = {43026532},
issn = {1297-9686},
support = {2025B0202080002//Natural Science Foundation of Guangdong Province project/ ; 2025-XPY-01-002//Guangdong Provincial Special Finance Project for Seed Industry Revitalization Action/ ; NYQN2025004//Guangdong Special Support Program/ ; 2019BT02N630//Local Innovative and Research Teams Project of Guangdong Province/ ; 32502844//National Natural Science Foundation of China/ ; GZB20230230//the Postdoctoral Fellowship Program of CPSF/ ; GZB20250817//the Postdoctoral Fellowship Program of CPSF/ ; },
mesh = {Animals ; *Metagenomics/methods ; Phenotype ; *Whole Genome Sequencing/methods ; Swine/genetics ; *Gastrointestinal Microbiome/genetics ; Polymorphism, Single Nucleotide ; *Adipose Tissue ; Genotype ; },
abstract = {BACKGROUND: Fat deposition is a key economic trait affecting production efficiency and carcass quality in pigs and is influenced by both genetic and environmental factors. Although increasing evidence indicates that the gut microbiome contributes to host phenotypic variation, current genomic evaluation and prediction models largely rely on host genotype information and rarely account for microbiome effects. This study aimed to quantify the contribution of the gut microbiome to fat deposition traits and to evaluate whether incorporating microbiome information could improve phenotypic prediction in pigs.

RESULTS: We collected phenotypic characteristics of six fat deposition traits including the shoulder backfat thickness, the 6th-7th rib backfat thickness, the last rib backfat thickness, waist backfat thickness, the 3rd-4th last rib backfat thickness, and the average backfat thickness from 478 Duroc × Landrace × Yorkshire pigs. Using whole-genome resequencing and metagenomic sequencing, we identified 21 million single nucleotide variants and quantified the abundances of 20,336 gut microbial species across 478 pigs. Distinct fecal microbial community structures were observed between pigs with high- and low-fat deposition, and 27 bacterial species were identified as potential biomarkers associated with fat deposition. Microbiability estimates for the six backfat thickness traits ranged from 0.17 to 0.44, indicating that the gut microbiome accounted for a considerable proportion of phenotypic variance beyond host genetic contributions. In contrast, the interaction effects between the host genome and gut microbiome accounted for only a negligible proportion of phenotypic variance across the six traits. Incorporating overall microbiome information into genomic prediction models resulted in mean phenotypic predictive abilities ranging from 0.082 to 0.292, representing increases in predictive ability of 0.023 to 0.084 across traits and reductions in the mean squared error of prediction of 0.001 to 0.009 compared with the additive genetic model.

CONCLUSIONS: Our findings demonstrate that the gut microbiome makes a substantial contribution to variation in fat deposition traits in pigs. Integrating host whole-genome resequencing and gut metagenomic information yielded modest absolute gains in phenotypic predictive ability, suggesting that the gut microbiome may provide complementary information for prediction models of complex traits in pigs.},
}

Animals
*Metagenomics/methods
Phenotype
*Whole Genome Sequencing/methods
Swine/genetics
*Gastrointestinal Microbiome/genetics
Polymorphism, Single Nucleotide
*Adipose Tissue
Genotype

@article {pmid43026595,
year = {2026},
author = {Loganathachetti, DS and Michalzik, B and Sandoval, MM and Zerhusen, P and Richter, R and Engelmann, RA and Künne, T and Wirth, C and Küsel, K and Herrmann, M},
title = {Traversing the canopy: phenology-driven changes and within-canopy transport shape the phyllosphere microbiome in a temperate floodplain hardwood forest.},
journal = {Environmental microbiome},
volume = {21},
number = {1},
pages = {},
pmid = {43026595},
issn = {2524-6372},
abstract = {Phyllosphere microbiomes are subject to microbial import from various sources and undergo substantial changes during phenological changes of plants. However, especially for forest canopies, these processes are still poorly understood. We disentangled the controls of phenology-driven changes versus tree species identity on the phyllosphere microbiome in a temperate floodplain forest and assessed the role of transport processes in shaping distribution patterns within the canopy. Leveraging the infrastructure of the Leipzig canopy crane (Central Germany), we followed bacterial community composition and rainwater-mediated bacterial transport for oak (Quercus robur L.), ash (Fraxinus excelsior L.) and linden (Tilia cordata MILL) across early (May), mid (July) and late (October) phenological stages. These stages explained 23% of phyllosphere bacterial community variation, followed by tree species identity (13%) and canopy position (2%). Phyllosphere bacterial community assembly was mostly driven by dispersal limitation at the early phenological stage while communities became more homogeneous and functionally redundant during mid and late phenological stages, along with a strong decline of plant pathogens and increasing potential for microbially mediated biocontrol mechanisms. Throughfall-mediated transport of bacteria increased substantially from March to May, indicating the strong influence of wash-off effects from the emerging foliage. Our findings demonstrate that in temperate forests, phenology-driven effects on the phyllosphere microbiome exceed tree species' specific effects. Extent and selectivity of throughfall-mediated mobilization of microbes adds another layer of complexity to the spatial heterogeneity of microbial communities in tree crowns.},
}

@article {pmid43026600,
year = {2026},
author = {Kong, L and Zhang, X and Ding, L and Liu, L and Wang, J and Zhang, Z and Tu, H and Li, J and Chen, T},
title = {ILA-producing Lacticaseibacillus paracasei NCU-21 exerts anti-acute myeloid leukemia effects by inhibiting the PI3K-AKT pathway.},
journal = {Genome biology},
volume = {27},
number = {1},
pages = {},
pmid = {43026600},
issn = {1474-760X},
support = {81760033//National Natural Science Foundation of China/ ; 20223BBG71006//Key Research and Development Program of Jiangxi Province/ ; },
mesh = {Animals ; *Leukemia, Myeloid, Acute/metabolism/therapy/drug therapy/microbiology/pathology ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/drug effects ; Mice ; *Lacticaseibacillus paracasei/metabolism ; *Probiotics/therapeutic use/pharmacology ; Humans ; Gastrointestinal Microbiome/drug effects ; Cytarabine/pharmacology/therapeutic use ; },
abstract = {BACKGROUND: Cytarabine (Ara-C) remains the cornerstone of induction therapy for acute myeloid leukemia (AML). However, its overall clinical efficacy is suboptimal, and the regimen is frequently accompanied by severe disruption of intestinal homeostasis. Consequently, identifying novel adjunctive therapies to improve treatment outcomes represents a critical clinical need.

RESULTS: Gut microbiome profiling in AML mouse models reveals that Ara-C treatment significantly depletes Lactobacillus abundance. Through a probiotic intervention model, we demonstrate that administration of Lacticaseibacillus paracasei NCU-21 reduces leukemic burden, as well as size and weight of the spleen (p < 0.05). Mechanistically, L. paracasei NCU-21 restores microbial homeostasis, upregulates tight junction proteins (p < 0.05), and suppresses the lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4) pathway (p < 0.01), thereby attenuating systemic pro-inflammatory cytokine levels. Subsequent metabolomics confirms that indole-3-lactic acid (ILA) is the primary functional metabolite of L. paracasei NCU-21. In vivo administration of ILA recapitulates the anti-AML effects of the probiotic, and in vitro assays confirm that ILA directly induces AML cell apoptosis (p < 0.001) by suppressing the PI3K-AKT pathway.

CONCLUSIONS: This work demonstrates that L. paracasei NCU-21 mitigates AML progression via the production of ILA, supporting its potential as an adjunct therapy.},
}

Animals
*Leukemia, Myeloid, Acute/metabolism/therapy/drug therapy/microbiology/pathology
*Proto-Oncogene Proteins c-akt/metabolism
*Phosphatidylinositol 3-Kinases/metabolism
Signal Transduction/drug effects
Mice
*Lacticaseibacillus paracasei/metabolism
*Probiotics/therapeutic use/pharmacology
Humans
Gastrointestinal Microbiome/drug effects
Cytarabine/pharmacology/therapeutic use

@article {pmid43026629,
year = {2026},
author = {Boer, MD and Peets, P and van Eijnatten, AL and Nelson, CE and do Canto Brum de Menezes Pena, MM and Karancz, S and Humphreys, MP and van Duyl, FC and Meesters, EH and Snoek, BL and Melkonian, C and Haas, AF and Dutilh, BE},
title = {A specialized microbiome enriched in nitrification and halogen cycling potential resolved from multi-omics investigation of a Caribbean suboxic and acidic marine sinkhole.},
journal = {Microbiome},
volume = {14},
number = {1},
pages = {},
pmid = {43026629},
issn = {2049-2618},
mesh = {*Nitrification ; *Microbiota ; Multiomics ; Metagenomics/methods ; *Bacteria/classification/metabolism/genetics/isolation & purification ; *Halogens/metabolism ; *Lakes/microbiology/chemistry ; Metabolomics ; Hydrogen-Ion Concentration ; },
abstract = {BACKGROUND: The Luymes Sinkholes, located on the Luymes Bank northwest of Saba, represent a unique marine environment characterized by distinct biogeochemical gradients. Most noticeable is an acidic (pH ≈ 6.25) and suboxic (O2 < 60 µmol/kg) submerged 'lake' at ~ 220 m depth exhibiting extreme deviations from standard oceanographic patterns, including elevated inorganic carbon, nitrate, and phosphate, and a lower temperature (20.3 ºC vs 26.4 ºC). To determine how the microbiome within the submerged acid lake adapted to these unique conditions, we collected 59 coupled samples of size-filtered (0.22 µm) planktonic microbes for shotgun metagenomics and solid-phase extracted dissolved organic matter for untargeted metabolomics from 21 stations at depths ranging from 2 to 600 m during a 10-day research cruise in December 2019.

RESULTS: We identified a distinct microbial community within the submerged acid lake different from the non-acidic sinkholes, with increased abundances of Nitrospinota, Thermoproteota, Planctomycetota, and Actinobacteriota. We also found three enriched classes of dissolved compounds within the submerged acid lake: (1) large, (2) low-polarity, and (3) halogenated metabolites, including iodides and halobenzoic acids. Correlations between microbial taxa and metabolite classes show potential links between nitrifying archaea and halogenated compound cycling. We further supported these findings using the functional annotation of metagenome-assembled genomes (MAGs) and protein clusters showing enrichment of nitrification and halogen cycling genes, suggesting the presence of specialized degradation and biosynthetic pathways, directly connecting microbial metabolism to the observed geochemical conditions.

CONCLUSION: These findings demonstrate that the submerged acid lake contains specific microbially driven biogeochemical processes under acidified and low-oxygen conditions, providing a natural model for future extreme ocean acidification scenarios. With this multi‑omics approach, we were able to connect the microbial metabolism with this unique environment, thereby expanding our understanding of how both are interconnected. Video Abstract.},
}

*Nitrification
*Microbiota
Multiomics
Metagenomics/methods
*Bacteria/classification/metabolism/genetics/isolation & purification
*Halogens/metabolism
*Lakes/microbiology/chemistry
Metabolomics
Hydrogen-Ion Concentration

@article {pmid43026637,
year = {2026},
author = {Seethaler, B and Basrai, M and Delzenne, NM and Walter, J and Nguyen, NK and Bischoff, SC},
title = {Correction: Baseline gut microbiome and metabolome profiles predict weight loss after a structured lifestyle intervention.},
journal = {Microbiome},
volume = {14},
number = {1},
pages = {},
pmid = {43026637},
issn = {2049-2618},
}

@article {pmid43026748,
year = {2026},
author = {Yang, X and Ge, X and Gong, S and Zhu, T and Ni, C and Ma, R and Tao, Q},
title = {Fecal Microbiota Transplantation in Colorectal Cancer: From Immune Regulation to Immunotherapy.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026748},
issn = {2072-6694},
support = {2026-YRDFHI-141//Shanghai YRD Foundation for Innovation in Health Industry/ ; },
abstract = {The gut microbiome influences colorectal cancer (CRC) progression and responses to immune checkpoint inhibitors (ICIs), with immunotherapy resistance remaining a major challenge in microsatellite-stable/mismatch repair-proficient (MSS/pMMR) CRC. This review examines the mechanisms and translational potential of fecal microbiota transplantation (FMT) in CRC immunotherapy, focusing on the interplay among microbial functions, metabolic alterations, and immune microenvironment remodeling. Current evidence suggests that FMT may influence antitumor immunity beyond restoring microbial diversity by transferring functionally relevant microbial communities, metabolic profiles, and immunomodulatory signals. These changes may affect antigen presentation, inflammatory signaling, T-cell activity, and myeloid-cell states, thereby shaping the tumor immune microenvironment and potentially modulating responses to PD-1/PD-L1 blockade. However, the clinical efficacy of FMT in CRC, the determinants of successful microbial engraftment, and the mechanisms linking donor-derived microbial functions to therapeutic outcomes remain incompletely understood. Integrating defined microbial consortia, metabolite-based interventions, and multi-omics-guided patient stratification may help advance FMT toward mechanism-driven precision microbiome therapy and inform strategies to improve CRC immunotherapy outcomes.},
}

@article {pmid43026751,
year = {2026},
author = {Sidhom, F and Karabiber, E and ElBeblawy, R and Babagiray, A and Yacoub, T and El-Rayes, B and Akce, M},
title = {Immune and Circulating Biomarkers in Hepatocellular Carcinoma: Prognostic and Predictive Relevance for Immunotherapy.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026751},
issn = {2072-6694},
abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Immune checkpoint inhibitor (ICI)-based combinations have become the standard first-line systemic therapy, yet objective response rates remain modest (20-36%), and no HCC-specific immune biomarker has been validated to guide selection among standard ICI-based regimens. This review examines the prognostic and exploratory treatment-response associations of potential immune biomarkers in HCC, including markers within the tumor microenvironment (TME) and peripheral blood. A narrative review was conducted evaluating PD-L1 and soluble PD-L1, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), including machine learning-based assessment, gene expression profiles and tumor-intrinsic pathway alterations, long non-coding RNAs, inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, alpha-fetoprotein), gut microbiota, and liquid biopsy analytes (circulating tumor DNA, circulating tumor cells, cell-free DNA). PD-L1 expression shows prognostic associations and inconsistent associations with ICI outcomes; inter-assay heterogeneity further limits its use, and routine PD-L1 testing is not recommended by current guidelines. TMB is generally low in HCC, with inconsistent associations with ICI response. High CD8[+] TIL density is associated with improved survival after resection and favorable outcomes in exploratory ICI-treated cohorts, without validated treatment-selective utility. Inflammatory gene signatures and WNT/β-catenin pathway activation are associated with ICI outcomes. Gut microbiome features have shown exploratory associations with anti-PD-1 outcomes, with limited consistency across small datasets. Liquid biopsy markers, particularly ctDNA, show promise for recurrence prediction and treatment monitoring but lack assay standardization. Multiple immune biomarkers demonstrate prognostic value in HCC, and pre-existing immunity characterized by high CD8[+] T-cell infiltration and inflammatory gene signatures is associated with improved ICI-based therapy outcomes in exploratory studies. However, these exploratory markers have not been validated for routine selection among HCC regimens. Future directions include prospective validation of composite biomarker panels, standardization of assessment methodologies, and integration of artificial intelligence for TME characterization.},
}

@article {pmid43026775,
year = {2026},
author = {Wrzosek, K and Koba, A and Bakalczuk, P and Oziębło, J and Michno, K and Pająk, W and Kleinrok, J and Korolczuk, A and Trojanowska, D and Forma, A},
title = {The Changing Global Epidemiology of Early-Onset Colorectal Cancer: Incidence Trends, Modifiable Risk Factors, and Future Burden Projections.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026775},
issn = {2072-6694},
abstract = {Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before age 50, has become an increasing global public health concern. Incidence rates have risen among younger adults in many countries, despite stable or declining rates in older populations. This review examines global EOCRC epidemiology, potentially modifiable risk factors, and projected future disease burden. Evidence from international cancer databases, population-based registries, and observational studies is synthesised, considering differences by age, sex, geographic region, and tumour location. Key risk factors include obesity, metabolic dysfunction, dietary patterns, physical inactivity, alcohol consumption, tobacco use, antibiotic exposure, and gut microbiome alterations. The review also evaluates temporal trends and projections of incidence, prevalence, and mortality. Although increasing incidence may reflect changing lifestyles, metabolic health, environmental exposures, and other early-life risk factors, their relative contributions remain incompletely understood. Improved understanding of EOCRC epidemiology and future burden may help identify high-risk populations, guide targeted prevention strategies, inform public health policy, and support discussions on earlier colorectal cancer detection and screening.},
}

@article {pmid43026802,
year = {2026},
author = {Mihalj, M and Mioč, NF and Sabljić, I and Čeprnja, ZŠ and Tokić, S and Buljan, M},
title = {Immunosenescence and Inflammaging in the Pathogenesis of Non-Melanoma Skin Cancer.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026802},
issn = {2072-6694},
support = {IP13-2024//Faculty of Medicine Osijek/ ; NPOO 581-UNIOS-83//University Josip Juraj Strossmayer of Osijek/ ; IP1-2026//Faculty of Medicine Osijek/ ; },
abstract = {Non-melanoma skin cancer (NMSC) is the most frequently diagnosed malignancy worldwide, and its incidence rises disproportionately with age. While cumulative ultraviolet (UV) exposure is the dominant recognised risk factor, it does not fully account for the steep age-associated increase in NMSC, suggesting that additional, underrecognised mechanisms operate in older skin. This review synthesises evidence that immune senescence (the age-related remodelling of innate and adaptive immunity) is a central and partly modifiable driver of NMSC aetiopathogenesis. We first outline the classical risk factors and the epidemiological and economic burden of NMSC, and revisit the proposal to regard recurrent NMSC as a chronic disease. We then examine four interlocking, age-associated processes: the accumulation of senescent cells and their pro-inflammatory secretory phenotype ("inflammaging") in the skin microenvironment; UV-induced suppression of cutaneous immune function; age-related dysbiosis of the skin microbiome and its impact on antitumour immunity; and the systemic decline of T-cell-mediated tumour immunosurveillance. We integrate these processes into a framework in which immune senescence contributes to the progression of accumulated cutaneous damage to overt malignancy, and consider the implications for prevention (including senotherapeutics, microbiome modulation, and immune-stratified surveillance) that extend beyond UV-directed measures alone.},
}

@article {pmid43026843,
year = {2026},
author = {El-Mosalamy, B and Balaha, HM and El-Moursi, S and Gondim, D and Lweesy, K and Yousaf, J and Ghazal, M and El-Baz, A},
title = {Artificial Intelligence for Colorectal Cancer Diagnosis: A Comprehensive Survey of Modalities, Frameworks, and Clinical Tasks.},
journal = {Cancers},
volume = {18},
number = {21},
pages = {},
pmid = {43026843},
issn = {2072-6694},
abstract = {The diagnosis of colorectal cancer encompasses nine complementary modalities: stool-based screening, blood-based biomarkers, cross-sectional imaging, endoscopic evaluation, histopathology, liquid biopsy, molecular and genetic profiling, microbiome analysis, and nanotechnology-based diagnostics. This narrative review synthesizes 160 references spanning seven task-specific artificial intelligence domains, including computer-aided detection, optical diagnosis, invasion depth prediction, computational pathology and radiogenomics, metastasis forecasting, neoadjuvant treatment response prediction, and surgical workflow analysis. We propose a conceptual multimodal pipeline comprising data ingestion, preprocessing and harmonization, feature representation, multimodal fusion, forecasting, explainability, and validation. A structured evidence grading framework classifies each clinical task by evidence level, consistency, and clinical readiness. We further catalog public datasets, challenge benchmarks, and five reporting standards: TRIPOD-AI, CONSORT-AI, SPIRIT-AI, DECIDE-AI, and CLAIM. Computer-aided detection and optical diagnosis demonstrate the highest maturity with Level 1 evidence from randomized controlled trials, while computational pathology, radiogenomics, and metastasis prediction remain at Level 2 with retrospective validation (internal or external). Microbiome screening, nanotechnology diagnostics, and surgical phase recognition are exploratory. The principal barriers to clinical adoption are domain shift, data scarcity, calibration, prospective validation, and workflow integration. We conclude that clinically useful artificial intelligence requires robust external validation, uncertainty quantification, explainable outputs, standardized reporting, and a structured translational pathway from retrospective evidence through regulatory clearance to post-deployment monitoring.},
}

