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Bibliography on: Fecal Transplantation

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 23 Mar 2025 at 01:42 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: ( "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-03-20
CmpDate: 2025-03-18

Xiao P, Li Y, Li X, et al (2025)

Long-term safety of fecal microbiota transplantation in Chinese children from 2013 to 2023: a single-center retrospective study.

BMC microbiology, 25(1):152.

BACKGROUND: The gut microbiome plays a vital role in influencing various health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a rapid, safe, and effective method for modifying the microbiome. However, there is a lack of long-term safety data regarding FMT in children. This study presents the largest single-center analysis of the long-term safety outcomes of FMT in pediatric patients in China, featuring a substantial sample size and an extended follow-up period to thoroughly examine its safety in children.

METHODS: A retrospective study was conducted on 813 patients who underwent FMT treatments at our hospital from December 2013 to December 2023. All FMT procedures adhered to standardized protocols. The safety of these treatments was retrospectively assessed, focusing on adverse events (AEs) and serious adverse events (SAEs). AEs associated with FMT were categorized as short-term (within 48 h post-FMT) and long-term (within 3 months). Various potential influencing factors for AEs, including sex, age, route of administration, disease type, and consanguineous donor, were examined as independent variables. Significant independent factors and their associated risk ratios with 95% confidence intervals (CI) were determined through multivariate logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.

RESULTS: A total of 813 patients underwent FMT, with a median age of 93 months (range 4-215) and 68.0% being males. The average follow-up time was 32.3 months (range 1-122). All short-term AEs resolved within 48 h, with an overall occurrence rate of 5.8% (47/813). The most common short-term AEs included vomiting (2.0%), abdominal pain (1.6%), diarrhea (0.9%), fever (0.7%), dysphoria (0.4%), and nausea (0.4%). Multivariable analysis revealed that patients with inflammatory bowel disease (IBD) (OR: 3.98, 95% CI: 1.78-8.92, P = 0.001) and those who received FMT via capsules (OR: 0.09, 95% CI: 0.03-0.27, P = 0.000) were independent risk factors for FMT-related AEs. All 813 patients were followed up for at least 1 month, with 78.8% followed for more than 12 months. No long-term AEs occurred during the longest follow-up period of 122 months.

CONCLUSIONS: FMT is a promising treatment option that appears to be safe and well tolerated. This study stands out for its substantial sample size, making it's the largest reported series in pediatrics, as well as for having the longest follow-up period for FMT in this population.

CLINICAL TRIAL NUMBER: Not applicable.

RevDate: 2025-03-20

Oami T, Shimazui T, Yumoto T, et al (2025)

Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets.

Journal of intensive care, 13(1):16.

BACKGROUND: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

MAIN BODY: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

CONCLUSION: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.

RevDate: 2025-03-20

Li L, Li T, Liang X, et al (2025)

A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.

Cell discovery, 11(1):25.

According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.

RevDate: 2025-03-20
CmpDate: 2025-03-17

Dongre DS, Saha UB, SD Saroj (2025)

Exploring the role of gut microbiota in antibiotic resistance and prevention.

Annals of medicine, 57(1):2478317.

BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.

RevDate: 2025-03-17
CmpDate: 2025-03-17

Newsome RC, McGriff C, Gharaibeh RZ, et al (2025)

Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice.

Journal of visualized experiments : JoVE.

Germ-free mice are an important investigation tool for understanding the contribution of microorganisms in host health and disease, enabling assessment of the specific role of individuals, defined or complex groups of microorganisms in host response. Traditionally bred and reared in flexible-film or semi-rigid isolators, germ-free mouse husbandry and experimental manipulation are costly and require numerous trained staff and a large space footprint in animal housing facilities. The IsoPositive caging system allows for experimental manipulation of germ-free mice in individual, hermetically-sealed, positive-pressure isolator cages (isocages), reducing cost and enabling greater flexibility in experimental manipulations. Here, a protocol is described for transferring germ-free mice from breeding isolators to isocages and subsequent fecal transfer from human donor stool into mice to create stable long-term gut "humanized" mice for future studies. The materials and preparation needed for the utilization of the isocage system are described, including the use of chlorine-dioxide sterilant chemical sterilant to clean cages, supplies, equipment, and personal protective equipment. The methods for confirming the germ-free status of transferred mice and how to determine contamination in the caging system are discussed. The procedure for husbandry, including bedding, food, and water supply, is further discussed. The protocol for human fecal slurry preparation and gavage into germ-free mice to create gut "humanized" mice, along with stool collection to monitor the microbial community composition of these mice, are described. An experiment illustrates that two weeks post-human fecal transplant allows for stable colonization of donor microbiota in the murine hosts, enabling subsequent experimental usage. Furthermore, the collection of humanized mouse feces in viability preservation media, enabling use in further functional experiments, is described. Overall, these methods allow for the safe and effective establishment of humanized mouse communities in experimental gnotobiotic cages for further manipulation.