@article {pmid43026940,
year = {2026},
author = {Zhang, Y and Sun, Y and Zhai, X and Zhou, J and Liu, L},
title = {Temporal Transcriptomic Responses of Turbinaria peltata to Repeated Marine Heatwaves and Recovery Cycles.},
journal = {Biology},
volume = {15},
number = {21},
pages = {},
pmid = {43026940},
issn = {2079-7737},
support = {2022YFD2401302//National Key R&D Project of China/ ; 060302022401//Program for Scientific Research Start-up Funds of Guangdong Ocean University/ ; },
abstract = {Marine heatwaves (MHWs) are escalating threats to coral reef ecosystems, yet the host transcriptomic mechanisms underlying acclimatization to repeated thermal stress remain poorly understood. Using de novo RNA sequencing, we tracked the temporal transcriptomic responses of the scleractinian coral Turbinaria peltata across two consecutive MHW-recovery cycles. The second heatwave elicited fewer differentially expressed genes (DEGs) than the first (279 vs. 379), whereas the second recovery phase showed the largest DEG set (399). Functionally, the first heatwave triggered acute stress defense and signal suppression, while the first recovery engaged extracellular matrix remodeling and calcium-mediated tissue repair, indicating incomplete restoration. The largest DEG set during the second recovery indicates that recurrent thermal stress imposes cumulative physiological costs demanding more extensive molecular reorganization-spanning metabolic reprogramming, mTOR and Wnt signaling, and sustained oxidative-stress management. Together with prior physiological and microbiome evidence in this species, our results support a model in which repeated heat exposure progressively shifts the coral host from acute shock defense responses toward compensatory metabolism and structural repair. Recovery thus emerges as an active but increasingly costly molecular adjustment under recurrent MHW regimes. These findings identify candidate molecular markers for evaluating coral resilience under intensifying MHW regimes.},
}

@article {pmid43026972,
year = {2026},
author = {Ma, P and Ruan, H and Zhang, H},
title = {A Multilevel Perspective on the Skin: Skin Architecture, Microbial Communities, Intrinsic Metabolites, and Emerging AI-Enabled Applications.},
journal = {Biology},
volume = {15},
number = {21},
pages = {},
pmid = {43026972},
issn = {2079-7737},
abstract = {The skin is the largest organ of the human body and harbors a diverse microbial community that constitutes a complex ecosystem. Despite advances in next-generation sequencing (NGS) that have greatly facilitated the characterization of skin microbiota composition, a critical gap remains in understanding how intrinsic metabolites mediate host-microbe interactions and maintain microecological homeostasis. This review synthesizes current knowledge across interconnected layers of the skin ecosystem, including architecture, microbial communities, metabolites, and computational analytics. The skin's structural features create spatially heterogeneous microenvironments that dictate microbial colonization patterns, while microbial communities have evolved adaptive strategies to exploit distinct metabolic niches. Intrinsic metabolites, encompassing lipids, proteins/peptides, ions, vitamins, and carbohydrates, constitute the chemical language through which host and microbes reciprocally communicate. The complexity of these interactions poses challenges for traditional analytical approaches, yet artificial intelligence is transforming the field by enabling progressive deepening of understanding, from predicting microbial functional potential to decoding the skin microbiome as a carrier of biological information. This multilevel framework provides a foundation for future investigations and may inform the development of personalized strategies for skin health management.},
}

@article {pmid43027058,
year = {2026},
author = {Mahajna, A and Gacesa, R and Keesman, KJ and Euverink, GW and Jayawardhana, B},
title = {DIVE: Diversity-Informed Valuation of Ecosystem Functioning.},
journal = {Biology},
volume = {15},
number = {21},
pages = {},
pmid = {43027058},
issn = {2079-7737},
support = {//Wetsus, European Centre of Excellence for Sustainable Water Technology/ ; },
abstract = {Meta-omics datasets are inherently high-dimensional, complicating their interpretation and limiting their application to ecological and ecosystem-level analyses. We present DIVE (Diversity-Informed Valuation of Ecosystem Functioning), a structured and reproducible workflow that aggregates high-dimensional meta-omics data into ecologically meaningful community-level descriptors for investigating biodiversity-ecosystem functioning (BEF) relationships. Rather than introducing new diversity metrics or statistical estimators, DIVE integrates established alpha-diversity measures with sampling-design-aware temporal association analysis into a unified framework for relating microbial community structure to ecosystem function. The workflow is demonstrated using a multi-year metatranscriptomics dataset from a full-scale activated sludge wastewater treatment plant. DIVE identified a coherent temporal pattern approximately 23 days before ecosystem-functioning measurements, with richness-, diversity-, and evenness-related descriptors showing positive associations and dominance-related descriptors showing associations in the opposite direction. These relationships are interpreted as exploratory biodiversity-function associations rather than evidence of causation or validated prediction. By formalizing the integration of established analytical approaches into a temporally explicit workflow, DIVE supports reproducible and ecologically interpretable BEF analyses of longitudinal meta-omics data and prioritization of candidate relationships for further mechanistic investigation.},
}

@article {pmid43027068,
year = {2026},
author = {Saikhwan, N and Faroongsarng, D and Ruangpanit, Y and Thodsapol, A and Rassmidatta, K and Goossens, T and Vieco-Saiz, N and Prévéraud, DP and Theapparat, Y},
title = {Combined Dietary Supplementation with Bacillus subtilis DSM 29784 and a Phytogenic Blend Modulates the Microbiome-Gut-Bone Axis in Broiler Chickens.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027068},
issn = {2076-2615},
support = {OTR2568-007//Prince of Songkla University/ ; },
abstract = {The microbiome-gut-bone axis may influence skeletal physiology in fast-growing broilers. This study evaluated dietary Bacillus subtilis DSM 29784 combined with a phytogenic blend (BsP) in 560 male Ross 308 broilers assigned to control or BsP diets (eight pens/treatment; 35 birds/pen) for 42 days. One clinically normal bird per pen was sampled on days 21, 35, and 42. BsP increased final body weight and cumulative gain and reduced the overall feed conversion ratio (p < 0.05). Intestinal barrier-associated gene expression increased, several ileal inflammatory marker transcripts decreased, and mineral-handling-related gene expression and serum/femoral mineral concentrations were higher at selected ages. Cecal 16S rRNA gene profiles showed differences in diversity and taxonomic composition. PICRUSt2 identified differences in predicted microbial functional potential, not measured pathway activity or metabolite production. Femoral inflammatory and osteogenic gene expression responses varied with age. Exploratory networks summarized microbiome-gut-bone associations at days 21, 35, and 42 without establishing causality or within-bird temporal change. BsP was associated with improved growth and altered intestinal and bone-related indicators, but clinical BCO prevention was not established. Future factorial studies should include direct bone quality measurements, standardized clinical and lesion assessments, and targeted microbial metabolite measurements.},
}

@article {pmid43027085,
year = {2026},
author = {Yu, J and Li, P and Guo, Q and Li, Q and Xu, C and Tran, NT and Chen, X and Yang, W and Sun, J and Li, S and Zhang, M},
title = {Gut Microbiota Alterations and Intestinal Pathology in Healthy, Moribund, and Recently Dead Mastacembelus Armatus from a Pond Aquaculture System.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027085},
issn = {2076-2615},
support = {2024A1515011613//Science Foundation of Guangdong Province/ ; 2025GXNSFAA069705//Natural Science Foundation of Guangxi Province/ ; },
abstract = {Spiny eel (Mastacembelus armatus) pond aquaculture suffers from recurrent nonspecific mortality, yet the associations between gut-microbiota shifts, host histological alterations, and fish physiological status, as well as the potential roles of sediment microbiota, remain unclear. In this study, we collected healthy (H), moribund (M), and recently dead (D) fish, as well as pond sediment (S), and performed histopathological examination and 16S rRNA amplicon sequencing combined with FEAST source-tracking analysis. Histology revealed severe intestinal villus atrophy, epithelial shedding, and extensive hepatic vacuolation in M fish. Results of 16S rRNA sequencing revealed a significant decrease in the alpha diversity (Chao1) of gut microbial richness in M and D groups, compared with healthy (H) (p < 0.05). Healthy guts were dominated by Proteobacteria and the keystone genus Cetobacterium (about 40% relative abundance). In M/D, Cetobacterium nearly disappeared, while Firmicutes and Fusobacteriota became predominant, with potentially opportunistic taxa (Fusobacterium, Clostridiaceae) showing markedly higher relative abundance. Beta-diversity and LEfSe analyses showed overlapping microbial communities between M and D fish, which were distinct from those of healthy (H) fish. FEAST modeling output showed that the conditionally estimated sediment-derived proportion increased from approximately 28% in healthy (H) to ~99% in M fish. Functional profiles predicted by PICRUSt2 shifted from oxidative phosphorylation toward peptidoglycan biosynthesis and peptidase-related functional potentials. Collectively, our results demonstrate strong associations between gut-microbiota disruption, intestinal barrier impairment, and fish physiological decline. We observed associations between damaged intestinal barrier status and increased sediment-attributed fractions of potentially opportunistic microbes within the gut microbiota.},
}

@article {pmid43027115,
year = {2026},
author = {Chen, K and Dong, X and He, H and Huang, Y and Su, Y},
title = {Indole-3-Lactic Acid Modulates Feeding Behavior and Appetite-Related Signals in Weaned Piglets.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027115},
issn = {2076-2615},
abstract = {Gut microbiota-derived metabolites act as important mediators linking the gut microbiome with host physiological functions and participate in the regulation of metabolic homeostasis and behavior. However, whether the tryptophan metabolite indole-3-lactic acid (ILA) regulates feeding behavior in piglets and its potential central regulatory mechanisms remain unclear. In this study, 12 weaned piglets were used as a model to investigate the effects of ILA on feeding behavior regulation. The results showed that ILA supplementation did not significantly affect growth performance (p > 0.05), although final body weight, average daily gain, and average daily feed intake were numerically higher in the ILA group than in the control group. ILA also altered feeding behavior patterns, characterized by reduced daily feeding frequency (p < 0.05) and increased feeding rate (p = 0.053). Furthermore, ILA significantly increased serum concentrations of several appetite-related gastrointestinal hormones, including glucagon-like peptide-1, peptide YY, ghrelin, and cholecystokinin, and modified serum lipid metabolism-related parameters (p < 0.05). Hypothalamic transcriptomic analysis identified 240 differentially expressed genes in the ILA group compared with the CON group, with enrichment of genes involved in neural signaling and appetite regulation. These findings suggest that ILA may influence feeding behavior in weaned piglets, accompanied by numerical increases in feed intake and growth-related parameters, as well as changes in peripheral appetite-related gastrointestinal hormones and hypothalamic transcriptional responses.},
}

@article {pmid43027164,
year = {2026},
author = {Kong, L and Zhu, Y and Liu, B and Wei, H and Li, Y},
title = {Diet-Associated Gut Microbiome Divergence Contributes to Phenotypic Differentiation Among Geographically Structured Populations of Rana dybowskii.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027164},
issn = {2076-2615},
support = {2025 and 2026//Special Project of Rana dybowskii (2025 and 2026) of the De-partment of Agriculture and Rural Affairs of Liaoning Province./ ; },
abstract = {Geographic phenotypic variation is a widespread feature of natural populations, often driven by local environmental heterogeneity and trophic interactions. While the gut microbiome is recognized as a key mediator between environmental resources and host physiology, its role in the adaptive differentiation of amphibians remains insufficiently explored. In this study, we employed an integrative approach-combining morphological measurements, DNA metabarcoding for dietary analysis, and 16S rRNA sequencing for gut microbial profiling-to investigate three geographically structured populations (Dandong [DD], Fushun [FS], and Benxi [BX]) of the Dybowski's frog (Rana dybowskii). The results showed that the morphological characteristics (body weight, head-body length, hindlimb length, etc.) of DD were significantly higher than those of FS and BX. Dietary analysis via gut content DNA metabarcoding identified distinct food structures; notably, the DD population consumed a higher proportion of Dipteran prey (e.g., Smittia). Correspondingly, the gut microbiota showed significant population-level clustering. We identified an enrichment of specific functional bacteria in the DD population, such as Arthrobacter, which is known for its chitin-degrading capabilities, aligning with the consumption of chitin-rich insect prey. Mantel tests further confirmed a strong correlation between dietary composition, microbial community structure, and host morphological traits. These findings suggest that diet-driven gut microbiome variation is consistent with a contributing role in the phenotypic differentiation of R. dybowskii across different habitats, although causal relationships remain to be tested directly. By integrating trophic ecology with microbial landscapes, this study provides new insights into the adaptive evolution and resource management of amphibians in heterogeneous environments.},
}

@article {pmid43027210,
year = {2026},
author = {Muñoz, BX and Benavides, S and Fireman, A and Bortoluzzi, C and Martins Bueno, IJ and Alves Rodrigues, L and Netto, R and Lopes, M and Pais, V and Longhini, G and Lovon, M and Araujo, C and Araujo, L},
title = {Dietary Isoacids Improve Early-Life Feed Efficiency, Reduce Abdominal Fat Deposition, and Modulate Intestinal and Metabolic Responses in Broiler Chickens.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027210},
issn = {2076-2615},
abstract = {This study evaluated the effects of increasing dietary inclusion levels of branched-chain volatile fatty acids, also called isoacids (ISO), on the growth performance, carcass traits, intestinal health, and breast muscle metabolomic profile of broiler chickens. A total of 700 one-day-old male Cobb 500 chicks were assigned to five corn-soybean meal-based diets with 10 replicate pens (14 birds/pen) in a completely randomized design: A Positive Control (PC) diet formulated to meet nutritional requirements was supplemented with 0.0, 0.10, 0.20, 0.40, or 0.60% of ISO (supplied as a blend of isobutyrate and 2-methylbutyrate). Data were analyzed using General Linear Models with orthogonal polynomial contrasts, PERMANOVA for microbiome beta diversity and ANOVA with FDR correction for metabolomics. Growth performance was monitored across feeding phases. At day 42, carcass traits, breast meat quality, intestinal permeability, cecal short-chain fatty acids (SCFAs), and cecal and ileal microbiota were assessed, alongside liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) metabolomics of the Pectoralis major muscle. Dietary ISO significantly improved average daily weight gain (p < 0.0001) and feed conversion ratio (p < 0.0001) during the first 21 days (early-life), with an optimal inclusion level of 0.40%. While overall carcass and breast yields were unaffected, ISO supplementation significantly and quadratically reduced abdominal fat deposition (p < 0.0001), with an optimal inclusion range between 0.10% and 0.40%. ISO did not compromise intestinal permeability or alter microbial alpha diversity, but it significantly restructured the cecal microbiota (beta diversity; Bray-Curtis p = 0.0213) and linearly increased cecal isobutyric acid accumulation in the cecal content (p = 0.0443). Breast muscle metabolomics revealed a dose-dependent, nonlinear response; the 0.40% inclusion level maximized the relative abundance of galactolipids, whereas the highest dose (0.60% ISO) upregulated sphingomyelins, lysophospholipids, and acylcarnitines. In conclusion, a specific dietary ISO supplementation dose of 0.4% serves as an effective nutritional strategy to boost early feed efficiency and reduce abdominal adiposity. Doses exceeding this optimal level, such as 0.60%, offer no further productive benefits and may trigger cellular stress.},
}

@article {pmid43027216,
year = {2026},
author = {Li, N and Li, F and Zhang, M and Zhang, F and Wu, C and Hu, L and Xu, J},
title = {Testicular and Rumen Microbial Responses to Selenium-Enriched Malt in Heat-Exposed Simmental Bulls.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027216},
issn = {2076-2615},
support = {JXSNKYJCRC202442//Jiangxi Academy of Agricultural Sciences/ ; },
abstract = {This study evaluated testicular and rumen microbial responses to selenium-enriched malt in heat-exposed Simmental bulls. Eighteen bulls received a basal diet alone or supplemented to provide target supplemental Se levels of 0.3 or 0.5 mg/kg dietary DM. Metagenomics included six bulls per group, host assays four per group, and RNA sequencing three per group. Compared with controls, the high-dose group had higher serum antioxidant indices and reproductive hormone concentrations, lower inflammatory markers, higher Johnsen scores, and lower TUNEL positivity. Gene-level FDR control identified 23, 1, and 4 differentially expressed genes in the low-dose versus control, high-dose versus control, and high-dose versus low-dose contrasts, respectively. Provider-reported GSEA showed negative normalized enrichment scores for steroid biosynthesis in the control-versus-low-dose and control-versus-high-dose contrasts, indicating enrichment toward the supplemented side under the provider's contrast convention. qPCR showed lower CYP11A1, CYP17A1, SCARB1, and LDLR expression at the low dose, whereas Bax, Bcl-2, and CYP17A1 protein abundance did not differ. Rumen microbial diversity and community composition differed among groups, and two post hoc selected cofactor-related pathways had lower abundance at the low dose. None of the 160 microbiome-testis or 720 microbiome-serum associations survived FDR correction. Supplementation was associated with favorable systemic and testicular histological responses and dose-specific molecular and microbial changes under heat exposure.},
}

@article {pmid43027232,
year = {2026},
author = {Behera, G and Hammer, SE and Holzer, AS and Saleh, M},
title = {Gut Microbiome Assembly and Its Consequences for Disease Susceptibility in Fish.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {21},
pages = {},
pmid = {43027232},
issn = {2076-2615},
support = {10.55776/PIN1743725,//FWF Austrian Science Fund/ ; 101136346//EU Partnership on Animal Health and Welfare (EUP AH&W)/ ; },
abstract = {The assembly of the gut microbiome in fish is a dynamic and tightly regulated process influenced by host genetics, early-life environmental exposure, diet, and aquaculture practices. Increasing evidence indicates that deliberate manipulation of this assembly through probiotics, prebiotics, synbiotics, environmental microbiome management, and husbandry interventions can significantly alter host-microbe interactions and downstream health outcomes. This review synthesizes we have summarized the current understanding about the regulatory principles of gut microbiome assembly in fish and explored the impact of manipulating the microbiome assembly process. Emphasis will be given to the early-life microbial colonization process, which is an important time point for microbiota succession and plays an important role in the development of immunity and resistance against diseases. Aquaculture systems, like recirculating aquaculture system (RAS) and flow-through system, where there is variation in microbiome exposure and water quality, further influence the process of microbiome assembly and pathogen dynamics. Several manipulative techniques, such as live feed enrichment, the seeding of microbes, and the management of water microbiomes, have been successful in inducing the growth of beneficial microbes while suppressing opportunistic pathogens. However, the risk of microbiome dysbiosis, reduction in microbial resilience, and pathogen resistance due to microbiome manipulation cannot be overlooked. Understanding these trade-offs is essential for developing sustainable and effective strategies. By integrating insights from microbiology, immunology, and aquaculture science, this review carries out a systematic PRISMA analysis, highlights the consequences of microbiome manipulation on disease susceptibility, and provides a framework for designing microbiome-informed interventions to enhance fish health and productivity in modern aquaculture systems.},
}

@article {pmid43027332,
year = {2026},
author = {Bhowmic, S and Roy Choudhury, P and Das, P and Banerjee, S and Chakrabarti, J and Juin, SK and Ghosh, S},
title = {Gut Microbiota and Microbial Metabolites in the Regulation of Chemotherapeutic Resistance.},
journal = {Cells},
volume = {15},
number = {21},
pages = {},
pmid = {43027332},
issn = {2073-4409},
support = {NRI-2025-1053//Department of Health Research (DHR), Government of India,/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Drug Resistance, Neoplasm ; Animals ; *Antineoplastic Agents/therapeutic use/pharmacology ; *Neoplasms/drug therapy/microbiology/metabolism ; },
abstract = {Resistance to chemotherapy continues to be a significant challenge for cancer treatment and a contributing factor to treatment failures and tumor progression. Recently, the gut microbiome has emerged as an important modulator of the response to chemotherapy. Numerous pre-clinical and clinical studies have demonstrated a direct association between gut microbiota composition and therapy effectiveness in many cancer types, such as colorectal, breast, pancreatic, gastric, and lung cancers, melanoma, and hematological cancers. Gut microbiota effectively regulate the efficiency of chemotherapeutic agents in various ways, either by biotransformation of chemotherapeutic agents or modulation of host immunity. In addition, microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan metabolites are also involved in the regulation of chemotherapy response through modulating apoptosis, immunity, and epithelial-mesenchymal transition. Finally, dysbiosis induced by chemotherapy and antibiotics has also been reported to reduce the effectiveness of therapy. This review will emphasize the ways in which gut microbiota can modulate chemotherapeutic response and induce chemoresistance. Understanding the interactions between chemotherapeutic drugs and the gut microbiota can help to enhance the efficiency of chemotherapy and find more appropriate personalized treatments.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Drug Resistance, Neoplasm
Animals
*Antineoplastic Agents/therapeutic use/pharmacology
*Neoplasms/drug therapy/microbiology/metabolism