RevDate: 2025-03-18

Wang X, Wang WY, Yu XL, et al (2025)

Comprehensive review of Clostridium difficile infection: Epidemiology, diagnosis, prevention, and treatment.

World journal of gastrointestinal pharmacology and therapeutics, 16(1):100560.

In recent years, nosocomial infections caused by Clostridium difficile (C. difficile) have risen, becoming a leading cause of hospital-acquired diarrhea. The global prevalence of C. difficile infection (CDI) varies across regions and populations. The diagnosis relies primarily on laboratory testing, including toxin, glutamate dehydrogenase, and nucleic acid amplification tests. Treatment strategies for CDI include antimicrobial therapy (e.g., metronidazole, vancomycin, and fidamycin), fecal transplantation, and immunotherapy (e.g., belotozumab), depending on the patient's specificity and severity. This paper reviews recent research on CDI's epidemiological characteristics, risk factors, diagnosis, treatment, and prevention, aiming to support hospitals and public health initiatives in implementing effective detection, prevention, and treatment strategies.

RevDate: 2025-03-17

Le PH, Chen CL, Kuo CJ, et al (2025)

Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.

RevDate: 2025-03-19
CmpDate: 2025-03-17

Liu Y, Liu J, Ren R, et al (2025)

Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m[6]A in white adipose tissue by gut microbiota.

Microbiome, 13(1):75.

BACKGROUND: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

RESULTS: Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m[6]A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m[6]A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m[6]A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m[6]A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.

CONCLUSIONS: Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m[6]A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.

RevDate: 2025-03-15

Fan J, Wu Y, Wang X, et al (2025)

The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis.

Journal of advanced research pii:S2090-1232(25)00177-8 [Epub ahead of print].

INTRODUCTION: The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

OBJECTIVES: This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

METHODS: Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

RESULTS: GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

CONCLUSIONS: L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.

RevDate: 2025-03-16

Hajjeh O, Rajab I, Bdair M, et al (2025)

Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease.

Neuroscience, 572:232-247 pii:S0306-4522(25)00216-7 [Epub ahead of print].

The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.

RevDate: 2025-03-15
CmpDate: 2025-03-15

Lin D, Howard A, Raihane AS, et al (2025)

Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes.

Current neurology and neuroscience reports, 25(1):23.

PURPOSE OF REVIEW: A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

RECENT FINDINGS: The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

RevDate: 2025-03-18

Oliwa-Libumska K, Jaworska-Czerwinska A, Mallek-Grabowska M, et al (2025)

Fecal microbiota transplantation in a patient hospitalized in the intensive care unit - Case report.

Heliyon, 11(4):e42793.

Clostridioides difficile infections are difficult and serious problem occurring in patients staying in intensive care units. In recent years, the number and severity of these infections, as well as the mortality rate, have been increasing, posing a serious epidemiological problem. This is caused, among other factors, by stressors, artificial nutrition, and sepsis, which lead to disturbances in the patients' microbiome. Basic method of treatment is antibiotic therapy, however some patients experience recurrences of the infection. Fecal Microbiota Transplantation (FMT) is one of the alternative methods used in treating recurring infections of Clostridioides difficile etiology (Clostridioides Difficile Infection, CDI). The presented case refers to a patient with severe pseudomembranous enterocolitis who underwent FMT twice. This report highlights the role of FMT in the treatment of severe Clostridioides difficile infections in critically ill patients.

RevDate: 2025-03-14

Frontiers Production Office (2025)

Erratum: Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.

Frontiers in microbiology, 16:1576969.

[This corrects the article DOI: 10.3389/fmicb.2025.1452423.].

RevDate: 2025-03-14
CmpDate: 2025-03-14

Özdirik B, Berger H, Tonetti FR, et al (2025)

Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis.

Liver international : official journal of the International Association for the Study of the Liver, 45(4):e16181.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut-liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.