@article {pmid43027372,
year = {2026},
author = {Schwarz, K and Rickert, C and Kendlbacher, FL and Miłek, O and Behm, C and Schäffer, C and Andrukhov, O},
title = {Distinct Polarization of Human Macrophages in Response to Infection with the Periodontitis-Associated Bacteria Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia.},
journal = {Cells},
volume = {15},
number = {21},
pages = {},
pmid = {43027372},
issn = {2073-4409},
support = {P34642//FWF Austrian Science Fund/ ; },
mesh = {Humans ; *Porphyromonas gingivalis/physiology ; *Macrophages/microbiology/immunology/metabolism/pathology ; *Fusobacterium nucleatum/physiology ; *Tannerella forsythia/physiology ; *Periodontitis/microbiology/immunology ; *Cell Polarity ; Cytokines/metabolism ; THP-1 Cells ; },
abstract = {Periodontal health and disease are shaped by a dynamic interaction between the subgingival microbiome and the host immune system, in which gingival macrophages contribute to tissue homeostasis, disease progression, and inflammation resolution. Here, we investigated how three periodontitis-associated bacteria, Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia, shape the polarization of human macrophages in vitro. THP-1 monocytes were differentiated into unpolarized M0 macrophages, or polarized toward the M1 or M2 phenotype, and infected with each bacterium at different multiplicities of infection. Polarization was assessed from the surface expression of CD80 (M1) and CD209 (M2) and from pro- and anti-inflammatory cytokine production, measured by a multiplex assay. The response to P. gingivalis differed strikingly from the two other species. Porphyromonas gingivalis suppressed both M1 and M2 polarization and reduced the levels of several pro- and anti-inflammatory cytokines. In contrast, F. nucleatum and T. forsythia enhanced CD80 expression and pro-inflammatory cytokine production in M1 macrophages and modestly increased pro-inflammatory mediators in M2 macrophages. These findings point to a distinct role for P. gingivalis as a keystone pathogen that subverts the innate immune response, and for F. nucleatum and T. forsythia as periodontal pathobionts.},
}

Humans
*Porphyromonas gingivalis/physiology
*Macrophages/microbiology/immunology/metabolism/pathology
*Fusobacterium nucleatum/physiology
*Tannerella forsythia/physiology
*Periodontitis/microbiology/immunology
*Cell Polarity
Cytokines/metabolism
THP-1 Cells

@article {pmid43027382,
year = {2026},
author = {Ayoub, G},
title = {Is Oxidative Stress a Shared Mechanism Linking Autism Regression, Late Diagnosis, and Sex-Disparate Diagnostic Timing?.},
journal = {Cells},
volume = {15},
number = {21},
pages = {},
pmid = {43027382},
issn = {2073-4409},
mesh = {Humans ; *Oxidative Stress ; *Delayed Diagnosis ; *Autism Spectrum Disorder/diagnosis/metabolism ; *Autistic Disorder/diagnosis ; *Sex Characteristics ; Female ; Male ; Sex Factors ; },
abstract = {Autism spectrum disorder (ASD) research has largely treated early regression, late decline after a period of stability, gradual increases in symptom severity, late diagnosis, and the sex difference in diagnostic timing as separate topics. These phenomena differ in definition, evidence, and plausible mechanism, and diagnostic and recognition processes may explain much of the late-diagnosis and sex-timing findings. This narrative, hypothesis-generating review asks whether a cumulative oxidative and inflammatory burden, arising from environmental chemical exposure, infection and autoimmune activity, and chronic psychosocial stress, and modified by genetic susceptibility, one-carbon metabolism, the gut microbiome, and individual buffering capacity, could contribute to some of these trajectories. We grade the evidence for each link in four tiers (human ASD data, other human data, experimental models, and our hypotheses). Most links rest on associations with ASD risk or on experimental data; no study has linked these exposures to regression or late diagnosis, and oxidative stress may be a consequence or correlate rather than a cause. We therefore define operational terms, derive predictions that could refute the model, and outline the prospective, sex-stratified evidence needed to test it.},
}

Humans
*Oxidative Stress
*Delayed Diagnosis
*Autism Spectrum Disorder/diagnosis/metabolism
*Autistic Disorder/diagnosis
*Sex Characteristics
Female
Male
Sex Factors

@article {pmid43027454,
year = {2026},
author = {Alhodieb, FS},
title = {Emerging Food Fortification and Precision Nutrition: Technologies for Personalized Nutrient Delivery and Health Monitoring.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43027454},
issn = {2304-8158},
abstract = {Food fortification has experienced a revolution because of the process of encapsulation techniques, controlled delivery systems, and personalized nutrition approach. The purpose of this review is to analyze the recent trends in encapsulated and personalized food fortification systems and the possibility of increasing the stability, bioavailability, targeted delivery, and personalized nature of nutrients. A review of the scientific literature was performed, covering topics such as micro- and nanoencapsulation, microfluidization, emulsified systems, omics approaches, nutrigenomics, nutrigenetics, microbiome interventions, 3D/4D food printing technology, wearable biosensors, artificial intelligence dietary analysis, and Internet of Things in foods. According to the reviewed literature, these technological approaches could help protect, distribute, and release vitamins, minerals, probiotics, and bioactive compounds, and help provide the opportunity to develop personalized nutritional approaches. Moreover, integration of omics techniques with advanced food technologies would allow taking into account genetic, metabolic, and microbiome aspects of different nutritional needs. Furthermore, emerging digital and manufacturing technologies would also provide an opportunity to create individualized fortified foods. Nevertheless, there are still issues with regulatory aspects, cost-effectiveness, consumer acceptability, and the equity and privacy of genetic and personal data. In conclusion, the application of controlled-release technology in personalized nutrition techniques holds much promise in creating specialized fortified foods, while additional research is required to establish their safety, effectiveness, affordability, and practical application.},
}

@article {pmid43027480,
year = {2026},
author = {Abou-Emera, OK and Aladhadh, M},
title = {Hen Egg-Derived Bioactive Proteins and Peptides at the Gut Interface: From Molecular Characterization and Digestion to Microbiome Interactions and Prospective Precision Nutrition.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43027480},
issn = {2304-8158},
support = {QU-APC-2026//Qassim University/ ; },
abstract = {Hen eggs (Gallus gallus domesticus) contain bioactive proteins, peptides and lipids, but compound characterization, mechanistic cell and animal studies, and human consumption trials have developed largely in isolation. This narrative review, supported by a documented literature search, follows one pathway: egg composition, molecular characterization, processing and digestion, bioaccessibility, intestinal and microbial interaction, host signaling, and a prospective precision-nutrition outlook. Findings are classified into translational evidence categories (a heuristic classification of experimental systems, not a ranking of study quality) and summarized in a multidimensional evidence matrix. Egg white and yolk proteins, including ovotransferrin, ovomucin and lysozyme, yield characterized peptides, notably the ovotransferrin tripeptides IRW (Ile-Arg-Trp), IQW (Ile-Gln-Trp) and LKP (Leu-Lys-Pro), and ovomucin hydrolysates, whose activities in cell and animal models are compound-specific: LKP, for example, did not reproduce the effect of IRW on insulin resistance in muscle cells. In humans, one small ileostomy study (n = 5) reports higher ileal protein digestibility for cooked than raw egg, short-term trials show that whole-egg intake raises plasma choline, and an antibiotic-suppression study shows that trimethylamine-N-oxide formation after eggs plus phosphatidylcholine depends on gut microbiota. No study identified shows that IRW, IQW or LKP are generated, survive digestion or reach the circulation after ordinary egg consumption, and only six human studies address egg intake and the gut microbiome. Dose-response, delivery-system and safety data are largely missing, and precision nutrition for egg bioactives remains a research framework. Priorities are human pharmacokinetic confirmation, longer trials with shotgun metagenomics and functional readouts, and independent safety testing.},
}

@article {pmid43027607,
year = {2026},
author = {Zhang, H and Xu, K and Chang, Q and Zhen, L and Li, Y and Wang, T and Wang, B and Liu, Y},
title = {Differences in Microbial Community Succession and Caproic Acid Metabolic Dynamics in Upper-Layer Fermenting Grains Between Aged and New Pits During Strong-Flavor Baijiu Fermentation.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43027607},
issn = {2304-8158},
support = {32302031//National Natural Science Foundation of China/ ; },
abstract = {Caproic acid and its ester ethyl caproate are the characteristic flavor compounds of Chinese strong-flavor Baijiu (CSFB), yet their synthesis and esterification in upper-layer fermenting grains (UFG), and how these processes differ between new and aged pits, remain unclear. Compared with aged-pit UFG, the physicochemical parameters, microbial communities, and metabolite dynamics of new-pit UFG likewise followed a largely similar three-stage pattern: early acidification and starch consumption (2-8 d), mid-stage stabilization (10-20 d), and late secondary acid/ester synthesis (30-60 d). The critical divergence lay in butyric/caproic acid synthesis and the eukaryotic community: new-pit UFG produced lower amounts of butyric and caproic acids, and was dominated by taxa of unclear fermentative relevance, lacking the non-Saccharomyces yeasts (Kazachstania, Candida) enriched in aged-pit UFG, whose abundances correlated with ester accumulation. Specifically, new-pit UFG yielded lower concentrations of three of the four major ethyl esters, whereas ethyl lactate was consistently higher than in aged-pit UFG; yet, notably, ethyl butyrate accumulated despite nearly undetectable butyric acid. Correlation analyses identified candidate caproic acid producers (Lactobacillus, Pediococcus, Weissella) and esterification contributors (Candida, Mucor). These findings highlight the importance of the predicted maturity-driven metabolic-ecological network integrity in UFG, suggesting potential for synthetic-microbiome strategies in new-pit fermentation.},
}

@article {pmid43027638,
year = {2026},
author = {Qu, J and Guo, R and Chen, G and Guo, J and Wang, Q},
title = {From Quality Detection to Intelligent Management: A Mechanism-Informed Framework Integrating Foodomics, Microbiome Science and Explainable Artificial Intelligence for Fish Flesh Quality.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43027638},
issn = {2304-8158},
support = {264Z2902G//The Central Government-Guided Local Science and Technology Development Special Project of Hebei Province/ ; 32604918//National Natural Science Foundation of China/ ; },
abstract = {Fish flesh quality is a multidimensional phenotype shaped across the production-post-harvest continuum by interacting metabolic, structural, lipid, redox, and microbial processes. Conventional sensory, physicochemical, biochemical, and instrumental measurements remain essential for defining quality phenotypes, while foodomics and microbiome approaches increasingly resolve the biological mechanisms underlying quality formation and deterioration. This review integrates recent advances in fish flesh quality assessment, foodomics, microbiome science, intelligent sensing, machine learning, and explainable artificial intelligence from a mechanism-informed perspective. Particular emphasis is placed on energy metabolism, lipid remodeling, redox regulation, muscle-fiber and collagen organization, microbial metabolites, and spoilage-related microbial functions that connect biological state with measurable quality traits. We further examine the transition from current-state recognition toward prospective quality prediction, with emphasis on biological interpretability, transferability, external validation, and uncertainty. Building on this evidence, we propose a dual-stage framework in which a context-dependent harvest biological-state vector integrates energetic, structural, lipid/nutritional, redox, and product-associated microbial dimensions to connect pre-harvest quality formation with post-harvest deterioration trajectories. Together, these advances provide a basis for moving from quality detection toward prospective prediction and mechanism-informed intelligent management of fish flesh quality.},
}

@article {pmid43027661,
year = {2026},
author = {Patel, V and Raja, A and Khan, M and Melcher, AA and Chong, I and Young, A},
title = {Precision Radiation Oncology: Molecular Strategies to Enhance Anti-Tumour Responses to Radiotherapy-Beyond Direct Tumour Cell Killing.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027661},
issn = {1422-0067},
mesh = {Humans ; *Neoplasms/radiotherapy/immunology/genetics ; *Precision Medicine/methods ; *Radiation Oncology/methods ; DNA Damage ; Tumor Microenvironment/radiation effects ; Animals ; cGAS-STING Signaling Pathway ; Radiation Tolerance ; },
abstract = {Radiotherapy remains a cornerstone of cancer treatment, yet treatment response continues to be limited by tumour radioresistance and considerable biological heterogeneity. Although advances in radiation delivery have substantially improved dose conformity and reduced toxicity, increasing evidence suggests that optimising therapeutic outcomes will require greater integration of tumour biology into treatment strategies. This review examines emerging molecular approaches that seek to enhance anti-tumour responses to radiotherapy beyond direct tumour cell killing. We discuss the DNA damage response as a therapeutic target for radiosensitisation, highlighting the evolving role of DNA damage response inhibitors in promoting both tumour cytotoxicity and immune activation. We further examine the mechanisms linking radiation-induced DNA damage to anti-tumour immunity, including immunogenic cell death, cGAS-STING signalling, and remodelling of the tumour microenvironment, together with the opportunities and challenges of combining radiotherapy with immune checkpoint inhibition. Finally, we review emerging concepts in precision radiation oncology, including spatially tailored irradiation strategies, genomically informed radiation prescription, radiogenomics, and the influence of the gut microbiome on treatment response. Collectively, these advances support a shift from anatomically guided radiotherapy towards biologically personalised treatment, integrating molecular, immunological and genomic information with normal-tissue susceptibility to improve the therapeutic ratio and enable more precise, patient-centred cancer care.},
}

Humans
*Neoplasms/radiotherapy/immunology/genetics
*Precision Medicine/methods
*Radiation Oncology/methods
DNA Damage
Tumor Microenvironment/radiation effects
Animals
cGAS-STING Signaling Pathway
Radiation Tolerance

@article {pmid43027704,
year = {2026},
author = {Yaish, MW and Mithöfer, A},
title = {Lessons from Plant-Microbe Interactions: Concepts for Improving Plant Nutrition and Stress Tolerance.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027704},
issn = {1422-0067},
support = {IG/SCI/BIOL/24/03//Sultan Qaboos University/ ; },
mesh = {*Stress, Physiological ; Soil Microbiology ; Rhizosphere ; *Plants/microbiology ; Microbiota ; Plant Development ; Crops, Agricultural/microbiology ; },
abstract = {Plant-associated microorganisms, particularly plant growth-promoting bacteria (PGPB), enhance plant nutrition and stress tolerance and offer potential complementary approaches to conventional fertilization and crop protection. However, inconsistent field performance, ecological concerns associated with introducing non-native bacterial strains, and the need for formulations tailored to specific plant genotypes and soil conditions limit their agricultural application. These challenges have stimulated research into complementary strategies for promoting plant growth under favorable and stressful conditions. Here, we review advances and limitations of PGPB-based biofertilizers, focusing on multi-strain consortia, endophytic versus epiphytic microorganisms, and precision agriculture approaches integrating soil microbiome dynamics with plant-genotype-specific formulations. We also examine molecular mechanisms through which PGPB influence plant gene expression, stress signaling, nutrient acquisition, and rhizosphere communication. Building on these insights, we discuss strategies for using beneficial microbial mechanisms to improve abiotic stress tolerance and nutrient uptake. Integrating microbiome-informed biofertilizer development with genetic engineering, crop breeding, and precision agriculture could improve plant resilience. However, successful application requires functional validation and field testing under variable environmental conditions. Such approaches may reduce dependence on external agricultural inputs while improving crop productivity and sustainability. Together, these complementary strategies provide a framework for harnessing plant-microbe interactions to support climate-resilient agriculture and future food security worldwide.},
}

*Stress, Physiological
Soil Microbiology
Rhizosphere
*Plants/microbiology
Microbiota
Plant Development
Crops, Agricultural/microbiology

@article {pmid43027723,
year = {2026},
author = {Zhang, Y and Liu, X and Wang, B and Yin, H and Tian, X and Zhao, J and Xin, S and Wang, H and Ren, Y and Liu, X and Liu, J and Bian, Y and Gu, S and Zhang, H and Wei, T and Gao, L and Lu, X and Shang, H and Xu, J},
title = {IL-10 Beyond Immunosuppression: Unraveling Spatial, Cellular, and Metabolic Mechanisms of Gut Protection.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027723},
issn = {1422-0067},
support = {7242211//Beijing Natural Science Foundation Program/ ; 82474161//National Natural Science Foundation of China/ ; 82174056//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Animals ; *Interleukin-10/metabolism/immunology ; Signal Transduction ; *Gastrointestinal Microbiome/immunology ; Intestinal Barrier Function ; *Immune Tolerance ; Homeostasis ; *Intestinal Mucosa/metabolism/immunology ; Host-Directed Therapy ; },
abstract = {Intestinal homeostasis requires immune tolerance, barrier integrity, tissue repair, and microbiota mutualism. Interleukin-10 (IL-10) is essential, but not merely as an immunosuppressant. Although IL-10 signals via the IL-10R-JAK1/TYK2-STAT3 axis, its outputs are cell-type and context dependent. In macrophages, IL-10 restrains IL-23 production, inflammasome activation, IL-1β release, and metabolic reprogramming. In T cells, it limits pathogenic T helper 17 cell (Th17) responses while stabilizing regulatory cells and promoting metabolically driven IL-10 production. In the epithelium, IL-10 maintains barrier integrity by limiting apoptosis, endoplasmic reticulum (ER) stress, and mucus defects. IL-10 and the gut microbiota engage in reciprocal regulation: microbial metabolites and structural components enhance IL-10 production and receptor responsiveness, whereas IL-10 signaling preserves microbial diversity and ecological resilience. This may help to explain why systemic recombinant IL-10 failed in Crohn's disease (CD)-increasing ligand abundance alone is unlikely to recapitulate endogenous localization or restore refractory target cells. Emerging strategies aim to tune IL-10 signaling through gut-selective delivery, engineered cytokines, conditionally activated prodrugs, regulatory cell approaches, and microbiome or metabolic interventions. Clinical translation requires biomarkers of IL-10R expression, STAT3 responsiveness, macrophage metabolic state, microbial signatures, and acquired IL-10 hyporesponsiveness. Despite the established role of IL-10 in intestinal homeostasis, systemic IL-10 therapy has failed in clinical trials, and there is a lack of effective strategies to restore IL-10 signaling in a spatially and cell-specific manner. The spatially organized, metabolically conditioned homeostatic IL-10 signaling-largely inferred from model systems and awaiting direct spatial validation in human intestine-offers a roadmap for more precise therapy in inflammatory bowel disease and related intestinal disorders.},
}

Humans
Animals
*Interleukin-10/metabolism/immunology
Signal Transduction
*Gastrointestinal Microbiome/immunology
Intestinal Barrier Function
*Immune Tolerance
Homeostasis
*Intestinal Mucosa/metabolism/immunology
Host-Directed Therapy

@article {pmid43027751,
year = {2026},
author = {Park, D and Park, J and Chun, OK and Kwon, EY and Bae, HR},
title = {Integrated Multi-Omics Convergence Scoring Reveals Modular Network Architecture with Age-Associated Mitochondrial Signatures in Sarcopenia.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027751},
issn = {1422-0067},
support = {RS-2024-00342528//National Research Foundation of Korea/ ; RS-2025-25435826//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Sarcopenia/genetics/metabolism/pathology ; Multiomics ; *Aging/genetics/metabolism ; *Gene Regulatory Networks ; *Mitochondria/metabolism/genetics ; Muscle, Skeletal/metabolism ; DNA Methylation ; Transcriptome ; Genome-Wide Association Study ; Gene Expression Profiling ; },
abstract = {Sarcopenia arises from convergent genetic, epigenetic, transcriptomic, metabolic, and microbiome-associated perturbations, yet conventional multi-omics analyses often yield fragmented, layer-specific feature lists. We developed an integrated multi-omics convergence scoring framework that calculates an Integrated Convergence Score (ICS) by combining standardised layer-level statistical evidence, layer-specific pathway context, network features and sarcopenia-specific disease-relevance evidence. We applied it to skeletal muscle transcriptomes from five independent cohorts (208 participants), ageing-associated muscle DNA methylation, and genome-wide association studies of muscle mass and strength, each analysed against its own null distribution. Gene-level changes were few and did not replicate, whereas mitochondrial respiration, mitochondrial translation and contraction pathway scores were lower in sarcopenia in the pooled analysis. These mitochondrial signatures were also lower in ageing-, frailty-, and pre-sarcopenia-related comparisons, indicating a component shared with muscle ageing. The three layers implicated largely distinct mechanisms. Compared with rank-based combined statistics, the ICS top-ranked genes formed a more connected network, which partly reflects the network component of the score. A context map placed the modules within mitochondrial respiration, creatine-based energy buffering, and NAD-PGC-1α signalling. This framework organises fragmented multi-omics evidence into a systems-level gene network associated with sarcopenia and prioritises candidate genes and mechanisms for future functional studies.},
}

Humans
*Sarcopenia/genetics/metabolism/pathology
Multiomics
*Aging/genetics/metabolism
*Gene Regulatory Networks
*Mitochondria/metabolism/genetics
Muscle, Skeletal/metabolism
DNA Methylation
Transcriptome
Genome-Wide Association Study
Gene Expression Profiling

@article {pmid43027762,
year = {2026},
author = {Escobar-Niño, A and Calcis-Marzán, MV and Forján-Miguéns, A and Punta-Sánchez, I and Coste, O and Pérez-Hurtado, A and Fernández-Acero, FJ},
title = {Unlocking the Power of Metaproteomics: A Novel Tool for Enhancing Shorebird Conservation and Blue-Economy Management.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027762},
issn = {1422-0067},
support = {RESBIOMAR LiA 4, SP18//Plan Complementario de I+D+i en el área de Biodiversidad (PCBIO)/ ; FEDER-UCA-2024-A2-14 (2024-095 / PVA / R&D+I FEDER Junta Andalucía / PR)(BIOPAB)//Universidad de Cádiz/ ; },
mesh = {Animals ; *Proteomics/methods ; *Conservation of Natural Resources/methods ; *Birds/metabolism/microbiology ; Feces/microbiology/chemistry ; Metagenomics/methods ; Proteome ; Microbiota ; },
abstract = {Metaproteomics, the large-scale analysis of proteins from environmental or host-associated samples, has emerged as a transformative tool for characterizing microbial communities and their functional roles. Unlike metagenomics or metatranscriptomics, metaproteomics directly captures phenotypic expression, linking molecular function to ecological and physiological outcomes. Beyond its established applications in human microbiome and dietary research, metaproteomics enables the precise identification of food-derived protein biomarkers, including the discrimination of tissue-specific origins. This level of resolution is not attainable through DNA-based approaches. Here, we applied metaproteomics for the first time to analyze the feces of shorebirds in the salt flats and salt marshes of Cadiz Bay, aiming to determine their diet with unprecedented resolution. Conventional methods, based on direct observation or fecal inspection, are labor-intensive and risk losing critical dietary information. By contrast, metaproteomics provides rapid, high-resolution insights, offering a robust alternative for ecological monitoring. Our results demonstrate the potential of this technique to transform natural area management, optimize conservation strategies for avian species, and support the sustainable development of the blue economy. This study highlights metaproteomics as an innovative, cross-sectoral approach capable of advancing both fundamental ecological research and practical conservation outcomes.},
}

Animals
*Proteomics/methods
*Conservation of Natural Resources/methods
*Birds/metabolism/microbiology
Feces/microbiology/chemistry
Metagenomics/methods
Proteome
Microbiota

@article {pmid43027781,
year = {2026},
author = {Alicka, Y and Topi, S and Gaxhja, E and Baldini, G and Orsini, G and Pietropaoli, D and Cifone, MG and Giuliani, M and Altamura, S},
title = {Lip Squamous Cell Carcinoma: A Conceptual Framework for Integrating Molecular, Immune and Microenvironmental Drivers.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027781},
issn = {1422-0067},
support = {Funding: This study was founded by University of L'Aquila, Grant "VITALITY06¬_CIFONE".//University of L'Aquila/ ; },
mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Carcinoma, Squamous Cell/pathology/genetics/etiology/immunology ; Biomarkers, Tumor/genetics ; MicroRNAs/genetics ; Epigenesis, Genetic ; Ultraviolet Rays/adverse effects ; Cutaneous Squamous Cell Carcinoma ; Animals ; },
abstract = {Lip squamous cell carcinoma (LSCC) is a distinct subtype of head and neck squamous cell carcinoma strongly associated with ultraviolet (UV) radiation exposure and characterized by unique molecular, immune, and microenvironmental features. Although UV-induced photodamage represents the principal initiating event, increasing evidence indicates that LSCC progression results from complex interactions among genetic and epigenetic alterations, dysregulated signaling pathways, chronic inflammation, immune dysregulation, host-microbiome dynamics, and tumor microenvironment (TME) remodeling. Recent advances have expanded the traditional view of LSCC by highlighting the contributions of UV-induced DNA damage, tumor protein p53 (TP53) alterations, epigenetic reprogramming, aberrant activation of key signaling pathways, and progressive immune escape mechanisms. In parallel, growing attention has focused on the role of cancer-associated fibroblasts (CAFs), stromal remodeling, microbial dysbiosis, and disruption of the microbiome-immune-metabolic axis as important modulators of disease progression and biological heterogeneity. Emerging biomarkers, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), epigenetic signatures, liquid-biopsy analytes, immune-related markers, and microbiome-associated profiles, together with artificial intelligence (AI)-based analytical approaches, are creating new opportunities for diagnosis, risk stratification, disease monitoring, and precision oncology. Rather than providing a conventional descriptive overview, this review proposes an integrated conceptual framework in which molecular, immune, microbial, and microenvironmental drivers interact through continuous bidirectional crosstalk to shape LSCC initiation, progression, therapeutic responsiveness, and clinical heterogeneity. This system-oriented perspective may provide a foundation for future biomarker-guided and biologically informed approaches to LSCC management.},
}

Humans
*Tumor Microenvironment/immunology/genetics
*Carcinoma, Squamous Cell/pathology/genetics/etiology/immunology
Biomarkers, Tumor/genetics
MicroRNAs/genetics
Epigenesis, Genetic
Ultraviolet Rays/adverse effects
Cutaneous Squamous Cell Carcinoma
Animals

@article {pmid43027795,
year = {2026},
author = {Issilbayeva, A and Kozhakhmetov, S and Kushugulova, A and Askarova, S and Kaiyrlykyzy, A and Tuigunov, D and Dolmatova, O and Zholdassova, Z and Omarov, Y and Nurgozhin, T},
title = {Gut Microbiome Alterations in Alzheimer's Disease: A Shotgun Metagenomic Case-Control Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027795},
issn = {1422-0067},
support = {AP23489983//Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; },
mesh = {Humans ; *Alzheimer Disease/microbiology ; Case-Control Studies ; Female ; *Gastrointestinal Microbiome/genetics ; *Metagenomics/methods ; Male ; Aged ; Metagenome ; Shotgun Sequencing ; Cross-Sectional Studies ; Bacteria/classification/genetics ; Kazakhstan ; },
abstract = {The gut microbiome has been proposed as a contributor to Alzheimer's disease (AD) pathogenesis via the microbiota-gut-brain axis, but findings across cohorts are inconsistent and scarce data exist from Central Asian populations. We used shotgun metagenomic sequencing to compare the gut microbiome of AD patients and cognitively healthy controls from Kazakhstan. In a cross-sectional case-control study (35 AD, 39 Control), we profiled taxonomic and functional (HUMAnN pathway) composition, and compared alpha/beta diversity, individual taxa and pathways, and their association with clinical and demographic variables (Mann-Whitney U test, PERMANOVA/PERMDISP, OLS regression, all BH-FDR corrected, sensitivity analysis using ANCOM-BC2), with sensitivity analyses adjusting for age and BMI and applying Bonferroni correction. Within the AD group, circulating adiponectin-measured only in this group-was examined for associations with microbiome features in an exploratory analysis. Alpha diversity was lower in AD (q < 0.05). Community composition also separated by group on PERMANOVA (R[2] = 8.6%, p = 0.001), and this separation held after adjusting for age and BMI. A total of 178 taxa differed significantly between groups (BH-FDR; 37 were also Bonferroni-significant), most prominently depletion of Faecalibacterium and enrichment of Eisenbergiella and Desulfovibrio in AD; 100 pathways differed significantly (20 Bonferroni-significant). Three clinical/demographic variables (total bilirubin, atherogenic index, BMI) were associated with specific taxa or pathways. Within the AD group, adiponectin correlated negatively with the pathway assimilatory sulfate reduction IV (rho = -0.60, q = 0.015). AD in this Central Asian cohort was associated with a less diverse, compositionally distinct gut microbiome, with depletion of butyrate-producing Firmicutes and enrichment of sulfate-reducing taxa, alongside other taxa whose direction of association differed from prior reports.},
}

Humans
*Alzheimer Disease/microbiology
Case-Control Studies
Female
*Gastrointestinal Microbiome/genetics
*Metagenomics/methods
Male
Aged
Metagenome
Shotgun Sequencing
Cross-Sectional Studies
Bacteria/classification/genetics
Kazakhstan

@article {pmid43027832,
year = {2026},
author = {Scheithauer, TPM and Olgiati, E and Verheij, E and van Butselaar, W and Ossendrijver, M and van der Wurff, M and Schuren, FHJ},
title = {Gut Microbiota-Mediated SN-38G Metabolism In Vitro: Effects of Murraya koenigii and Ruta graveolens.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027832},
issn = {1422-0067},
mesh = {Humans ; *Irinotecan/metabolism ; *Ruta/chemistry ; *Plant Extracts/pharmacology/chemistry ; *Murraya/chemistry ; *Gastrointestinal Microbiome/drug effects ; Glucuronidase/genetics/metabolism ; *Camptothecin/analogs & derivatives/metabolism ; Feces/microbiology ; },
abstract = {The influence of the human microbiome on health and disease has been extensively studied over the past two decades. More recently, the microbiota has also been implicated in modulating the efficacy and toxicity of various drugs, including cancer therapies. This study focuses on irinotecan, a chemotherapeutic prodrug used in colorectal cancer treatment. Irinotecan is converted to the active metabolite SN-38, which is then glucuronidated in the liver to form the inactive metabolite SN-38G. Following biliary secretion into the intestine, microbial enzymes can cleave the glucuronide group and release SN-38, a process that may contribute to gastrointestinal toxicity. Human fecal microbiota converted SN-38G to SN-38 in vitro. Antibiotic treatment markedly reduced conversion, indicating that microbial activity accounted for most of the conversion under these conditions. In an exploratory screen, extracts from Murraya koenigii and Ruta graveolens reduced SN-38G conversion. Differences in community composition and beta-glucuronidase gene abundance were observed after extract exposure. These results show microbiota-dependent SN-38G conversion in vitro and identify compounds and plant extracts that delay or inhibit this conversion. Whether this effect is caused by direct inhibition of microbial beta-glucuronidase or by more generic microbiota effects is open for future research.},
}

Humans
*Irinotecan/metabolism
*Ruta/chemistry
*Plant Extracts/pharmacology/chemistry
*Murraya/chemistry
*Gastrointestinal Microbiome/drug effects
Glucuronidase/genetics/metabolism
*Camptothecin/analogs & derivatives/metabolism
Feces/microbiology

@article {pmid43027911,
year = {2026},
author = {Wang, Y and Sun, ZJ and Qi, HL and Zhao, D and Xing, XD and Jiang, JD and Gao, TL},
title = {The Impact of Intratumoral Bacterial Response to Vaccine Therapy in Cancer Treatment.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027911},
issn = {1422-0067},
support = {JYB2025XDXM609//Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China/ ; 2026-XS-22//Academic Symposium Project on Engineering Science and Technology of the Chinese Academy of Engineering/ ; 82374061//National Natural Science Foundation of China/ ; 2026ZD01910104//National Science and Technology Major Project/ ; 2026‑XZ‑098//Science and Technology Strategic Consulting Project of the Chinese Academy of Engineering/ ; 2026-I2M-SXZX11-03//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; },
mesh = {Animals ; Female ; Mice ; *Microbiota/immunology ; *Cancer Vaccines/immunology ; *Papillomavirus Vaccines/immunology ; Mice, Inbred C57BL ; Vaccines, DNA/immunology ; Oncogene Proteins, Viral/immunology/genetics ; Papillomavirus E7 Proteins/immunology/genetics ; *Neoplasms/therapy/immunology/microbiology ; Immunotherapy ; Humans ; Repressor Proteins ; },
abstract = {Therapeutic Human papillomavirus (HPVs) vaccines are designed to enhance the immunogenicity of HPV and promote the elimination of tumor cells effectively. Mounting evidence implies that tumor-resident microbiomes may influence therapeutic outcomes through immune modulation. In this study, we evaluated whether the intratumoral microbiota affects the efficacy of the therapeutic HPV vaccine. We analyzed RNA sequencing data from tumor tissues of C57BL/6N female mice treated with a DNA vaccine incorporating HPV16 E6/E7 antigens fused with the chemokine CCL11. Microbial community data were acquired using the PathSeq bioinformatics pipeline. Alpha diversity was estimated using the Shannon index and the number of observed taxonomic features, while beta diversity was assessed via principal coordinate analysis (PCoA) based on Bray-Curtis distance. Linear discriminant analysis Effect Size (LEfSe) analysis was performed to identify differentially abundant microbial taxa. Immune cell infiltration was characterized using the xCell deconvolution method. The analysis revealed significant divergence in both the alpha- and beta-diversity metrics of intratumoral microbiota, associated with treatment responsiveness. Vaccinated groups exhibited enriched abundances of the phyla Proteobacteria, together with a concomitant reduction in Firmicutes and Actinobacteria, and were associated with a positive response to cancer immunotherapy. Additionally, intratumoral microbiome composition and diversity correlated with the increased infiltration of CD8[+] T cells, natural killer T (NKT) cells, and myeloid cells. This study identifies intratumoral microbiota remodeling as a key feature of therapeutic HPV vaccine response. The observed coordination between bacterial signatures and immune cell infiltration is associative and raises the hypothesis that intratumoral bacteria may modulate, rather than drive, antitumor immunity. These findings support the development of intratumoral microbiota profiling and highlight the potential for microbiota-targeted strategies to enhance cancer immunotherapy efficacy.},
}

Animals
Female
Mice
*Microbiota/immunology
*Cancer Vaccines/immunology
*Papillomavirus Vaccines/immunology
Mice, Inbred C57BL
Vaccines, DNA/immunology
Oncogene Proteins, Viral/immunology/genetics
Papillomavirus E7 Proteins/immunology/genetics
*Neoplasms/therapy/immunology/microbiology
Immunotherapy
Humans
Repressor Proteins

@article {pmid43027921,
year = {2026},
author = {Cebatoriene, D and Bruzaite, A and Vilkeviciute-Petraite, A and Zaliuniene, D and Lukosevicius, R and Skieceviciene, J and Kupcinskas, J and Liutkeviciene, R},
title = {Nasopharyngeal Microbial Signatures Associated with Anti-VEGF Therapeutic Outcomes in Exudative Age-Related Macular Degeneration: A Pilot Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027921},
issn = {1422-0067},
support = {S-MIP-23-96//Research Council of Lithuania/ ; },
mesh = {Humans ; Pilot Projects ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Microbiota ; *Macular Degeneration/drug therapy/microbiology ; *Nasopharynx/microbiology ; Female ; Male ; Aged ; RNA, Ribosomal, 16S/genetics ; Aged, 80 and over ; Treatment Outcome ; *Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Exudative age-related macular degeneration (AMD) is driven by choroidal angiogenesis, and the response to anti-vascular endothelial growth factor (anti-VEGF) therapy varies between patients. In this pilot study, we investigated whether the pretreatment nasopharyngeal microbiota differs between patients with exudative AMD and controls and whether it is associated with treatment response. Nasopharyngeal swabs were analysed by 16S rRNA gene (V3-V4) amplicon sequencing; after removal of host-derived, chloroplast and contaminant sequences and rarefaction, 55 samples (25 patients and 30 controls) were retained. Treatment response was assessed six months after starting therapy. Community composition was compared using permutational multivariate analysis of variance (PERMANOVA) adjusted for age, sex and statin use. Alpha and beta diversity did not differ between patients and controls (Shannon index, p = 0.892; PERMANOVA, p = 0.067). Pretreatment community composition differed between 19 responders and five non-responders (Bray-Curtis R[2] = 0.057, p = 0.015; weighted UniFrac R[2] = 0.143, p = 0.006), and non-responders had lower diversity (observed ASVs, p = 0.004). Non-responders had a higher relative abundance of Corynebacterium (median 71% vs. 19%; p = 0.009), which did not remain significant after correction for all genera tested. Pretreatment nasopharyngeal microbiota composition was associated with the response to anti-VEGF therapy but not with AMD status. These preliminary findings require confirmation in larger, independent cohorts.},
}

Humans
Pilot Projects
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Microbiota
*Macular Degeneration/drug therapy/microbiology
*Nasopharynx/microbiology
Female
Male
Aged
RNA, Ribosomal, 16S/genetics
Aged, 80 and over
Treatment Outcome
*Angiogenesis Inhibitors/therapeutic use

@article {pmid43027932,
year = {2026},
author = {Kutrasaeng, N and Kawicha, P and Sangdee, A and Nakbanpote, W},
title = {Ecological Responses of Cyanotis arachnoidea C.B. Clarke and Its Rhizosphere Microbiome in Zinc Mine Tailings: Insights for Post-Mining Restoration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027932},
issn = {1422-0067},
support = {//Mahasarakham University/ ; },
mesh = {*Rhizosphere ; *Zinc/metabolism/toxicity ; *Mining ; Biodegradation, Environmental ; *Microbiota ; Soil Microbiology ; Cadmium/metabolism ; Soil Pollutants/metabolism/toxicity ; Bacteria/classification/genetics ; Chlorophyll/metabolism ; },
abstract = {Mining activities severely disrupt soil ecosystems through heavy metal contamination. This study evaluated the phytoremediation potential and rhizosphere microbial dynamics of Cyanotis arachnoidea C.B. Clarke (confirmed via rbcLa and trnH-psbA barcoding), a native plant from Thai zinc mines. Pot experiments demonstrated that plants grown in tailings-contaminated soil exhibited reduced growth and distinct leaf reddening, accompanied by significantly elevated anthocyanin levels. Conversely, proline levels decreased, whereas chlorophyll content and antioxidant parameters (total phenolic content (TPC), total flavonoid content (TFC), and free radical scavenging activity (FRSA)) changed only slightly. Based on zinc (Zn) and cadmium (Cd) uptake and translocation profiles, growth characteristics, and physiology, C. arachnoidea was classified as a highly Zn-tolerant phytostabilizer and a high-translocating Cd excluder. Furthermore, high-throughput sequencing (HTS) and culture-dependent analyses demonstrated that metal toxicity reduced bacterial alpha diversity but selectively enriched stress-tolerant taxa-such as Sphingomonas, Bacillus, Bacteroidota, and Chloroflexi-compared with the nutrient-cycling Acidobacteriota that dominated the cover soil. Collectively, its physiological adaptability, capacity for Zn phytostabilization, effective Cd exclusion strategy, and association with a stress-resilient microbiome make C. arachnoidea a promising candidate for the ecological restoration of multi-metal-contaminated sites.},
}

*Rhizosphere
*Zinc/metabolism/toxicity
*Mining
Biodegradation, Environmental
*Microbiota
Soil Microbiology
Cadmium/metabolism
Soil Pollutants/metabolism/toxicity
Bacteria/classification/genetics
Chlorophyll/metabolism

@article {pmid43027950,
year = {2026},
author = {Antonetti, L and Longo, S and Cardellini, M and Casagrande, V and Menghini, R and Cicalini, I and Pieragostino, D and Poggiogalle, E and Frigerio, F and Piciocchi, C and De Laurenzi, V and Savastano, S and Donini, LM and Mingrone, G and Federici, M},
title = {Use of 16S rRNA Gut Microbiome Analysis to Identify Shared Microbial Signatures Across Metabolic Syndrome Components in Obese Subjects.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027950},
issn = {1422-0067},
support = {PRIN 2017FM74HK//Ministero dell'università e della ricerca/ ; DARE PNC0000002//Ministero dell'università e della ricerca/ ; },
mesh = {Humans ; *Metabolic Syndrome/microbiology ; *Obesity/microbiology/complications ; *RNA, Ribosomal, 16S/genetics ; *Gastrointestinal Microbiome/genetics ; Female ; Male ; Middle Aged ; *Bacteria/genetics/classification ; Cross-Sectional Studies ; Adult ; },
abstract = {Gut microbiota (GM) alterations and related metabolic outputs have been implicated in metabolic syndrome (MetS) and early cardiometabolic risk. However, the associations between GM alterations and MetS, and their relationship with the marked interindividual variability in cardiovascular risk, remain incompletely defined. We conducted a cross-sectional study in individuals with obesity (n = 176) to evaluate associations between GM features and MetS clinical traits using 16S amplicon profiling data. Prevalence of individual MetS traits was 37.4% for hyperglycemia, 23.4% for hypertriglyceridemia, 54.0% for hypertension, and 52.1% for low HDL cholesterol, with 51.1% of participants meeting criteria for MetS overall. Comparative analysis of 16S rRNA amplicon sequencing data identified a shared gut microbial signature comprising 45 ASVs across MetS clinical components. Members of Prevotellaceae and Ruminococcaceae were consistently reduced in MetS, whereas Veillonella and Streptococcus were enriched. Reduced microbial alpha diversity was observed in individuals with MetS. PICRUSt2-based functional inference indicated lower representation of pathways related to complex carbohydrate utilization and short-chain fatty acid (SCFA) metabolism in MetS-positive individuals. Our results, derived from two independent datasets, indicate that MetS is associated with a depletion of bacterial taxa involved in complex carbohydrate metabolism and SCFA production.},
}