METHODS: To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.

RESULTS: High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels.

CONCLUSION: Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.

RevDate: 2025-03-18
CmpDate: 2025-03-14

Jahn B, Bundo M, Arvandi M, et al (2025)

One in three adenomas could be missed by white-light colonoscopy - findings from a systematic review and meta-analysis.

BMC gastroenterology, 25(1):170.

BACKGROUND: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice.

METHODS: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity.

RESULTS: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5 mm; 27%, adenomas 6-9 mm; 12%, adenomas ≥ 10 mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%).

CONCLUSIONS: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".

RevDate: 2025-03-14
CmpDate: 2025-03-14

Manns MP, Bergquist A, Karlsen TH, et al (2025)

Primary sclerosing cholangitis.

Nature reviews. Disease primers, 11(1):17.

Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.

RevDate: 2025-03-13

Yang S, Pan H, Wang T, et al (2025)

Bacillus paralicheniformis-mediated gut microbiota promotes M2 macrophage polarization by inhibiting P38 MAPK signaling to alleviate necrotizing enterocolitis and apoptosis in mice.

Microbiological research, 296:128136 pii:S0944-5013(25)00092-8 [Epub ahead of print].

Clostridial necrotizing enterocolitis is a severe gastrointestinal disease induced by Clostridium, strongly associated with intestinal dysbiosis. Fecal microbiota transplantation (FMT) has proven effective in treating gastrointestinal diseases by remodeling intestinal microbial homeostasis. However, it remains unclear whether FMT from donors with beneficial microbiota can improve the recipient's intestinal function more efficiently. This study found that probiotic Bacillus paralicheniformis SN-6-mediated gut microbiota effectively prevent Clostridial necrotizing enteritis and explored the underlying molecular mechanisms. Data demonstrated that SN-6 altered gut microbiota composition, ameliorated Clostridium perfringens-induced intestinal microbiota dysbiosis and metabolic reprogramming, particularly enhancing tryptophan metabolism. This led to a marked reduction in intestinal barrier damage and inflammation. FMT from SN-6-treated mice reduced jejunal inflammation in Clostridium perfringens-infected mice, strengthened jejunal barrier and enriched beneficial bacteria, such as Lactobacillus, Blautia, Akkermansia. Furthermore, 3-indoleacetic acid (IAA), a metabolite enriched by SN-6, activated aryl hydrocarbon receptor (AhR), suppressed the P38 mitogen-activated protein kinase (P38 MAPK) signaling, and drove macrophage polarization from M0 to M2-type, thereby reducing apoptosis and excessive inflammation. This study highlights Bacillus paralicheniformis SN-6 as a key modulator of intestinal immunomodulation via the gut microbiota-IAA-AhR-P38 MAPK axis, offering a potential therapeutic target for preventing and controlling clostridial necrotizing enteritis.

RevDate: 2025-03-13

Menozzi E, Schapira AHV, P Borghammer (2025)

The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.

Movement disorders clinical practice [Epub ahead of print].

BACKGROUND: The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.

AIMS: We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.

METHODS: We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.

RESULTS: Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological α-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological α-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.

CONCLUSION: Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.

RevDate: 2025-03-14

Ullah H, Arbab S, Chang C, et al (2025)

Gut microbiota therapy in gastrointestinal diseases.

Frontiers in cell and developmental biology, 13:1514636.

The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.

RevDate: 2025-03-13

Ma Z, Wen X, Zhang Y, et al (2025)

Thymol Alleviates Colitis by Modulating Intestinal Barrier Damage, Gut Microbiota, and Amino Acid Metabolic Pathways.

Journal of agricultural and food chemistry [Epub ahead of print].

Thymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.

RevDate: 2025-03-15
CmpDate: 2025-03-13

Gao Y, Borjihan Q, Zhang W, et al (2025)

Complex Probiotics Ameliorate Fecal Microbiota Transplantation-Induced IBS in Mice via Gut Microbiota and Metabolite Modulation.

Nutrients, 17(5):.