Humans
*Metabolic Syndrome/microbiology
*Obesity/microbiology/complications
*RNA, Ribosomal, 16S/genetics
*Gastrointestinal Microbiome/genetics
Female
Male
Middle Aged
*Bacteria/genetics/classification
Cross-Sectional Studies
Adult

@article {pmid43027956,
year = {2026},
author = {Rehman, SU and Tharwat, M and Shaukat, A and Alkheraif, AA and Ali, R},
title = {Integrated Host Genome Rumen Microbiome Metabolome Prediction of Low-Methane, High-Feed-Efficiency Sheep Under Climate Stress.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027956},
issn = {1422-0067},
support = {QU-APC-2026//Qassim University/ ; },
mesh = {Animals ; *Methane/metabolism ; *Rumen/microbiology/metabolism ; *Metabolome ; Sheep/microbiology/genetics/metabolism ; Multiomics ; *Gastrointestinal Microbiome ; Climate ; Genomics ; Animal Feed ; *Stress, Physiological ; *Microbiota ; Metabolomics ; },
abstract = {Sheep are well adapted to marginal grazing systems and provide important products such as wool, milk and meat. However, microbial fermentation in the rumen and reticulum generates enteric methane, which contributes to greenhouse gas emissions from livestock production. Both methane emissions and feed efficiency show heritable variation, while host genetics can also shape rumen microbial composition through complex host-microbe interactions. This review explores how host genomics, rumen microbiome profiles, methanogenic archaeal communities, and rumen and blood metabolomics can be combined to identify biomarkers of low methane emissions and improved feed efficiency, particularly under environmental stress. Evidence suggests that methane production is repeatable and genetically influenced, and that rumen microbiome composition is associated with methane emission and feed efficiency, although current evidence does not show that specific microbial taxa directly cause these traits. Integrating host genotype with microbial and metabolic information may therefore improve statistical prediction of methane emissions and residual feed intake, which is not the same as identifying validated biomarkers or showing biological causation. Nevertheless, reliable microbial biomarkers have yet to be established, and validation across breeds, diets, and production environments remains limited. Heat stress adds further complexity by altering rumen fermentation, oxidative status, and microbial community structure, yet integrated omics research under climatic stress remains scarce. Future studies should prioritize longitudinal, multi-breed designs, standardized methane phenotyping, and coordinated multi-omics analyses to develop robust biomarkers for sustainable, low-emission sheep production.},
}

Animals
*Methane/metabolism
*Rumen/microbiology/metabolism
*Metabolome
Sheep/microbiology/genetics/metabolism
Multiomics
*Gastrointestinal Microbiome
Climate
Genomics
Animal Feed
*Stress, Physiological
*Microbiota
Metabolomics

@article {pmid43027969,
year = {2026},
author = {Akhtar, N and Ahlawat, Y and Singh, A and Wani, AK and Panda, SP and Kumar, A and Patel, LJ and Stevanato, P and Celletti, S},
title = {Microbial Siderophores for Sustainable Agriculture: Stress Tolerance, Biocontrol, Mechanism, and Omics Integration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027969},
issn = {1422-0067},
mesh = {*Siderophores/metabolism ; *Stress, Physiological ; Multiomics ; *Agriculture/methods ; Soil Microbiology ; Iron/metabolism ; },
abstract = {Microbial siderophores play an important role in improving plant tolerance to abiotic and biotic stresses. Beyond iron acquisition, they support plant health by regulating oxidative stress, chelating toxic metals, and mediating beneficial plant-microbe interactions. This review highlights the role of siderophore-producing microbes in mitigating salinity, drought, alkaline stress, and metal toxicity, as well as in the improvement of nutrient solubilization and uptake. It also delineates environmental and physiological factors affecting siderophore production. The review additionally explores how the microbial interactions within soil consortia moderate siderophore biosynthesis and bio-control activity. Advances in multi-omics and genome editing approaches are discussed for identifying important genes and pathways associated with siderophore-mediated stress tolerance. The mechanisms behind siderophore-mediated stress tolerance are discussed, mainly their involvement in pathogen suppression through iron competition and activation of induced systemic resistance. Furthermore, it addresses the commercialization challenges and integration of siderophore applications into precision agriculture, aligning their agricultural and environmental benefits with the United Nations Sustainable Development Goals.},
}

*Siderophores/metabolism
*Stress, Physiological
Multiomics
*Agriculture/methods
Soil Microbiology
Iron/metabolism

@article {pmid43027970,
year = {2026},
author = {Yao, Y and Zhang, X and Li, L and Fei, C and Zhang, Y and Huang, S and Zong, Y and Zhu, L and Cao, Y and Li, T and Shao, M and Zheng, Y},
title = {The Seminal Microenvironment as a Potentially Tractable Interface Between Metabolic Disease and Sperm Damage.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43027970},
issn = {1422-0067},
support = {82174389//National Natural Science Foundation of China/ ; 82474330//National Natural Science Foundation of China/ ; zyyzdxk-2023251//High-level Key Discipline of the National Administration of Traditional Chinese Medicine-Traditional Chinese constitutional medicine/ ; JYB2025XDXM612//Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China/ ; },
mesh = {Humans ; Male ; Animals ; *Spermatozoa/metabolism/pathology ; *Metabolic Diseases/metabolism/pathology ; *Semen/metabolism/microbiology ; Oxidative Stress ; *Cellular Microenvironment ; *Infertility, Male/metabolism/pathology ; },
abstract = {Male reproductive disorders are increasingly linked to metabolic diseases, but mechanistic research remains predominantly focused on the testis. The seminal microenvironment, shaped by epididymal and accessory-gland secretions, contains metabolites, lipids, ions, cytokines, extracellular vesicles, and microbial products, and may act as a metabolically responsive post-testicular interface that continues to influence sperm after spermatogenesis. Obesity, insulin resistance, dyslipidemia, and chronic inflammation can remodel this environment by disrupting secretory activity, redox homeostasis, immune signaling, and microbial ecology. These changes may converge on oxidative and inflammatory pathways, promoting membrane lipid peroxidation, mitochondrial dysfunction, impaired motility and capacitation, oxidative DNA base lesions, DNA fragmentation, and potentially epigenetic alterations. Mouse studies separately report obesity-associated epididymal vesicle remodeling and RNA-dependent changes in embryonic gene expression. In this Review, we examine the regulation and metabolic remodeling of the seminal microenvironment, how these changes may translate systemic metabolic stress into sperm injury, and emerging interventions including metabolic correction, antioxidant strategies, and microbiome-targeted approaches. Overall, current evidence remains largely observational and cross-sectional, with additional technical limitations in low-biomass seminal microbiome studies. Longitudinal and mechanistic studies are therefore needed to determine whether the seminal microenvironment is a causal mediator of metabolic infertility and a clinically tractable target for mechanism-guided preconception care.},
}

Humans
Male
Animals
*Spermatozoa/metabolism/pathology
*Metabolic Diseases/metabolism/pathology
*Semen/metabolism/microbiology
Oxidative Stress
*Cellular Microenvironment
*Infertility, Male/metabolism/pathology

@article {pmid43028038,
year = {2026},
author = {Unlu, O and Demirci, M},
title = {Oral Microbiome-Host Epigenetic Interactions in Oral Carcinogenesis: A Molecular Perspective.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028038},
issn = {1422-0067},
mesh = {Humans ; *Mouth Neoplasms/microbiology/genetics/pathology ; *Microbiota ; *Epigenesis, Genetic ; Tumor Microenvironment ; *Carcinogenesis/genetics ; DNA Methylation ; *Carcinoma, Squamous Cell/microbiology/genetics ; Animals ; },
abstract = {Oral squamous cell carcinoma is still found late, and the tumor microenvironment is complicated enough that treatment often fails even when the diagnosis is timely. While genetic mutations partially account for this pathogenesis, they do not fully explain tumor behavior. Attention has therefore shifted to the microbial community around the tumor, which appears to contribute to malignancy less through the genome than through the host epigenome. This review is about the mechanism rather than about cataloging which species are present. We follow what Porphyromonas gingivalis, Fusobacterium nucleatum and Candida albicans do to DNA methylation, histone modification and non-coding RNA expression in host cells. While chronic inflammation plays a well-established role, bacterial and fungal metabolites also reach chromatin directly, and the resulting changes silence tumor suppressors and release oncogenic signaling in epithelium and stroma alike. We then ask what this means for tumor heterogeneity, for immune escape, and for progression, and we close with the two clinical questions that follow: whether salivary microbial and methylation signatures are usable for early detection, and whether epigenetic drugs can be aimed at the microbial component of the oral tumor microenvironment. In conclusion, the oral microbiome-epigenome axis acts as a crucial driver of tumor progression and microenvironmental immunosuppression. While translating these mechanistic insights into clinical practice necessitates rigorous in vivo validation, integrating microbiota-directed interventions with epigenetic therapies represents a highly promising frontier for the early detection and comprehensive management of OSCC.},
}

Humans
*Mouth Neoplasms/microbiology/genetics/pathology
*Microbiota
*Epigenesis, Genetic
Tumor Microenvironment
*Carcinogenesis/genetics
DNA Methylation
*Carcinoma, Squamous Cell/microbiology/genetics
Animals

@article {pmid43028045,
year = {2026},
author = {Sadurski, J and Staniszewski, A and Muyanlı, EB and Yılmaz, R and Waśko, A},
title = {Global Analysis of Public Cheese Microbiomes Reveals Widespread Bacterial Taxa and Geographic Community Structure.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028045},
issn = {1422-0067},
support = {SD/81/TŻ/2023//Doctoral School of the University of Life Sciences in Lublin/ ; },
mesh = {*Cheese/microbiology ; *Microbiota/genetics ; *Bacteria/classification/genetics ; Metagenomics/methods ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Geography ; Biodiversity ; },
abstract = {Cheese microbiomes remain difficult to compare globally because public sequencing datasets are fragmented and methodologically heterogeneous. Here, we curated 14,203 sequencing records from 233 BioProjects and retained 8910 records from 112 BioProjects for standardized reanalysis, establishing a global comparative framework for cheese microbiome research. Three taxonomic profiling pipelines (QIIME2, Kraken2 and mOTUs) recovered broadly consistent genus-level patterns dominated by lactic acid bacteria, although quantitative concordance varied between methods and study collections. Whole-genome shotgun analysis identified 12 widespread bacterial species independently detected in at least 50% of BioProjects by both Kraken2 and mOTUs, with Lactococcus lactis, Streptococcus thermophilus and Lactococcus cremoris detected in at least 84% of BioProjects in both analyses. Geographic structure remained evident after accounting for dominant community composition: sample-origin country explained 36.6% of community variation in the primary analysis and remained associated with community composition in balanced subsampling and analyses removing or continuously adjusting for five dominant lactic acid bacterial genera. However, public datasets were strongly geographically imbalanced, with European BioProjects dominating the available collection. Together, these results establish a reproducible framework and comparative baseline for investigating cheese microbiome diversity, geographic structure and cross-study patterns across globally distributed public sequencing datasets.},
}

*Cheese/microbiology
*Microbiota/genetics
*Bacteria/classification/genetics
Metagenomics/methods
Phylogeny
RNA, Ribosomal, 16S/genetics
Geography
Biodiversity

@article {pmid43028091,
year = {2026},
author = {Margul, K and Krawczyk, A},
title = {Gut Microbiota as a Potential Modulator of Response to Biologic and Small-Molecule Therapies in Inflammatory Bowel Disease.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028091},
issn = {1422-0067},
support = {2025/57/B/NZ4/00352//National Science Centre/ ; },
mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/drug therapy/therapy/immunology ; *Gastrointestinal Microbiome/drug effects ; Animals ; Intestinal Barrier Function ; },
abstract = {The therapeutic landscape of inflammatory bowel disease (IBD) has expanded substantially with the development of biologic and small-molecule therapies. Nevertheless, many patients fail to respond to these treatments or experience a secondary loss of response. The mechanisms underlying treatment failure remain incompletely understood. Given the ability of gut microorganisms to modify therapeutic compounds, sustain pro-inflammatory immune activation, alter intestinal barrier function and produce bioactive metabolites, the gut microbiota may represent an important modulator of therapeutic response. To summarize current evidence on the role of the gut microbiota in response to biologic and small-molecule therapies in IBD, with particular emphasis on potential mechanisms of drug-microbiota interactions and their implications for treatment response and non-response. Accumulating evidence suggests that the gut microbiota may influence therapeutic efficacy through direct modification of drugs and indirect effects mediated by host immunity, intestinal barrier function and microbial metabolites. Microbial signatures associated with response to individual biologic therapies have been identified, although findings remain heterogeneous. Emerging evidence also indicates that non-bacterial components of the gut ecosystem may contribute to treatment response. The gut microbiota represents a biologically plausible modulator of therapeutic response in IBD. Integration of microbiome data with host genetic and immunological features may help identify biomarkers capable of predicting response to individual therapeutic agents.},
}

Humans
*Inflammatory Bowel Diseases/microbiology/drug therapy/therapy/immunology
*Gastrointestinal Microbiome/drug effects
Animals
Intestinal Barrier Function

@article {pmid43028152,
year = {2026},
author = {Lasagna, A and Andreoni, M and Silvestris, N and Pedrazzoli, P},
title = {Antimicrobial Resistance and Infectious Complications in Cancer Immunotherapy: CAR-T Cells, Bispecific Antibodies and Immune Checkpoint Inhibitors.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028152},
issn = {1422-0067},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/adverse effects ; *Neoplasms/therapy/immunology/complications ; *Antibodies, Bispecific/therapeutic use/adverse effects ; *Immunotherapy, Adoptive/adverse effects/methods ; *Immunotherapy/adverse effects/methods ; *Drug Resistance, Microbial ; },
abstract = {Cancer immunotherapies, including chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies (BsAbs), and immune checkpoint inhibitors (ICIs), have improved outcomes across hematologic and solid malignancies. Infection risk remains heterogeneous and depends on treatment platform, target antigen, lymphodepletion, immune reconstitution, concomitant immunosuppression, and supportive care. This narrative review synthesizes clinical trials, observational studies, and guidance identified through PubMed/MEDLINE, reference screening, and a targeted literature update through October 2026. It focuses on infection incidence, microbiological spectrum, antimicrobial resistance (AMR), multidrug-resistant (MDR) colonization and infection, antimicrobial exposure, prevention, and stewardship. Severe infections can be frequent with BCMA-directed BsAbs: the MagnetisMM-3 study reported grade 3-4 infections in 39.8% of elranatamab-treated patients, while a pooled global teclistamab cohort reported grade 3-4 infections in 55.3%; these estimates are study-specific and are influenced in part by COVID-19. Direct AMR evidence is concentrated in CAR-T and broader cellular-therapy cohorts, while comparable data for BsAbs and ICIs remain limited. Associations between broad-spectrum antibiotic exposure, microbiome disruption, and CAR-T outcomes are clinically important but remain vulnerable to confounding. Prevention should integrate immune status, prior microbiology, antimicrobial exposure, and local resistance patterns rather than infer resistance risk from treatment platform alone. Prospective studies using harmonized outcomes are needed to improve individualized infection prevention and antimicrobial stewardship.},
}

Humans
*Immune Checkpoint Inhibitors/therapeutic use/adverse effects
*Neoplasms/therapy/immunology/complications
*Antibodies, Bispecific/therapeutic use/adverse effects
*Immunotherapy, Adoptive/adverse effects/methods
*Immunotherapy/adverse effects/methods
*Drug Resistance, Microbial

@article {pmid43028246,
year = {2026},
author = {Pető, A and Sipos, D and Kappéter, Á and Feiszt, Z and Dembrovszky, F and Halda-Kiss, B and Péterfi, Z},
title = {Fecal Microbiota Transplantation in the Treatment Strategy of Inflammatory Bowel Disease: Molecular Mechanisms, Clinical Evidence, and the Transition Toward Defined Microbial Therapeutics.},
journal = {International journal of molecular sciences},
volume = {27},
number = {21},
pages = {},
pmid = {43028246},
issn = {1422-0067},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/therapy ; },
abstract = {Inflammatory Bowel Disease (IBD) comprises two clinically and pathologically distinct chronic intestinal inflammatory diseases, ulcerative colitis (UC) and Crohn's disease (CD). Both diseases result from a dysregulated mucosal immune response to the commensal gut microbiota in genetically predisposed individuals. Because gut dysbiosis is a constant feature of both diseases, Fecal Microbiota Transplantation (FMT) has recently been investigated as a potential therapeutic strategy to restore a balanced microbiota composition in patients with IBD. There are five placebo-controlled randomized controlled trials (RCTs) in UC and several meta-analyses, which showed that treatment with FMT using material from multiple donors can lead to clinical and endoscopic remission in patients with mild-to-moderate UC and may thus double to triple the rate of remission compared with placebo (number needed to treat [NNT] ≈ 3-5). In contrast, evidence for CD is limited and inconsistent, with one promising pilot study being contrasted with a large multicenter induction trial that was stopped for futility. This review provides an update of the current molecular understanding of FMT-induced recovery of mucosal barrier function and inflammation control in intestinal inflammation (α-diversity restoration and subsequent donor strain engraftment, production of short-chain fatty acids and secondary bile acids, tryptophan-AhR signaling, IL-10-mediated induction of Tregs vs. suppression of Th17 cells and restoration of epithelial barrier function). The review also summarizes the current clinical evidence for the use of FMT in IBD, its safety, and the current regulatory status. It also describes recent developments in FMT, including the use of defined bacterial consortia, 'live biotherapeutic products' (LBPs), and donor-recipient pairing. Collectively, FMT provides evidence of principle for manipulating intestinal microbial ecosystems to treat immune-mediated intestinal inflammation.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Inflammatory Bowel Diseases/therapy/microbiology
*Gastrointestinal Microbiome
Animals
Dysbiosis/therapy

@article {pmid43028863,
year = {2026},
author = {Zhang, F and Lai, X and He, Z and Wang, S and Liu, S and Wang, X and Yan, L},
title = {Indigenous Soil Microbiota Shapes Bacillus subtilis-Mediated Biocontrol Against Potato Bacterial Wilt Revealed by Integrated Rhizosphere Microbiome and Metabolome Profiles.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43028863},
issn = {2223-7747},
abstract = {The inconsistent field performance of microbial biocontrol agents is often linked to resident soil microbiota, yet how indigenous microbiota influence Bacillus-mediated suppression of potato bacterial wilt remains insufficiently understood. In this study, sterilized and non-sterilized soils were used to evaluate how indigenous soil microbiota affect the biocontrol efficacy of Bacillus subtilis against Ralstonia solanacearum. Disease development, pathogen abundance, B. subtilis abundance, full-length 16S rRNA amplicon sequencing, and untargeted metabolomics were integrated to characterize rhizosphere microbial and metabolic responses. Soil microbial background strongly influenced disease progression and Bacillus performance. Under sterilized-soil conditions, R. solanacearum abundance remained 3-5-fold higher and disease severity increased more rapidly, whereas in non-sterilized soil, B. subtilis significantly reduced disease index and pathogen abundance. Microbiome analyses showed that sterilized soil was associated with limited Bacillus-mediated pathogen buffering, whereas non-sterilized soil supported the enrichment of potentially beneficial taxa, including Burkholderia, Devosia, and Rhizobium, together with soil-context-dependent microbial association patterns and shifts in predicted functional potential. Metabolomic profiling further revealed that Bacillus-associated metabolic profiles were highly soil-context-dependent, with low overlap between sterilized and non-sterilized soils under Bacillus treatment, as indicated by a Jaccard similarity of 0.059. In non-sterilized soil, Bacillus treatment was associated with defense-related metabolic profiles involving aromatic defense-related compounds and metabolites associated with antimicrobial activity and systemic resistance, whereas sterilized soil showed stronger damage-compensation-associated metabolic patterns. These findings suggest that indigenous soil microbiota may shape the ecological expression of B. subtilis-mediated biocontrol and highlight the importance of considering resident microbial backgrounds for potato bacterial wilt biocontrol.},
}