Background/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Emerging evidence implicates gut microbiota dysbiosis in IBS pathogenesis, and probiotic interventions targeting microbial modulation hold therapeutic promise. Methods: this study used fecal microbiota transplantation to establish a mouse model of IBS before evaluating the effects of the complex probiotic by using metagenomics and targeted metabolomics to explore the potential mechanism. Results: After 14 days, the probiotic relieved constipation, reduced inflammation and intestinal permeability, lowered 5-HT levels and increased serotonin transporter (SERT) expression in tissues. Metagenomic analysis showed a reduced inflammation-related species abundance. It also decreased fecal butyric acid, acetic acid and tryptophan levels in IBS mice. Conclusions: The probiotic complex effectively alleviated IBS symptoms in mice by modulating gut microbiota and fecal metabolites, providing insights for future IBS research and treatment.

RevDate: 2025-03-15
CmpDate: 2025-03-13

Hatamnejad MR, Medzikovic L, Dehghanitafti A, et al (2025)

Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.

International journal of molecular sciences, 26(5):.

The effect of the gut microbiota extends beyond their habitant place from the gastrointestinal tract to distant organs, including the cardiovascular system. Research interest in the relationship between the heart and the gut microbiota has recently been emerging. The gut microbiota secretes metabolites, including Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids (BAs), indole propionic acid (IPA), hydrogen sulfide (H2S), and phenylacetylglutamine (PAGln). In this review, we explore the accumulating evidence on the role of these secreted microbiota metabolites in the pathophysiology of ischemic and non-ischemic heart failure (HF) by summarizing current knowledge from clinical studies and experimental models. Elevated TMAO contributes to non-ischemic HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy and fibrosis, impairments of mitochondrial energy production, DNA methylation pattern change, and intracellular calcium transport. Also, high-level TMAO can promote ischemic HF via inflammation, histone methylation-mediated vascular fibrosis, platelet hyperactivity, and thrombosis, as well as cholesterol accumulation and the activation of MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell myocardial infiltration, and HDAC 5 and 6 activities, leading to non-ischemic HF, while reactive oxygen species production and the hyperactivation of caveolin-ACE axis result in ischemic HF. An altered BAs level worsens contractility, opens mitochondrial permeability transition pores inducing apoptosis, and enhances cholesterol accumulation, eventually exacerbating ischemic and non-ischemic HF. IPA, through the inhibition of nicotinamide N-methyl transferase expression and increased nicotinamide, NAD+/NADH, and SIRT3 levels, can ameliorate non-ischemic HF; meanwhile, H2S by suppressing Nox4 expression and mitochondrial ROS production by stimulating the PI3K/AKT pathway can also protect against non-ischemic HF. Furthermore, PAGln can affect sarcomere shortening ability and myocyte contraction. This emerging field of research opens new avenues for HF therapies by restoring gut microbiota through dietary interventions, prebiotics, probiotics, or fecal microbiota transplantation and as such normalizing circulating levels of TMAO, SCFA, BAs, IPA, H2S, and PAGln.

RevDate: 2025-03-15
CmpDate: 2025-03-13

Wang K, Hu Y, Wu Y, et al (2025)

The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid in Escherichia coli-Induced Colitis.

International journal of molecular sciences, 26(5):.

Pathogenic Escherichia coli (E. coli) is a widely distributed pathogen that can cause varying degrees of zoonotic diseases, and infected animals often experience intestinal inflammation accompanied by diarrhea and dysbiosis. Previously, for the first time, we isolated Escherichia coli primarily of type B2 from a large-scale dairy farm in Yunnan, China. The 16s rRNA sequencing showed significant differences in the gut microbiota of calves infected with B2 E. coli, with higher abundance of harmful bacteria and lower abundance of beneficial bacteria compared with healthy calves. The metabolomics indicated that the concentrations of oxoadipic acid, 16-oxopalmitate, oerillyl alcohol, palmitoleic acid, and 4-phenylbutyrate (4-PBA) were significantly higher in the healthy group than in the infected group. The mouse model was established to assess the regulatory effect of 4-PBA on E. coli-induced colitis. Both oral administration of 4-PBA and fecal microbiota transplantation (FMT) had strong resistance to E. coli infection, improved survival rate and body weight, reduced intestinal tissue damage, decreased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and restrained TLR4/MyD88/NF-κB pathway. Our study demonstrated that 4-PBA could relieve E. coli-induced colitis by improving gut microbiota structure and inhibiting the expression of pro-inflammatory cytokines through the TLR4/MyD88/NF-κB pathway. The present finding reveals the therapeutic potential of the gut-microbiota-derived metabolite 4-PBA for the treatment of colitis caused by E. coli.

RevDate: 2025-03-17
CmpDate: 2025-03-17

Durkee-Shock J, Cohen A, Maghzian N, et al (2025)

Reconstitution of Norovirus-Specific T-Cell Responses Following Hematopoietic Stem Cell Transplantation in Patients With Inborn Errors of Immunity and Chronic Norovirus Infection.

The Journal of infectious diseases, 231(3):773-783.

BACKGROUND: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.

METHODS: Two patients with inborn errors of immunity, X-linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T-cell (NST) response, B-cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant (HSCT) setting before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing.

RESULTS: The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in 1 patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-versus-host disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T-cell compartments that recognized multiple norovirus structural and nonstructural viral antigens. T-cell responses were minimal during active CNI but detectable after resolution. Mapping of NST responses between the patient with DOCK8 deficiency and his matched sibling donor were nearly identical. B-cell reconstitution or new endogenous antibody production for immunoglobulin A or immunoglobulin G was not observed.

CONCLUSIONS: This report is the first to demonstrate reconstitution of NST immunity after HSCT closely temporally aligned with clearance of CNI, suggesting that cellular immunity is sufficient for norovirus clearance.

RevDate: 2025-03-15

Luo S, Huang X, Chen S, et al (2025)

The Gut Microbiota of the Greater Horseshoe Bat Confers Rapidly Corresponding Immune Cells in Mice.

Animals : an open access journal from MDPI, 15(5):.

BACKGROUND: Emerging infectious diseases threaten human and animal health, with most pathogens originating from wildlife. Bats are natural hosts for many infectious agents. Previous studies have demonstrated that changes in some specific genes in bats may contribute to resistance to viral infections, but they have mostly overlooked the immune function of the bat gut microbiota.

AIMS: In this study, we used fecal transplants to transfer the gut microbiota from the Greater Horseshoe Bat (Rhinolophus ferrumequinum) into mice treated with antibiotics. The gut microbiota changes in mice were detected using 16S rRNA high-throughput sequencing technology. Flow cytometry was used to detect changes in associated immune cells in the spleen and mesenteric lymph nodes of the mice.

RESULTS: The results showed that the gut microbiota of mice showed characteristics of some bat gut microbiota. The Greater Horseshoe Bat's gut microbiota changed some immune cells' composition in the spleen and mesenteric lymph nodes of mice and also conferred a faster and higher proportion of natural killer cell activation.

CONCLUSION: This result provides new evidence for the regulatory immune function of bat gut microbiota and contributes to a deeper insight into the unique immune system of bats.

RevDate: 2025-03-15
CmpDate: 2025-03-13

Cao H, Xu J, Wang H, et al (2025)

Fecal microbiota transplantation mitigates postdieting weight regain in mice by modulating the gut-liver axis.

BMC microbiology, 25(1):135.

BACKGROUND: Dysbiosis of the microbiome is strongly associated with weight rebound after dieting. However, the interactions between the host and microbiome and their relevance to the pathogenesis of post-diet weight rebound remain unclear.

PURPOSE: This study aimed to evaluate the effects of fecal microbiota transplantation (FMT) on post-diet weight regain and to investigate the underlying mechanisms by which FMT inhibits weight regain.

METHODS: FMT was administered once daily to mice for 5 weeks. Gas chromatography tandem mass spectrometry was employed to analyze short-chain fatty acid levels in serum, ultrahigh-performance liquid chromatography tandem mass spectrometry was utilized for analyzing hepatic lipid metabolites, and shotgun metagenomic sequencing was applied to examine the intestinal microbiome.

RESULTS: FMT reduced weight regain and prevented lipid accumulation in both liver and adipose tissue while also improving glucose intolerance in mice. Furthermore, FMT increased the abundance of Enterorhabdus caecimuris and decreased the abundances of Burkholderiales, Sutterellaceae, Turicimonas muris, Bacteroides stercorirosoris, and Acetivibrio ethanolgignens within the gut microbiota. Additionally, elevated propionic acid levels and significant alterations in hepatic lipid metabolites were observed following FMT administration.

CONCLUSIONS: Our findings demonstrate that FMT effectively mitigates post-diet weight regain and associated complications. These effects are mediated through interactions between the gut microbiota and the liver via the gut-propionic acid-liver axis.

CLINICAL TRIAL NUMBER: Not applicable.

RevDate: 2025-03-13
CmpDate: 2025-03-13

Bakhshandi AK, Minasazi A, Yeganeh O, et al (2025)

Therapeutic potential of microbiota modulation in psoriasis: current evidence and future directions.