@article {pmid43028950,
year = {2026},
author = {Punja, ZK},
title = {Next-Generation Sequencing Reveals the Total Yeast and Mold Species Present in Greenhouse-Grown Cannabis Inflorescences-Implications for Quality Control.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43028950},
issn = {2223-7747},
support = {ALLRP 571270-21//Natural Sciences and Engineering Research Council of Canada/ ; URACP 19-212//BC Ministry of Agriculture/Agriculture and Agri-Food Canada/ ; },
abstract = {Next-generation sequencing (NGS) was conducted to determine the composition of the fungal and yeast species (mycobiome) within inflorescences of seven THC-containing genotypes of cannabis (Cannabis sativa L.). They were grown under conventional hydroponic cultivation or under organic production in commercial greenhouses. Up to 26 fungal and yeast species were identified from DNA sequence homologies to representative species in databanks. The mycobiome composition varied according to cultivation method, cannabis genotype, and post-harvest drying. Highest numbers of total fungal reads were present in organically grown inflorescences. Stem tissues supporting the inflorescences contained up to 50% of total fungal reads. Using scanning electron microscopy, fungal spore-like structures and mycelium were observed within the stem tissues. The genera represented by >1% of total fungal reads within inflorescences were Alternaria, Aspergillus, Botrytis, Candida, Fusarium, Penicillium, Trichoderma and Rhizophagus. Post-harvest drying of the inflorescences reduced total fungal reads by 50-65%, depending on cannabis genotype and fungal species. Detached trichome glands subjected to NGS analysis revealed a range of air-disseminated fungi, including Penicillium, Fusarium, Beauveria, Trichoderma, Aspergillus, Botrytis, Alternaria and Aureobasidium. Spore-like structures were observed attached to the external surfaces of glandular trichomes using scanning electron microscopy. The occurrence of mycotoxin-producing species of Aspergillus was rare, while species of Alternaria, Fusarium and Penicillium, recognized as potential mycotoxin producers, were more frequent. The most prevalent fungal species reads among 12 dried cannabis samples were Penicillium chrysogenum, P. citrinum and Alternaria spp.; Botrytis and Fusarium spp. were also present in six samples. The use of biological control products containing Trichoderma and Beauveria during flower development increased fungal reads of these species in fresh inflorescences, with some carry-over into dried samples. The mycorrhizal fungus Rhizophagus irregularis was detected in inflorescence tissues. Reads of a number of previously unreported fungal species were present within inflorescences at very low frequencies. Their origins may be from the surrounding environment or the growing substrate used during cannabis cultivation. Human DNA was found in a number of dried samples, possibly from physical handling of post-harvest inflorescences. These results indicate the diversity and prevalence of certain genera of fungi/yeasts in greenhouse-cultivated cannabis inflorescences.},
}

@article {pmid43028980,
year = {2026},
author = {Lei, J and Lv, N and Liu, P and Liu, C and Peng, G},
title = {Taxonomic Guilds, Action Mechanisms, and Agronomic Deployment of Maize Rhizosphere Microbiota for Yield Enhancement: Unraveling G×M×E Interactions and Translational Barriers via Multi Omics.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43028980},
issn = {2223-7747},
support = {CSTB2025TIAD-LYKJXZLHGGXO004//Chongqing Key Special Project of Technological Innovation and Application Development/ ; NW-CSTB2025NYKJGGXMLSGXZYLXMX0001//the Agricultural Science and Technology R&D Program of Chongqing/ ; WSWZZ 2020004//Chongqing Entomopathogenic Fungi Strain Resource Bank/ ; },
abstract = {Maize (Zea mays L.) productivity is increasingly constrained by edaphic stressors-including soil salinization, drought, and acidification-posing mounting threats to global food security. Plant growth-promoting microorganisms (PGPM) offer a sustainable alternative to synthetic fertilizers, yet despite their pronounced performance under controlled laboratory settings, their beneficial effects often prove inconsistent in open-field environments, largely due to spatial heterogeneity and genotype-specific responses. Herein, we present a comprehensive synthesis of the core microbial guilds that have been robustly associated with maize yield enhancement. The mechanisms underlying these effects are examined across several dimensions, including biological nitrogen fixation, phosphate and potassium solubilization, phytohormone production, ethylene regulation, stress tolerance, and rhizosphere colonization. Genomic, transcriptomic, metagenomic, and metabolomic data are integrated to construct an interaction network between maize and rhizosphere microbes. We identify the genotype-by-microbiome-by-environment (G×M×E) interplay as the principal bottleneck hampering field-scale translational success. To address this issue, three priorities are proposed: (i) designing synthetic microbial consortia, (ii) using multi-omics to examine mechanisms, and (iii) developing tools for site-specific deployment. In conclusion, these sections provide a framework for developing more reliable microbial inoculants for maize.},
}

@article {pmid43028984,
year = {2026},
author = {Wang, D and Liao, J and Chen, T and Cai, Z and Chen, Z and Wang, Q},
title = {RXLR-Mediated Delivery of Exogenous CRr Protein Reduces Clubroot in Tumorous Stem Mustard and Reshapes the Rhizosphere Microbiome.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43028984},
issn = {2223-7747},
support = {CSTB2023NSCQ-LZX0074//Chongqing Municipality Natural Science Foundation Innovation and Development Joint Fund/ ; CQYC20220302547//Chongqing Talent Plan "Lump-sum Funding System" Project/ ; },
abstract = {Clubroot, incited by the obligate biotrophic protist Plasmodiophora brassicae, poses a severe threat to cruciferous crop production worldwide. Building on the concept of exogenous NLR protein delivery, we tested whether a bacterially expressed CRr protein (a recombinant Crr1a protein fused with an RXLR motif) could confer protection against clubroot in tumorous stem mustard (Brassica juncea var. tumida). Seedling roots were exposed to a crude lysate harboring the RXLR-Crr1a chimera, after which the fate of the protein and its downstream consequences were monitored across molecular, ecological, and metabolic levels. Time-resolved fluorescence imaging demonstrated that the recombinant signal became broadly distributed throughout the root system within a 24 h window, concomitant with a marked alleviation of disease severity. An empty vector control (equal protein, pET-28a(+) lysate) showed no significant protection versus the pathogen-only control (p > 0.05), suggesting that the observed protection is associated with the CRr protein lysate rather than general bacterial components. At the microbial level, the treatment fostered a more interconnected rhizosphere co-occurrence network and selectively promoted taxa, recognized as beneficial bacteria. At the metabolic level, several defense-associated compounds were elevated, among them jasmonic acid methyl ester, (2R)-2-hydroxyphenethylglucosinolate, 8-hydroxyluteolin 4'-methyl ether 8-glucuronide, and 4-hydroxyglucobrassicin. Furthermore, soil populations of beneficial bacteria including the Gram-positive genera Bacillus and Priestia exhibited strong positive associations with host defense metabolites. Collectively, these findings support a model in which externally supplied CRr protein lysate induces a response that can be observed at the metabolite and microbiome levels via rapid protein dissemination. This work lays a conceptual foundation for protein-based, microbiome-oriented management of soil-borne diseases without genetic modification of the crop.},
}

@article {pmid43029048,
year = {2026},
author = {Wu, Y and Wang, F and Liu, S and Dai, T and Deng, J and Jiang, L and Yimingniyazi, A and Wang, S},
title = {Density-Dependent Changes in Root Exudates, Rhizosphere Microbes, and Soil Metabolites of Solanum rostratum.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43029048},
issn = {2223-7747},
support = {32460684//National Natural Science Foundation of China/ ; 2023D01B37//Natural Science Foundation of the Xinjiang Uygur Autonomous Region/ ; XKLEAEEEO-09//Xinjiang Key Laboratory for Ecological Adaptation and Evolution of Extreme Environment Organisms/ ; //Forage Germplasm Resources Survey in Xinjiang/ ; },
abstract = {Intraspecific competition shapes high-density monodominant communities of invasive plants, but how density is associated with rhizosphere microbial reassembly and soil metabolite accumulation via root exudates remains unclear. We established four planting densities (1, 3, 5, and 10 plants per pot) and integrated growth and photosynthetic physiology, root exudate metabolomics, rhizosphere metagenomics, and soil metabolomics using Mantel tests and variable-level correlation analysis. Increasing density reduced all traits except plant height, which showed a slight, non-significant increase followed by a significant decrease. Root exudates shifted from phenolic acid/terpenoid dominance at low density to sugar/peptide dominance at high density. Low-density-enriched bacterial genera were positively correlated with biomass, whereas high-density-enriched genera (e.g., Ilumatobacter, Allosphingosinicella) were negatively correlated. Soil metabolites such as Glutarate Semialdehyde and Sutherlandin D were negatively correlated with biomass, root traits, and photosynthesis. Mantel tests showed strong correlations between plant phenotypes and root exudates (r = 0.80) and between exudates and soil metabolites (r = 0.83). Variable-level analysis linked phenolic acid exudates to putatively growth-associated bacteria (e.g., Flavitalea, Blastococcus) and sugar/peptide exudates to putatively stress-adapted bacteria (e.g., Allosphingosinicella, Ilumatobacter), which were positively correlated with Glutarate Semialdehyde and Sutherlandin D accumulation. These results indicate that density-associated exudate changes synchronized with rhizosphere microbial reassembly and soil metabolite accumulation, forming an "exudate-microbe-metabolite" cascade. This cascade may buffer against high-density intraspecific competition and help explain monodominant community formation in invaded ranges.},
}

@article {pmid43029077,
year = {2026},
author = {Fernández-Pozo, LF and Rodríguez-González, MA},
title = {Effects of Irrigation Regime and Seasonal Dynamics on the Rhizosphere Microbiome on Calcaric Cambisols in Western Iberian Vineyards: An Observational Study Across Seasons.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43029077},
issn = {2223-7747},
support = {GR24153//Government of Extremadura/ ; },
abstract = {Understanding how management and seasonality are associated with the soil microbiome is relevant for the sustainability of Mediterranean viticulture. This observational study compared the rhizosphere microbiome of rainfed and irrigated 'Pardina' vineyards on Calcaric Cambisols (Tierra de Barros, Extremadura, Spain) in five sampling campaigns (spring 2024-spring 2026) using 16S rRNA gene and ITS1 amplicon metabarcoding. The 30 soil samples were aggregated into ten community profiles per marker (five campaigns × two management), so inference is exploratory and limited by the absence of plot-level replication. Fungal communities in irrigated vineyards showed lower observed genus richness (median 180 vs. 297), Shannon diversity (3.05 vs. 3.84) and evenness than rainfed ones, with the same direction in all five campaigns, and a tendency toward higher dominance of a few genera (Berger-Parker 19.3% vs. 11.9%; not significant after correction), whereas prokaryotic richness and Shannon diversity did not differ consistently. Bray-Curtis PERMANOVA indicated a modest association between management and prokaryotic composition (R[2] = 0.237, p = 0.048), which was not robust to permutations restricted within campaigns, and no detectable association for fungi (R[2] = 0.151, p = 0.269); both results were sensitive to the inclusion of the spring 2026 campaign. The season and its interaction with management were not significant. Soil pH, available phosphorus and organic carbon differed between managements and planting density differed by design, so the patterns cannot be attributed to irrigation itself. The bacteria-to-fungi ratio, a sequencing-derived index, is reported descriptively only. These results identify candidate taxa and hypotheses to be tested in replicated experiments that include soil moisture and functional measurements.},
}

@article {pmid43029082,
year = {2026},
author = {Islam, MM and Hwang, Y and Choi, Y and Kang, KS},
title = {Cross-Regional Reanalysis of 16S rDNA Amplicon Sequence Data Reveals Core Taxa and Regional Modular Dynamics in the Panax ginseng Rhizosphere Bacterial Community.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43029082},
issn = {2223-7747},
support = {No. RS-2025-02263193//National Research Foundation (NRF), korea/ ; RS-2025-13642970//National Research Foundation (NRF), korea/ ; 26Z9061//Korea Institute of Science and Technology/ ; RS-2026-25596850//National Research Foundation of Korea/ ; },
abstract = {The rhizosphere microbiome plays a crucial role in the development, health, and therapeutic properties of Panax ginseng. Therefore, we evaluated the spatial trends in bacterial communities using a comprehensive reanalysis of 359 sequenced rhizosphere samples from seven NCBI Sequence Read Archive BioProjects. The SILVA reference database was used to compare the Chinese and Korean sequencing datasets, focusing on quality filtering, denoising, amplicon sequence variants, and taxonomy assignment. The bacterial community structure was characterized, and differentially abundant taxa were identified using the Kruskal-Wallis test with false discovery rate correction. In addition, based on the detected bacterial taxa, potential ecological traits were contextually interpreted to provide insight into their potential ecological significance. Despite regional and technical variations, 37 bacterial taxa consistently emerged as conserved core microbiome members. Regional analyses revealed distinct bacterial drivers, such as Ligilactobacillus, Romboutsia, Nitrospira, and Bradyrhizobium in the Korean samples and Holophaga and Arachidicoccus in the Chinese samples. Putative functional annotations showed that plant-associated defense mechanisms, nutrient mobilization, and carbon cycling varied geographically. Overall, these findings indicate that although a conserved core community exists, regional differences may influence the composition, functional potential, and ecological relationships of the P. ginseng rhizosphere.},
}

@article {pmid43029102,
year = {2026},
author = {Xiao, O and Ma, B and Dai, X and Chen, J and Kong, Z},
title = {Dynamics of Rhizosphere Microbial Communities and Bioactive Compound Accumulation in Wild-Simulated Astragalus mongholicus Across Different Cultivation Years.},
journal = {Plants (Basel, Switzerland)},
volume = {15},
number = {21},
pages = {},
pmid = {43029102},
issn = {2223-7747},
support = {CARS-20//China Agriculture Research System of MOF and MARA/ ; 2026FRF05002//Key Research and Development Program of Ningxia/ ; 2026FRG05009//Key Research and Development Program of Ningxia/ ; },
abstract = {Knowledge regarding the structure and distribution patterns of rhizosphere microbial communities of Astragalus mongholicus (A. mongholicus) under wild-simulated cultivation remains limited. This study investigated how cultivation duration affects soil properties, microbial communities, and bioactive compound accumulation, as well as the relationships among these factors. High-throughput sequencing of the 16S rRNA and ITS regions was performed to profile bacterial and fungal communities in rhizocompartments of 1-4-year-old A. mongholicus. Meanwhile, soil physicochemical properties and bioactive compounds were quantified. Fungal community diversity in the rhizosphere of A. mongholicus varied across cultivation years, whereas bacterial community diversity showed a comparatively weaker response. The relative abundances of the potentially beneficial taxa Mortierellomycota and Mortierella in rhizosphere soil gradually declined with increasing cultivation age. Soil nutrient-related variables (OM, OC, P, and NH4[+]-N) were the main drivers shaping microbial community composition. Bioactive compound contents also fluctuated across cultivation years. Microbial genera including Mortierella, Pseudomonas, Bacillus, and the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium clade may be closely associated with the accumulation of bioactive compounds in A. mongholicus. These findings suggest that cultivation duration reshaped rhizosphere communities and bioactive compound accumulation in A. mongholicus. Soil nutrient availability and beneficial microbes were closely associated with these changes, providing insights for microbiome-informed quality improvement.},
}

@article {pmid43029242,
year = {2026},
author = {Senn, R and Pugin, B and Merk, VM and Mujezinovic, D and Zünd, J and Boonen, G and Lacroix, C and Butterweck, V},
title = {Gastrointestinal Stability and Microbiota-Mediated Deglycosylation of Triterpene Glycosides from Cimicifuga racemosa Extract Ze 450.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {21},
pages = {},
pmid = {43029242},
issn = {1420-3049},
mesh = {*Cimicifuga/chemistry ; Humans ; *Glycosides/chemistry/metabolism ; *Triterpenes/chemistry/metabolism ; Female ; *Plant Extracts/chemistry/pharmacology ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Glycosylation ; Biotransformation ; *Gastrointestinal Tract/microbiology ; },
abstract = {Triterpene glycosides (TTGs) are characteristic constituents of Cimicifuga racemosa extract Ze 450 and may contribute to its pharmacological effects in the treatment of menopausal symptoms. This exploratory study investigated their gastrointestinal stability, transformation during incubation with human fecal microbiota, and potential effects on microbial community composition and short-chain fatty acid (SCFA) production. The stability of 23-epi-26-deoxyactein was assessed during simulated oral and gastric digestion using the INFOGEST protocol. Microbiota-associated biotransformation of actein, 23-epi-26-deoxyactein, cimigenol-3-β-D-xyloside, and cimigenol-3-α-L-arabinoside was subsequently examined during 48 h anaerobic ex vivo cultivation with fecal microbiota from eight female donors. 23-Epi-26-deoxyactein remained largely stable during simulated oral and gastric digestion. During fecal incubation, all investigated TTGs were depleted and the corresponding aglycones were detected. Quantification of the 23-epi-26-deoxyactein aglycone revealed marked donor-dependent differences, indicating substantial interindividual variability in TTG biotransformation. Individual TTGs had little effect on microbial community composition or SCFA profiles, whereas Ze 450 induced a small but significant shift in overall community structure without substantially affecting SCFA production. These findings demonstrate extensive microbiota-mediated TTG deglycosylation and highlight marked interindividual variability in TTG metabolism, providing a rationale for further investigation of microbiome-dependent differences in the pharmacological fate of Ze 450.},
}

*Cimicifuga/chemistry
Humans
*Glycosides/chemistry/metabolism
*Triterpenes/chemistry/metabolism
Female
*Plant Extracts/chemistry/pharmacology
Feces/microbiology
*Gastrointestinal Microbiome/drug effects
Glycosylation
Biotransformation
*Gastrointestinal Tract/microbiology

@article {pmid43029288,
year = {2026},
author = {Szydłowska, A and Sionek, B and Łepecka, A},
title = {Potential Applications of Next-Generation Probiotics in the Development of Functional Food Products.},
journal = {Molecules (Basel, Switzerland)},
volume = {31},
number = {21},
pages = {},
pmid = {43029288},
issn = {1420-3049},
mesh = {*Probiotics ; Humans ; *Functional Food ; Animals ; },
abstract = {Next-generation probiotics (NGPs), isolated from the human gut microbiome, represent a breakthrough direction in the development of precision functional foods and targeted biotherapeutics. This review article presents the current state of knowledge regarding the classification, mechanisms of action, and technological and regulatory challenges associated with the application of NGPs in functional food design. Representative commensal species (Akkermansia muciniphila, Faecalibacterium prausnitzii, Anaerobutyricum hallii, Prevotella copri, Clostridium butyricum and Bacteroides fragilis, Roseburia spp.) were analyzed to evaluate their capacity to maintain intestinal epithelial integrity, their efficiency in short-chain fatty acid (SCFA) synthesis, and their modulation of host immune responses. Their commercial use remains limited because most NGP strains are strict anaerobes that readily lose viability when exposed to oxygen, processing stress, or digestive fluids. Regulatory frameworks classify NGPs as live biotherapeutic products (LBPs) or Novel Foods, requiring rigorous safety evaluation and clinical trials. The effective implementation of NGP formulations in functional food production remains strictly dependent on the harmonization of global legislative criteria and advancements in the bioengineering of protective delivery systems, capable of maintaining cellular integrity and ensuring the biological activity of strains at the point of consumption of the final product.},
}

*Probiotics
Humans
*Functional Food
Animals

@article {pmid43030090,
year = {2026},
author = {Crivei, IC and Ratu, RN and Veleșcu, ID and Balint, AB and Lipșa, FD and Stoica, F and Crivei, LA},
title = {Food Additives as Microbiome-Active Dietary Exposures: Mechanisms, Host Susceptibility, and an Operational Case for Microbiome-Inclusive Risk Assessment.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030090},
issn = {2072-6643},
mesh = {Humans ; *Food Additives/adverse effects ; Risk Assessment ; Animals ; *Dietary Exposure/adverse effects ; *Microbiota/drug effects ; *Gastrointestinal Microbiome/drug effects ; Disease Susceptibility ; },
abstract = {Food additives are defining components of ultra-processed foods, yet microbiome-related effects remain largely outside routine safety assessment. This review evaluates evidence for six additive classes across four pathways-microbial community changes, altered microbial metabolites, mucus-epithelial barrier disruption, and immune modulation-and examines how these findings could inform microbiome-inclusive risk assessment. Mechanistic, translational, and epidemiological evidence was organized using a five-tier hierarchy: in vitro, ex vivo, animal, observational, and controlled human studies. Chronic-disease associations were graded across six domains by two raters using explicit criteria, with sensitivity analysis. Evidence was then translated into a tiered, decision-gated assessment protocol, illustrated with carboxymethylcellulose and back-tested against carrageenan, acesulfame K, and titanium dioxide, which return three different protocol outcomes. Non-nutritive sweeteners and emulsifiers have the strongest direct human and ex vivo evidence, including microbiome-dependent interindividual responses, although null and discordant trials remain. Gastrointestinal and metabolic outcomes received the highest support, cardiovascular associations were intermediate, and autoimmune, neurological, and psychiatric links remained preliminary. Metabolic and cardiovascular epidemiology relied largely on NutriNet-Santé, with modest hazard ratios (generally 1.03-1.15 per exposure increment) and indirect exposure estimation. Recent additive-mixture analyses from the same cohort were also considered. Food additives can act as context-dependent, microbiome-active exposures. Current evidence supports considering microbiome composition, barrier-integrity, and immune endpoints in additive safety evaluation, while causal links with most chronic-disease outcomes remain unproven.},
}