Archives of dermatological research, 317(1):561.

The human microbiota plays a significant role in health and the development of autoimmune diseases by maintaining gut-skin homeostasis through diverse microbial communities. Dysbiosis, or imbalance in these communities, is increasingly recognized as a contributing factor in the pathogenesis of autoimmune and inflammatory diseases, including psoriasis. Psoriasis is characterized by immune dysregulation, leading to red and scaly plaques that significantly reduce patients' quality of life. Current evidence highlights the gut microbiota's critical role in driving immune responses and chronic inflammation associated with psoriasis. Therapeutic strategies aimed at restoring microbial balance, such as probiotics, have demonstrated promise in reducing disease severity. Additionally, fecal microbiota transplantation (FMT) has emerged as a novel intervention, with early studies suggesting its potential to alleviate symptoms by correcting gut dysbiosis. These approaches underscore the importance of microbiota-targeted therapies in addressing the systemic nature of psoriasis and pave the way for advancements in personalized treatment strategies.

RevDate: 2025-03-15

Attauabi M, Madsen GR, Bendtsen F, et al (2024)

Multidimensional Patient-Reported Outcomes and Quality of Life at Diagnosis of IBD: A Population-Based Inception Cohort Study.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(24)00963-7 [Epub ahead of print].

BACKGROUND AND AIMS: Patient-reported outcomes (PROs) are pivotal in assessing treatment efficacy and estimating the burden of inflammatory bowel diseases (IBDs). We investigated PROs at the time of IBD diagnosis.

METHODS: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and disease activity-related PROs were assessed in the Copenhagen IBD Inception Cohort, a prospective, population-based cohort of patients newly diagnosed with IBD between May 2021 and May 2023.

RESULTS: A total of 203 ulcerative colitis (UC) and 116 Crohn's disease (CD) patients were recruited. At diagnosis, 160 (78.8%) and 99 (85.3%) patients with UC and CD, respectively, reported moderate-to-severe impairment in at least 1 PRO (P = .18), with 89 (43.8%) and 74 (63.8%), respectively, reporting moderate-to-severe impairment in at least 2 PROs (P < .01). Being female, the disease extent of UC, and extraintestinal manifestations were associated with impaired PROs. There were no differences found according to CD phenotype. FACIT-F, IBD-DI, and SIBDQ scores showed weak, but significant, correlations with the Mayo endoscopic score in UC, and the FACIT-F score with C-reactive protein. In CD, SIBDQ, IBD-DI, and FACIT-F correlated moderately with C-reactive protein and fecal calprotectin but not with the endoscopic severity of CD. None of the PROs correlated with iron, ferritin, or vitamin D levels. Among the most prevalent symptoms reported were fatigue, abdominal pain, urgency, and passing of blood in both CD and UC.

CONCLUSIONS: We found a substantial patient-reported disease burden in newly diagnosed IBD, underscoring the importance of vigilant PRO monitoring in clinical practice.

RevDate: 2025-03-12

Le PH, Yeh YM, Chen YC, et al (2025)

Fecal microbiota transplantation for vancomycin-resistant Clostridium innocuum infection in inflammatory bowel disease: A pilot study evaluating safety and clinical and microbiota outcome.

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi pii:S1684-1182(25)00064-7 [Epub ahead of print].

BACKGROUND: Clostridium innocuum is a vancomycin-resistant pathobiome associated with poor clinical outcomes in inflammatory bowel disease (IBD). In ulcerative colitis (UC), it correlates with reduced remission rates, while in Crohn's disease (CD), it is linked to creeping fat formation and intestinal strictures. Notably, some patients experience refractory or recurrent C. innocuemailum infections despite metronidazole treatment. This study evaluates the safety and efficacy of single-dose fecal microbiota transplantation (FMT) in IBD patients with refractory or recurrent C. innocuum infections.

METHODS: We conducted a feasibility pilot study involving seven IBD patients (3 CD, 4 UC) with refractory (n = 5) or recurrent (n = 2) C. innocuum infections following metronidazole treatment. Patients underwent single-dose FMT and were monitored for six months.

RESULTS: No adverse events were recorded. All participants demonstrated improved disease activity post-FMT, as assessed by the Crohn's Disease Activity Index and Mayo Score. However, a mild increase in symptom severity was noted at six months. Follow-up cultures showed persistent C. innocuum infection in one patient and asymptomatic recurrence in another at three months. Alpha diversity of the gut microbiome increased post-FMT, and Bray-Curtis dissimilarity analysis revealed a microbiota composition more similar to that of the donor.

CONCLUSION: Single-dose FMT appears to be a safe and feasible therapeutic approach for refractory or recurrent C. innocuum infections in IBD patients, with potential benefits in disease activity and microbiome restoration. Further studies are warranted to optimize long-term outcomes.

RevDate: 2025-03-14
CmpDate: 2025-03-12

Habeeb TAAM, Chiaretti M, Kryvoruchko IA, et al (2025)

Mucosal advancement flap versus ligation of the inter-sphincteric fistula tract for management of trans-sphincteric perianal fistulas in the elderly: a retrospective study.

International journal of colorectal disease, 40(1):61.

PURPOSE: There is no consensus on the standard approach for trans-sphincteric perianal fistulas (TPAF) in the elderly population. The most commonly used sphincter-saving procedures are ligation of the inter-sphincteric fistula tract (LIFT) and mucosal advancement flap (MAF). We aimed to evaluate the incidence and risk factors for recurrence and incontinence in elderly patients with TPAF using both approaches.

METHODS: This retrospective study included 257 patients who underwent LIFT (136 patients) or MAF (121 patients) for de novo and cryptoglandular TPAF between July 2018 and July 2021. Recurrent fistulas were clinically and radiologically detected using MRI. Postoperative incontinence was evaluated using the Wexner score and anorectal manometry. Logistic regression analysis was used to detect the risks of recurrence and incontinence.

RESULTS: The median ages of the patients were 68 (64, 74) and 68 (65, 74) years in the LIFT and MAF groups, respectively. Higher recurrence rates were observed after LIFT (17 (12.5%)) than after MAF (13 (10.7%)), but the difference was not statistically significant (P = 0.662). Postoperative incontinence was observed in 18 patients (13.2%) and seven patients (5.8%) in the LIFT and MAF groups, respectively (P = 0.044). The predictors for fistula recurrence were smoking (OR, 75.52; 95% CI, 1.02 to 5611.35; P = 0.049), length of tract (OR, 17.3; 95% CI, 1.49 to 201.13; P = 0.023), and CD classification (OR, 7.08; 95% CI, 1.51 to 33.14; P = 0.013). A low Charlson comorbidity index score (≤ 5) (OR, 0.68; 95% CI, 0.47 to 0.99; P = 0.046) and high postoperative mean squeeze anal pressure (OR, 0.97; 95% CI, 0.95 to 0.99; P = 0.001) were significant factors associated with reduced risk of incontinence. In particular, LIFT was associated with a significantly higher risk of incontinence than MAF (OR, 2.089; 95% CI, 1.006 to 4.33; P = 0.04).

CONCLUSIONS: The healing rates of MAF and LIFT procedures did not differ significantly; however, continence was significantly better after MAF. MAF should be added to the guidelines as a good option for the treatment of TPAF in elderly patients.

TRIAL REGISTRATION: The study was registered as a clinical trial www.

CLINICALTRIALS: gov (NCT06616662).

RevDate: 2025-03-12

Chen M, Song Y, Pan J, et al (2025)

Effects of faecal microbiota transplantation supplemented with inulin on early immunity and immune organ histomorphology in chickens.

British poultry science [Epub ahead of print].

1. Faecal microbiota transplantation (FMT) is a technique that promotes gut microbiota diversity and abundance by transplantation of faeces into a recipient's gastrointestinal tract via multiple routes.2. Inulin, a plant polysaccharide, is a natural functional dietary fibre found in a variety of plants, including vegetables and fruits. Inulin can inhibit pathogenic bacterial growth by lowering pH, promote mineral absorption and improve intestinal barrier integrity.3. In this study 90 one-day-old chicks were randomly into three groups; control (CON) group was fed a basic diet; FMT group fed two diets containing 40 ml faecal microbial suspension; and INU group fed a diet containing 1.5% inulin and 40 ml faecal microbial suspension.4. Administering the FMT mixed with inulin effectively reduced blood levels of IL-1β, IL-4 and IL-6, promoted the growth of thymus, bursa of Fabricius and spleen. In addition, it enhanced intestinal barrier function, increased intestinal goblet cells and Paneth cells production, promoted probiotic colonisation and butyrate formation and reduced intestinal inflammation.5. In summary, inulin mixed with FMT promoted the growth of the bursa of Fabricius, thymus and spleen as well as facilitated early growth of chick by promoting intestinal health, reducing inflammation and boosting chick immunity.