Humans
*Food Additives/adverse effects
Risk Assessment
Animals
*Dietary Exposure/adverse effects
*Microbiota/drug effects
*Gastrointestinal Microbiome/drug effects
Disease Susceptibility

@article {pmid43030098,
year = {2026},
author = {Albani, G and Capodaglio, P and Giardini, M and Modaffari, G and Ranjani Chellamuthu, V and Chao, YX and Jayaraman, A and Albani, S and Tan, EK},
title = {Gut Microbial Levodopa Metabolism and Constipation in Prodromal and Established Parkinson's Disease.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030098},
issn = {2072-6643},
support = {//Ministry of Health/ ; VRC is supported with SingHealth Duke-NUS Academic Medicine Research Grant AM/SU114/2025 (SRDUKAMR25S4). Institutional funding support to SA from Duke-NUS and SingHealth AMC core funding is gratefully acknowledged. This research is supported by A*STAR und//Duke-NUS Medical School/ ; },
mesh = {Humans ; *Parkinson Disease/drug therapy/complications/microbiology/metabolism ; *Levodopa/metabolism ; *Constipation/microbiology/etiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Dopamine/metabolism ; Prodromal Symptoms ; *Antiparkinson Agents/metabolism ; },
abstract = {Background: Constipation can precede the motor diagnosis of Parkinson's disease (PD), but its mechanisms are multifactorial. Gut bacteria can metabolize administered levodopa (LD), and enteric dopamine receptors participate in the regulation of motility. These observations motivate, but do not establish, a connection between microbial LD metabolism and constipation. Evidence: Bacterial tyrosine decarboxylase (TDC) converts LD to dopamine in biochemical and animal systems. Human studies associate fecal TDC abundance with some treatment and pharmacokinetic variables, but gene abundance does not measure enzyme activity. A longitudinal PD cohort found an inverse association between constipation severity and TDC abundance in one model, highlighting the need to consider medication effects and reverse causation. Microbiome alterations in risk-enriched populations do not demonstrate increased TDC activity before PD diagnosis. Hypothesis: In a subset of untreated individuals at increased risk of PD, sufficient luminal endogenous L-DOPA might permit microbial dopamine production that influences intestinal transit, provided that the resulting dopamine reaches relevant receptors at effective concentrations. Endogenous substrate availability, anatomical access, and the net balance of dopamine production and clearance are unresolved. After LD treatment begins, a larger exogenous substrate supply creates a distinct setting for drug-microbe interactions. Conclusions: The proposed continuum is conditional and requires biochemical and functional validation before human biomarker development. We propose substrate tracing, comparisons of TDC-positive and TDC-deficient bacteria, receptor-specific testing, and longitudinal gastrointestinal phenotyping. Current evidence does not justify TDC-directed dietary prevention of PD or clinical prediction from fecal TDC abundance alone.},
}

Humans
*Parkinson Disease/drug therapy/complications/microbiology/metabolism
*Levodopa/metabolism
*Constipation/microbiology/etiology/metabolism
*Gastrointestinal Microbiome/physiology
Animals
Dopamine/metabolism
Prodromal Symptoms
*Antiparkinson Agents/metabolism

@article {pmid43030130,
year = {2026},
author = {Chung, DH and Baek, J and Park, SP and Kim, SH and Jee, D},
title = {Probiotic Supplement Use and Diabetic Retinopathy in Korean Adults with Diabetes: A Nationwide Population-Based Study.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030130},
issn = {2072-6643},
support = {grant no. RS-2025-02218330 and RS-2025-25417985//Patient-Centered Clinical Research Coordinating Center (PACEN), funded by the Ministry of Health & Welfare, Republic of Korea/ ; },
mesh = {Humans ; *Probiotics/administration & dosage ; *Diabetic Retinopathy/epidemiology/prevention & control ; Female ; Male ; Middle Aged ; Republic of Korea/epidemiology ; *Dietary Supplements ; Adult ; Prevalence ; Aged ; Nutrition Surveys ; Cross-Sectional Studies ; Risk Factors ; },
abstract = {Background/Objectives: Experimental studies implicate the gut microbiome in diabetic retinopathy (DR), but population-based data on probiotic supplementation and DR are lacking. We examined this association in Korean adults with diabetes. Methods: We analyzed 2071 adults with diabetes in the Korea National Health and Nutrition Examination Survey 2018-2021 with graded fundus photographs and a product-level dietary supplement interview. We used survey-weighted logistic regression (prespecified) and Poisson regression (added after the initial analysis) estimated odds ratios (ORs) and prevalence ratios (PRs), adjusted for age, sex, hypertension, smoking, and household income (Model 1), and additionally for diabetes duration and glycated hemoglobin (HbA1c) (Model 2, primary), with further adjustment for clinical, lifestyle, and dietary factors. Results: Probiotic supplements were used by 10.4% of participants. Weighted DR prevalence was 11.0% among users and 21.1% among non-users (Model 2 PR 0.57, 95% CI 0.36-0.90; OR 0.49, 95% CI 0.28-0.86; 27 exposed cases; fully adjusted PR 0.59, 95% CI 0.37-0.95). In exploratory analyses, compared with non-use, the PRs were 0.76 (95% CI 0.45-1.29; not statistically significant) for use of <1 year and 0.28 (95% CI 0.13-0.62) for use of ≥1 year. No probiotic user had vision-threatening DR, compared with 3.9% of non-users (unadjusted design-based p = 0.024), a descriptive observation that does not demonstrate a protective effect. Use of any non-probiotic supplement was not associated with DR (PR 0.92), although vitamin C and vitamin A/lutein supplements showed inverse associations of similar magnitude. Conclusions: Probiotic supplement use was associated with a lower prevalence of DR among Korean adults with diabetes. These cross-sectional findings are consistent with, but do not establish, a role of the gut-retina axis in DR and require confirmation in prospective studies.},
}

Humans
*Probiotics/administration & dosage
*Diabetic Retinopathy/epidemiology/prevention & control
Female
Male
Middle Aged
Republic of Korea/epidemiology
*Dietary Supplements
Adult
Prevalence
Aged
Nutrition Surveys
Cross-Sectional Studies
Risk Factors

@article {pmid43030131,
year = {2026},
author = {García-Ramírez, CC and Campo, FM and Ortíz-González, JE and González-Heredia, T and Cueto-Manzano, AM},
title = {Gut Microbiota Dysbiosis in Advanced Chronic Kidney Disease and Kidney Transplantation: A Narrative Review of Pathophysiological Mechanisms, Implications for Nutritional Status, and Biotic Interventions.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030131},
issn = {2072-6643},
support = {09 B5 61 61 2800/2025/642, and registration number R-2025-785-001//Mexican Social Security Institute/ ; },
mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Dysbiosis/physiopathology/microbiology/therapy ; *Nutritional Status ; *Gastrointestinal Microbiome/physiology ; *Renal Insufficiency, Chronic/microbiology/physiopathology/therapy/surgery ; Probiotics/administration & dosage/therapeutic use ; Prebiotics/administration & dosage ; Immunosuppressive Agents/adverse effects ; Animals ; },
abstract = {Chronic kidney disease (CKD) is a serious public health issue affecting 10% of the global population. CKD is associated with intestinal dysbiosis, characterized by a reduction in saccharolytic bacteria and an increase in proteolytic genera that produce uremic toxins. This may promote intestinal barrier impairment ("leaky gut" syndrome), chronic low-grade inflammation, and protein-energy wasting (PEW), although most of the supporting evidence is observational. Kidney transplantation (KT) improves survival but may not fully reverse dysbiosis. KT recipients are exposed to residual uremia, use of perioperative antibiotics, and chronic immunosuppressive regimens. Drugs such as mycophenolate mofetil can cause gastrointestinal toxicity and reduced intake due to diarrhea or enteropathy, whereas corticosteroids and calcineurin inhibitors induce hyperphagia, hypomagnesemia, and insulin resistance. These factors may lead to a spectrum of complications ranging from persistent PEW in the early post-transplant period to a higher prevalence of weight gain and obesity, sarcopenia, and post-transplant diabetes. Furthermore, the microbiota may modulate pharmacological responses; in experimental and small clinical studies, genera such as Faecalibacterium have been linked to alterations in the metabolism of tacrolimus, potentially altering its therapeutic levels and the risk of nephrotoxicity or rejection. Interventions using biotics (prebiotics, probiotics, and synbiotics) are emerging as a potential adjuvant strategy to restore eubiosis and mitigate PEW. In non-dialysis and dialysis CKD patients, some biotics have been reported to reduce uremic toxins and inflammatory cytokines (IL-6, TNF-α), although results are heterogeneous. However, there is no evidence available regarding its ability to improve nutritional status following a KT. Safety data are limited, although biotic interventions are generally considered safe. Future prospective studies are required to confirm their efficacy and immunological safety, as well as any possible association with infectious adverse events.},
}

Humans
*Kidney Transplantation/adverse effects
*Dysbiosis/physiopathology/microbiology/therapy
*Nutritional Status
*Gastrointestinal Microbiome/physiology
*Renal Insufficiency, Chronic/microbiology/physiopathology/therapy/surgery
Probiotics/administration & dosage/therapeutic use
Prebiotics/administration & dosage
Immunosuppressive Agents/adverse effects
Animals

@article {pmid43030137,
year = {2026},
author = {Rodríguez-Arellano, SN and González-Gómez, JP and Aguirre-Sánchez, JR and Gomez-Gil, B and Barrón-Cabrera, E and Chaidez, C and Vergara-Jiménez, MJ},
title = {Targeted Modulation of the Gut Microbiota in Obesity: From Dietary Interventions to Bacteriophage-Based Precision Therapies.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030137},
issn = {2072-6643},
mesh = {Humans ; *Obesity/microbiology/therapy ; *Gastrointestinal Microbiome ; Dysbiosis/therapy/microbiology ; *Bacteriophages ; *Phage Therapy/methods ; Prebiotics/administration & dosage ; Probiotics ; Animals ; *Precision Medicine/methods ; Fecal Microbiota Transplantation ; Inflammation/microbiology ; },
abstract = {Obesity is a complex chronic disease associated with metabolic and inflammatory alterations in which the gut microbiota has emerged as an important contributing factor. Obesity-associated gut dysbiosis involves not only changes in microbial composition but also alterations in microbial functions and metabolites that may affect intestinal barrier integrity, immune regulation, adipose tissue metabolism, insulin sensitivity, and glucose homeostasis. Current microbiota-modulating strategies, including dietary interventions, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, can influence the gut microbial ecosystem; however, their effects are often highly variable among individuals and generally lack the specificity required to selectively target disease-associated bacterial populations. These limitations have increased interest in precision microbiota modulation, which aims to selectively modify microbial populations, functions, or products while minimizing unnecessary alterations to the remaining microbial community. In this context, bacteriophages represent a promising biological tool because of their ability to specifically target bacterial hosts, offering the possibility of selectively reducing bacterial populations associated with obesity-related metabolic and inflammatory disturbances. Experimental studies and early human trials have shown that bacteriophage-based interventions can modulate gut microbial communities and influence inflammatory responses, supporting their potential relevance to obesity-associated chronic low-grade inflammation. However, no published clinical trials specifically evaluating targeted bacteriophage therapy for obesity treatment were identified, and its efficacy for obesity management remains unestablished. Further research is needed to identify and validate bacterial targets, optimize phage selection and cocktail design, and evaluate phage stability, bacterial resistance, immunomodulatory effects, safety, and host-microbiota interactions before clinical translation can be considered.},
}

Humans
*Obesity/microbiology/therapy
*Gastrointestinal Microbiome
Dysbiosis/therapy/microbiology
*Bacteriophages
*Phage Therapy/methods
Prebiotics/administration & dosage
Probiotics
Animals
*Precision Medicine/methods
Fecal Microbiota Transplantation
Inflammation/microbiology

@article {pmid43030145,
year = {2026},
author = {Marelli, S and Girombelli, A and Formenti, P and Vetrone, F},
title = {Gut Failure as a Potential Unmeasured Modifier of Micronutrient Response in Critical Illness: A Structured Narrative Review of Absorption, Metabolism, and Immune Function.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030145},
issn = {2072-6643},
mesh = {Humans ; *Critical Illness/therapy ; *Micronutrients/deficiency/metabolism ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Dietary Supplements ; Intestinal Absorption ; Dysbiosis ; Gastrointestinal Tract/metabolism ; },
abstract = {BACKGROUND: Micronutrient abnormalities are frequent in critically ill patients and are associated with organ dysfunction, infection, and adverse outcomes. Yet randomized controlled trials of supplementation have largely failed to demonstrate a consistent mortality or organ-failure benefit. One possible contributor to this translational gap is a systematically under-characterized variable: gut failure. In critical illness, the intestinal barrier is disrupted, epithelial cell mass is depleted, transporter expression is impaired, the intestinal microvasculature exhibits severe dysfunction, and the microbiome undergoes profound dysbiosis. These alterations may collectively impair the absorptive, metabolic, and immunological functions upon which micronutrient homeostasis depends.

PURPOSE: This structured narrative review (SANRA-guided; 202 records) first outlines the epidemiology of micronutrient deficiencies in the ICU and defines gut failure as a biological entity distinct from ileus. It then traces the mechanistic pathways by which a dysfunctional gut disrupts key micronutrients and links this gut-micronutrient axis to immune dysregulation.

OVERVIEW: We critically appraise landmark ICU supplementation trials and examine whether the absence of gastrointestinal phenotyping, reliance on circulating surrogates of bioavailability, and neglect of microbiome-nutrient interactions may have contributed to heterogeneous or negative findings. Finally, we propose a hypothesis-generating, gut-integrated framework for future studies, comprising gut integrity stratification, microbiome phenotyping, phase-adapted timing and route selection, and microbiome restoration, to realign micronutrient interventions with the biology of the gut-microbiome-immune axis. Direct evidence that gut dysfunction modifies the response to supplementation is lacking.},
}

Humans
*Critical Illness/therapy
*Micronutrients/deficiency/metabolism
Gastrointestinal Microbiome
Intestinal Barrier Function
Dietary Supplements
Intestinal Absorption
Dysbiosis
Gastrointestinal Tract/metabolism

@article {pmid43030171,
year = {2026},
author = {Riskin, A and Iofe, A and Safadi, RZ and Tal, N and Gover, A},
title = {The Early Nutrition Paradox in Preterm and Intrauterine Growth Restricted (IUGR) Infants: A Critical Review of the Developmental Programming Hypothesis and the Limits of Its Evidence.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030171},
issn = {2072-6643},
mesh = {Humans ; *Fetal Growth Retardation/physiopathology ; Female ; Developmental Origins of Health and Disease ; *Infant, Premature/growth & development ; Infant, Newborn ; Pregnancy ; Animals ; *Infant Nutritional Physiological Phenomena ; Nutritional Status ; Infant ; Weight Gain ; Maternal Nutritional Physiological Phenomena ; Risk Factors ; *Premature Birth ; },
abstract = {Nutrition during early life may be an important determinant of long-term health. Preterm birth, affecting approximately 10% of deliveries worldwide, and intrauterine growth restriction (IUGR) are major perinatal conditions. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that early nutritional and environmental exposures shape adult disease risk. This narrative review synthesizes epidemiological, cohort, animal, and interventional evidence on early nutrition and long-term outcomes in these infants. Rapid weight gain has been associated with later obesity and cardio-metabolic risk; however, this does not show that the tempo of gain, rather than attained size, carries the risk, and catch-up growth after preterm birth or growth restriction supports neurodevelopment. Preterm birth has been associated with a 53% higher risk of ischemic heart disease, whereas IUGR confers overlapping but distinct risks. Hypothesized mechanisms include epigenetic modification, structural organ deficits, hormonal reprogramming, gut-microbiome dysbiosis, and oxidative stress. Because the human evidence is almost entirely observational and vulnerable to confounding and to over-adjustment for attained body size, these associations should be read as hypotheses rather than established causal effects. Individualized, guideline-based and responsive feeding strategies, with support for mothers to provide their own milk, are needed to optimize immediate outcomes while limiting lifelong disease susceptibility.},
}

Humans
*Fetal Growth Retardation/physiopathology
Female
Developmental Origins of Health and Disease
*Infant, Premature/growth & development
Infant, Newborn
Pregnancy
Animals
*Infant Nutritional Physiological Phenomena
Nutritional Status
Infant
Weight Gain
Maternal Nutritional Physiological Phenomena
Risk Factors
*Premature Birth

@article {pmid43030188,
year = {2026},
author = {Ortiz, P and Palacios, E and Moreno-Blanco, A and Ruiz-Rodríguez, A and Aguilera, M},
title = {Childhood Adiposity and Bisphenol Exposure Are Linked to Gut Dysbiosis, Altered Short-Chain Fatty Acid and Complex Carbohydrate-Degrading Profiles.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030188},
issn = {2072-6643},
support = {FIS Project PI24/00046//Instituto de Salud Carlos III/ ; FPU21/01004//Ministerio de Ciencia, Innovación y Universidades (MICIU)/ ; CN-SEM-2024-010//Sociedad Española de Microbiología (SEM)/ ; MCIN/AEI/10.13039/501100011033//Ministerio de Ciencia, Innovación y Universidades/ ; },
mesh = {Humans ; *Phenols/adverse effects/toxicity ; *Fatty Acids, Volatile/metabolism ; *Adiposity/drug effects ; *Benzhydryl Compounds/adverse effects/toxicity ; *Gastrointestinal Microbiome/drug effects ; Female ; *Dysbiosis/chemically induced/microbiology ; Child ; Child, Preschool ; Feces/chemistry/microbiology ; Bisphenol A Compounds ; Male ; *Carbohydrate Metabolism/drug effects ; *Endocrine Disruptors/adverse effects ; *Pediatric Obesity/microbiology ; },
abstract = {BACKGROUND: Dietary exposure to endocrine-disrupting chemicals is increasingly associated with pediatric adiposity and gut dysbiosis. Although short-chain fatty acids (SCFAs) are traditionally known for being involved in metabolic homeostasis, their contribution to energy harvesting remains controversial and under continuous debate.

METHODS: We conducted an integrative study of 100 children (aged 3-12 years) stratified by BMI and total body fat percentage, with bisphenol exposure assessed via nail matrix biomonitoring. Gut microbiota was profiled via amplicon gene sequencing, fecal SCFAs were quantified by GC-MS, and the genomic capacity for complex carbohydrate degradation was predicted using functional profiling tools.

RESULTS: Children with high body fat percentage exhibited higher fecal concentrations of acetate, butyrate, and propionate. High bisphenol levels were also positively associated with both increased adiposity and elevated fecal SCFA profiles. Integrative analyses identified a distinct microbiota-metabolic signature: obesity and high bisphenol exposure were linked to an expansion of specific taxa such as Blautia, Collinsella, and Catenibacterium, contrasting with a reduction in potential protective markers including Oscillospiraceae, Bacteroides plebeius, and Christensenellaceae R-7. Notably, key functional and gene-enzymatic profiling revealed an enriched carbohydrate-degrading potential within the adiposity and BPA-associated microbiota, consistent with enhanced fiber degradation, increased SCFA production, and greater predicted energy-extracting potential.

CONCLUSIONS: The co-occurrence of host metabolic and environmental factors together with the altered microbiome features, points towards a shift in microbial energy harvesting. The findings outline a correlative 'chemical obesogen-microbiome-adiposity' interplay, linking environmental xenobiotic exposure to specific microbial alterations and metabolic changes associated with pediatric fat accumulation.},
}

Humans
*Phenols/adverse effects/toxicity
*Fatty Acids, Volatile/metabolism
*Adiposity/drug effects
*Benzhydryl Compounds/adverse effects/toxicity
*Gastrointestinal Microbiome/drug effects
Female
*Dysbiosis/chemically induced/microbiology
Child
Child, Preschool
Feces/chemistry/microbiology
Bisphenol A Compounds
Male
*Carbohydrate Metabolism/drug effects
*Endocrine Disruptors/adverse effects
*Pediatric Obesity/microbiology

@article {pmid43030189,
year = {2026},
author = {Rao, A and Shalem, T and Batacan, R and Bajagai, YS and Briskey, D},
title = {Targeted Colostrum Bioactive Proteins Improve Gastrointestinal Symptoms and Modulate the Gut Microbiome: A Randomised Double-Blind Placebo-Controlled Trial.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030189},
issn = {2072-6643},
support = {//Maolac/ ; },
mesh = {Humans ; Double-Blind Method ; *Colostrum/chemistry ; Female ; Adult ; *Gastrointestinal Microbiome/drug effects ; Animals ; Middle Aged ; Male ; *Gastrointestinal Diseases/microbiology ; *Dietary Supplements ; Quality of Life ; Cattle ; Young Adult ; },
abstract = {BACKGROUND: Gastrointestinal (GI) symptoms such as indigestion, bloating and reflux are common and can negatively affect quality of life. Bovine colostrum is a rich source of nutrients and other bioactive constituents that has been shown to be beneficial for gut health.

METHODS: This 12-week, randomised, double-blind, placebo-controlled, 3-arm study aimed to evaluate the effects of MaolactinGI™, a proprietary bovine colostrum supplement, on upper GI symptoms and gut microbiome composition in healthy adults aged 18 years and older experiencing moderate GI discomfort. Participants completed a 4-week run-in period followed by an 8-week intervention period. Outcomes measured included changes in upper GI symptoms via the Gastrointestinal Symptom Rating Scale (GSRS), Gastroesophageal Reflux Disease Questionnaire (GerdQ), Bloating Symptoms Visual Analogue Scale (BSVAS), Digestion-associated Quality of Life Questionnaire (DQLQ), Bristol Stool Chart, intestinal permeability, faecal calprotectin, serum inflammatory markers, gut microbiome analyses, blood safety markers and adverse events.

RESULTS: Ninety eligible participants were allocated to either the high-dose (500 mg/day), low-dose (250 mg/day), or placebo groups, and data from 83 participants were analysed. The high-dose MaolactinGI™ group demonstrated statistically significant improvements in the total GSRS score and DQLQ score compared with placebo, suggesting a meaningful reduction in total symptom burden and improved quality of life. The improvements in GSRS were clinically meaningful in size, supporting the practical relevance of MaolactinGI™ for adults experiencing everyday upper GI discomfort. High-dose supplementation also preserved microbial richness relative to placebo (Chao1); exploratory within-group analyses further indicated enrichment of SCFA-associated commensal taxa. The intervention was well tolerated and demonstrated an acceptable safety profile.

CONCLUSIONS: These findings support the potential of targeted colostrum-derived bioactive protein fractions as a novel nutritional strategy for supporting GI health and microbiome balance.},
}

Humans
Double-Blind Method
*Colostrum/chemistry
Female
Adult
*Gastrointestinal Microbiome/drug effects
Animals
Middle Aged
Male
*Gastrointestinal Diseases/microbiology
*Dietary Supplements
Quality of Life
Cattle
Young Adult

@article {pmid43030191,
year = {2026},
author = {Kim, J and Nemet, I},
title = {Microbial Aromatic Amino Acid Metabolism in Cardiometabolic Disease.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030191},
issn = {2072-6643},
support = {/NH/NIH HHS/United States ; //Cleveland Clinic/ ; },
mesh = {Humans ; *Amino Acids, Aromatic/metabolism ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/metabolism ; Animals ; *Metabolic Diseases/microbiology/metabolism ; Host Microbial Interactions ; },
abstract = {The gut microbiota generates a diverse array of metabolites that influence host physiology. Among these, products of microbial metabolism of the aromatic amino acids tryptophan, phenylalanine, tyrosine, and histidine have emerged as important components of host-microbiome interactions relevant to cardiometabolic disease. This Review summarizes the microbial pathways, enzymes, and metabolic networks involved in aromatic amino acid metabolism and examines how dietary substrate availability, microbial community composition, microbial enzymatic capacity, host metabolism, and environmental factors influence metabolite production and biological activity. Microbiota-derived metabolites and host-microbial co-metabolites are associated with inflammation, vascular function, thrombosis, metabolic homeostasis, and host signaling pathways. Their biological effects are context-dependent and influenced by microbial pathway activity, host metabolic processing, tissue compartment, disease stage, and substrate availability. We further distinguish evidence derived from human observational studies, experimental metabolite administration, and demonstrated molecular mechanisms. Finally, we discuss strategies to modulate aromatic amino acid metabolism, including dietary interventions, functional foods, probiotics, fecal microbiota transplantation, microbial enzyme inhibitors, and metabolite sequestration approaches. Current evidence supports a framework linking dietary substrates, microbial enzyme activity, host responses, and cardiometabolic phenotypes, while highlighting important opportunities and challenges for developing precision microbiome-based therapeutics.},
}

Humans
*Amino Acids, Aromatic/metabolism
*Gastrointestinal Microbiome/physiology
*Cardiovascular Diseases/microbiology/metabolism
Animals
*Metabolic Diseases/microbiology/metabolism
Host Microbial Interactions

@article {pmid43030216,
year = {2026},
author = {Lin, M and Zhang, D and Li, S and Qu, Y and Cai, H},
title = {Planetary Health Diet-Compatible Food Substitutions in Obesity: Direct Evidence, Gut-Organ Mechanisms, and Translational Priorities.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030216},
issn = {2072-6643},
mesh = {Humans ; *Obesity/diet therapy/prevention & control ; *Diet, Healthy/methods ; Translational Research, Biomedical ; Gastrointestinal Tract ; Animals ; Diet, Plant-Based ; },
abstract = {Background: The Planetary Health Diet (PHD) is a plant-rich reference pattern rather than a validated obesity treatment. Its clinical value is difficult to interpret when direct PHD studies are combined with evidence from related dietary patterns, isolated substrates, and experimental models. Methods: This narrative review searched PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar through September 2026. Evidence was organized as direct PHD evidence, evidence from comparable dietary patterns or components, and predominantly experimental evidence. Human interventions and prospective cohorts were prioritized for clinical conclusions, while mechanistic studies were retained only when they clarified a PHD-compatible substitution or a testable gut-organ pathway. Results: Direct PHD evidence is mainly observational and supports associations with lower obesity risk, central adiposity, diabetes incidence, or metabolic dysfunction-associated steatotic liver disease; randomized studies more often test an energy-restricted program or a related plant-rich pattern. Component trials support effects on liver fat, appetite, barrier biology, and microbial function, but do not establish that a complete PHD produces the same effects. Short-chain fatty acids, bile acids, tryptophan metabolites, barrier signals, endocrine pathways, and redox/mitochondrial stress responses are plausible mediators with substantial tissue and person specificity; processing and food-safety exposures remain contextual modifiers rather than established PHD mechanisms. Conclusions: PHD-compatible food substitutions can be used as a clinically adaptable framework when energy intake, protein and micronutrient adequacy, cultural feasibility, affordability, and tolerability are addressed. Weight, waist, glycemia, hepatic risk, and muscle function should be evaluated separately. The complete PHD-microbiome-organ causal sequence and the added value of microbiome-guided personalization remain unproven.},
}

Humans
*Obesity/diet therapy/prevention & control
*Diet, Healthy/methods
Translational Research, Biomedical
Gastrointestinal Tract
Animals
Diet, Plant-Based

@article {pmid43030219,
year = {2026},
author = {Potu, BK and Arulkandan, A and Gopalakrishna, PK and Thanu, AS and Omar, NA and Nasr El-Din, WA and Vishnumukkala, T},
title = {Anatomical and Molecular Foundations of the Gut-Brain Axis in Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Translation.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030219},
issn = {2072-6643},
mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/metabolism/physiopathology ; Animals ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Brain/metabolism ; *Brain-Gut Axis/physiology ; Probiotics ; *Gastrointestinal Tract ; },
abstract = {Alzheimer's disease (AD) is a complex disease that involves systemic, vascular, and metabolic components affecting the brain, in addition to amyloid-beta (Aβ) and tau pathology. The microbiota-gut-brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system, involving neural, immune, endocrine, and metabolic pathways, has arisen as a mechanistically plausible and clinically relevant contributor to AD pathogenesis among these systemic contributors. This review integrates information from human observational research, preclinical transgenic and germ-free models, and clinical trials to assess how gut dysbiosis, intestinal barrier dysfunction, and microbial metabolites converge on amyloidogenic and tau-associated pathways. In preclinical models, disruption of intestinal barrier integrity is proposed to allow translocation of lipopolysaccharide and bacterial amyloids into the systemic circulation, activating Toll-like receptor and NLRP3 inflammasome signaling that may prime microglia and astrocytes towards a chronic neuroinflammatory state. Further, dysbiosis-mediated changes in short-chain fatty acid, tryptophan-kynurenine, and bile acid metabolism may influence amyloid precursor protein processing, microglial clearance capability, and tau phosphorylation. Preclinical germ-free and fecal-transfer investigations provide fundamental evidence for these pathways in rodent models, while human case-control and Mendelian randomization data indicate converging yet diverse associations that have not yet established underlying directionality in human disease. Therapeutic modulation of the axis has shown promising early phase and observational signals using probiotics, synbiotics, dietary pattern interventions, fecal microbiota transplantation and pharmacological targeting of the GLP-1 pathway; however, the phase 3 EVOKE and EVOKE+ trials of oral semaglutide did not meet their primary cognitive endpoint, and heterogeneity of trials, short follow-up, and inconsistent reporting of biomarkers currently preclude definitive conclusions. We conclude that the microbiota-gut-brain axis is a biologically plausible and therapeutically tractable component of AD pathophysiology, but translation from mechanistic plausibility to clinical utility will depend upon longitudinal, biomarker-anchored and adequately powered interventional trials in genetically and microbiologically diverse populations. Because diet is among the most readily modifiable determinants of gut microbiome composition and function, this review prioritizes dietary patterns, prebiotic fibers, and probiotic or synbiotic supplementation as practical strategies for investigating the microbiota-gut-brain axis in AD. Their disease-modifying efficacy remains unproven; therefore, mechanistic and pharmacological approaches are discussed as complementary avenues for informing future research.},
}

Humans
*Alzheimer Disease/therapy/microbiology/metabolism/physiopathology
Animals
*Gastrointestinal Microbiome/physiology
Dysbiosis
*Brain/metabolism
*Brain-Gut Axis/physiology
Probiotics
*Gastrointestinal Tract

@article {pmid43030234,
year = {2026},
author = {Amusat, O and Lee, SO},
title = {Beyond Bioavailability: Lutein Delivery Systems and the Shift Toward Precision Nutrition.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030234},
issn = {2072-6643},
mesh = {Humans ; *Lutein/administration & dosage/pharmacokinetics/chemistry ; Biological Availability ; *Drug Delivery Systems ; *Precision Medicine ; Animals ; Dietary Supplements ; },
abstract = {Lutein is a xanthophyll carotenoid and dietary pigment with an established role in ocular health and potential neuroprotective, hepatoprotective, cardiovascular, and anti-inflammatory effects. Despite this broad biological relevance, average lutein intake in Western populations remains approximately 1-2.2 mg/day, with no established RDI or RDA, while oral bioavailability is limited under typical dietary conditions. Delivery systems, including lipid-based systems, biopolymer matrices, colloidal nanocarriers, and stimuli-responsive smart platforms, have emerged as practical strategies to improve lutein stability, protect it during gastrointestinal transit, and enhance bioaccessibility and systemic exposure. However, genetic variation in uptake-related genes, including SCARB1 and CD36, alongside gut microbiome composition and body composition, may contribute to inter-individual variability in lutein response. Most existing reviews have examined lutein's health effects, encapsulation, and delivery systems; few have addressed whether formulation performance differs meaningfully among individuals. This review integrates lutein's chemistry, biological activity, and delivery systems, and considers how formulation design might be matched to individual absorption profiles rather than simply improving average bioavailability across a population. It distinguishes demonstrated delivery outcomes from proposed personalized applications and highlights the human evidence needed to validate this approach.},
}

Humans
*Lutein/administration & dosage/pharmacokinetics/chemistry
Biological Availability
*Drug Delivery Systems
*Precision Medicine
Animals
Dietary Supplements

@article {pmid43030255,
year = {2026},
author = {Han, R and Yang, Q and Sun, Z and Mao, D and Ding, W and Wang, Y and Ji, H and Wang, T},
title = {Immunoactive Tripeptide RMK Alters T-Cell Subset Proportions and Remodels the Gut Microbiome-Metabolite Axis in S180 Tumor-Bearing Mice.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030255},
issn = {2072-6643},
mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Sarcoma 180/drug therapy/immunology/metabolism ; *T-Lymphocyte Subsets/drug effects/immunology ; *Oligopeptides/pharmacology ; Thymus Gland/drug effects/pathology ; },
abstract = {BACKGROUND: Immunoactive peptides are emerging as safe oral immunomodulators, but whether a single tripeptide can alter T-cell subsets and the gut microbiome-metabolite axis is unclear.

METHODS: The synthetic tripeptide RMK (Arg-Met-Lys; HPLC purity > 98%) was given orally once daily to S180 sarcoma-bearing Kunming mice from 7 days before to 14 days after tumor inoculation, a host-preconditioning plus continuous-exposure regimen.

RESULTS: RMK reduced tumor growth at both doses (inhibitory rates 40.03% and 48.58%), attenuated thymic atrophy and splenomegaly, and was accompanied by higher proportions of thymic CD4[+]CD8[+] double-positive cells, splenic CD4[+] and CD8[+] T cells and tumor-infiltrating CD8[+] T cells. Tumor-derived suspensions showed mitochondrial depolarization and ROS accumulation, readouts of mitochondrial and redox status that do not identify a cell-death pathway. 16S rRNA sequencing showed higher relative abundances of Lachnospiraceae and Ruminococcaceae, although community structure did not differ significantly. Untargeted metabolomics showed altered bile acid, sphingolipid and steroid-hormone metabolites, with lower aldosterone and cortisol than in tumor-bearing controls. Molecular docking, as an exploratory prediction only, gave the most favorable poses for MHC-I/II (H-2Kb, ΔG = -7.09 kcal/mol) and TCR-proximal kinases (AKT1, ZAP-70, Lck).

CONCLUSIONS: These findings identify RMK as a candidate oral immunomodulatory peptide whose site of action remains to be defined.},
}

Animals
Mice
*Gastrointestinal Microbiome/drug effects
*Sarcoma 180/drug therapy/immunology/metabolism
*T-Lymphocyte Subsets/drug effects/immunology
*Oligopeptides/pharmacology
Thymus Gland/drug effects/pathology

@article {pmid43030274,
year = {2026},
author = {Watrowski, R and Kostov, S and Palumbo, M and Schäfer, SD and Juhasz-Böss, I and Sparić, R and Yordanov, A and Vitale, SG and Alkatout, I},
title = {Berberine and Berberine-Containing Alkaloid Preparations in Preclinical Models of Endometriosis and Adenomyosis: A Systematic Review.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030274},
issn = {2072-6643},
mesh = {*Berberine/pharmacology/therapeutic use ; Female ; *Endometriosis/drug therapy ; *Adenomyosis/drug therapy ; Animals ; Humans ; Disease Models, Animal ; *Alkaloids/pharmacology ; },
abstract = {Background/Objectives: Berberine is increasingly promoted through social media and endometriosis-related websites as a non-hormonal supplement, although its disease-specific evidence remains unclear. This PRISMA-compliant systematic review evaluated experimental and clinical evidence for berberine in endometriosis and adenomyosis. Methods: PubMed/MEDLINE, EBSCOhost, BASE, CNKI Overseas, CENTRAL, and Google Scholar were searched from inception to 3 August 2026, supplemented by targeted manual searches. Clinical studies and experimental studies using endometriosis- or adenomyosis-related cellular or animal models were eligible. Purified berberine formed the primary evidence set. Chemically characterized multi-alkaloid preparations containing berberine were analyzed separately. Risk of bias was assessed with SYRCLE for animal studies and a predefined domain-based appraisal for in vitro studies. A structured qualitative assessment examined confidence in the synthesized findings. Contextual evidence from outside endometriosis and adenomyosis concerning steroid signaling, gut microbiota, microbial metabolites, and GLP-1 was discussed separately. Results: Six preclinical studies were included: three on endometriosis and three on adenomyosis, comprising four in vitro and two animal studies. Five investigated purified berberine and one a protoberberine-rich multi-alkaloid fraction. No clinical study was identified. Berberine reduced cell proliferation or viability and, where directly assessed, migration and invasion. It also reduced inflammatory and angiogenesis-related signaling, and, in an adenomyosis mouse model, myometrial infiltration and hyperalgesia. Reduced proliferation or viability recurred in all four cellular studies, with lower IL-6 and VEGF reported across cellular and animal adenomyosis models. Reported molecular effects involved NF-κB, STAT3, TLR4-associated signaling, VEGF, MMPs, TRPV1, COX-2, miR-429, and lncRNA H19. Gut microbiota modulation, short-chain fatty acids, intestinal barrier function, estrogen metabolism, GPER1, and GLP-1/GLP1R signaling remain plausible indirect routes that have not been demonstrated in disease-specific berberine studies. Conclusions: Berberine shows disease-relevant activity across a small and heterogeneous preclinical evidence base. Clinical efficacy, clinically achievable exposure, reproductive safety, and microbiota- or hormone-mediated effects remain unestablished.},
}

*Berberine/pharmacology/therapeutic use
Female
*Endometriosis/drug therapy
*Adenomyosis/drug therapy
Animals
Humans
Disease Models, Animal
*Alkaloids/pharmacology

@article {pmid43030294,
year = {2026},
author = {Sundoro, UA and Wang, J and Luo, J and Ng, A and Zhou, W and Tan, HE},
title = {Dietary Capsaicin Protects Against Obesity via a Microbiome-Dependent Mechanism Independent of Host TRPV1 Signalling.},
journal = {Nutrients},
volume = {18},
number = {21},
pages = {},
pmid = {43030294},
issn = {2072-6643},
support = {202509060012//China Scholarship Council/ ; NRFF16-2024-0004//National Research Foundation/ ; 32314//Brain & Behavior Research Foundation/ ; MOH-000673-01//National Medical Research Council/ ; PPF-024552, SUG//Nanyang Technological University/ ; //Ministry of Education/ ; },
mesh = {Animals ; *Capsaicin/pharmacology/administration & dosage ; *Obesity/prevention & control/microbiology/metabolism ; *TRPV Cation Channels/metabolism/genetics ; Mice, Knockout ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; Signal Transduction/drug effects ; Male ; Mice, Inbred C57BL ; },
abstract = {Background/Objectives: Dietary compounds simultaneously act on host tissue and gut microbiota, complicating efforts to distinguish direct host-receptor mechanisms from microbiome-mediated effects. Using a common food ingredient as proof-of-principle, this study aims to disentangle capsaicin host receptor signalling from capsaicin-microbiome interactions to determine the role of the gut microbiome in capsaicin-mediated metabolic protection. Methods: We employed a high-fat diet (HFD)-induced obesity model with or without capsaicin supplementation in TRPV1 knockout mice to determine the role of the host receptor. We also depleted the gut microbiota with antibiotics to determine the role of the microbiome. Host metabolic phenotypes were monitored, and microbiome 16S rRNA sequencing and metabolomics were analysed and extended with functional prediction and machine learning algorithms, followed by functional validation in vivo. Results: Capsaicin supplementation significantly protected against HFD-induced obesity, even capsaicin receptor knockout hosts. Crucially, depletion of the microbiota abolished this metabolic protection, demonstrating the microbiome's obligatory role. While capsaicin supplementation did not alter hosts' cumulative food intake, dietary preferences, or energy expenditure, it induced significant shifts in gut microbial diversity and function and triggered extensive faecal metabolomic remodelling which indicate altered nutrient processing including dampened lipid absorption. Consistent with this finding, in vivo functional validation also reveals attenuated circulating lipid response following oral fat administration, and this effect of capsaicin is abrogated without the microbiome. Conclusions: Although capsaicin is well-recognised as a modulator of host appetite and metabolism via canonical host receptor signalling, our strategic use of a host knockout has enabled us to unmask a nuanced microbiome-modulatory role of this chilli pepper ingredient: capsaicin tweaks the microbiome to potentially dial down host fat absorption and protect against high-fat diet-induced obesity. We also highlight a generalisable host knockout experimental framework for distinguishing microbiome-mediated pathways versus direct host receptor mechanisms.},
}

Animals
*Capsaicin/pharmacology/administration & dosage
*Obesity/prevention & control/microbiology/metabolism
*TRPV Cation Channels/metabolism/genetics
Mice, Knockout
Diet, High-Fat/adverse effects
*Gastrointestinal Microbiome/drug effects
Mice
Signal Transduction/drug effects
Male
Mice, Inbred C57BL