RevDate: 2025-03-14
CmpDate: 2025-03-12

Świdnicka-Siergiejko A, Daniluk J, Miniewska K, et al (2025)

Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition.

Cells, 14(5):.

An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.

RevDate: 2025-03-12
CmpDate: 2025-03-12

Organski AC, Rajwa B, Reddivari A, et al (2025)

Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.

Gut microbes, 17(1):2476562.

The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.

RevDate: 2025-03-13
CmpDate: 2025-03-12

Ren S, Zhang Y, Wang X, et al (2025)

Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.

Frontiers in immunology, 16:1526967.

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.

RevDate: 2025-03-11

Huang H, Zhao T, W Ma (2025)

Omega-3 polyunsaturated fatty acids attenuates cognitive impairment via the gut-brain axis in diabetes-associated cognitive dysfunction rats.

Brain, behavior, and immunity pii:S0889-1591(25)00083-2 [Epub ahead of print].

Diabetes-related cognitive dysfunction (DACD) is a comorbidity of type 2 diabetes that has a negative effect on patients' quality of life. Research has indicated that disruption of the gut microbiota (GM) may be linked to dementia with altered cognitive performance. Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFAs) may reverse DACD. The present study aimed to assess the effects of an n-3 PUFA intervention and fecal microbiota transplantation (FMT) on high-fat and streptozotocin-induced DACD model rats. In DACD rats, n-3 PUFA treatment restored fasting blood glucose (FBG) levels and cognitive function, increased the expression of anti-inflammatory cytokines and downregulated the expression of proinflammatory cytokines in the cortex and colon. Additionally, the expression of the postsynaptic density protein-95 mRNA and protein varied with n-3 PUFA treatment. Treatment with n-3 PUFAs also increased the expression of tight junction proteins. Beneficial and short-chain fatty acid-producing bacteria were more abundant when rats were exposed to n-3 PUFAs. After FMT from the rats with DACD symptoms that were improved by the n-3 PUFA dietary intervention into another batch of DACD rats, we observed recovery in recipient DACD rats. These results indicated that the alleviation of DACD symptoms by n-3 PUFAs was attributed to gut microbiota remodeling.

RevDate: 2025-03-12
CmpDate: 2025-03-11

Ganesan R, Thirumurugan D, Vinayagam S, et al (2025)

A critical review of microbiome-derived metabolic functions and translational research in liver diseases.

Frontiers in cellular and infection microbiology, 15:1488874.

Significant changes in gut microbial composition are associated with chronic liver disease. Using preclinical models, it has been demonstrated that ethanol/alcohol-induced liver disease is transmissible through fecal microbiota transplantation (FMT). So, the survival rate of people with severe alcoholic hepatitis got better, which suggests that changes in the makeup and function of gut microbiota play a role in metabolic liver disease. The leaky intestinal barrier plays a major role in influencing metabolic-related liver disease development through the gut microbiota. As a result, viable bacteria and microbial products can be transported to the liver, causing inflammation, contributing to hepatocyte death, and causing the fibrotic response. As metabolic-related liver disease starts and gets worse, gut dysbiosis is linked to changes in the immune system, the bile acid composition, and the metabolic function of the microbiota in the gut. Metabolic-related liver disease, as well as its self-perpetuation, will be demonstrated using data from preclinical and human studies. Further, we summarize how untargeted treatment approaches affect the gut microbiota in metabolic-related liver disease, including dietary changes, probiotics, antibiotics, and FMT. It discusses how targeted therapies can improve liver disease in various areas. These approaches may improve metabolic-related liver disease treatment options.

RevDate: 2025-03-13
CmpDate: 2025-03-11

Madill-Thomsen KS, Venner JM, Parsons DE, et al (2025)

Relating the molecular phenotype of ulcerative colitis to the clinical course.

Scientific reports, 15(1):8342.

The expanding portfolio of targeted therapies for ulcerative colitis (UC) suggests that a more precise approach to defining disease activity will aid clinical decision-making. This prospective study used genome-wide microarrays to characterize gene expression in biopsies from the most inflamed colon segments from patients with UC and analyzed associations between molecular changes and short-term outcomes while on standard-of-care treatment. We analyzed 141 biopsies-128 biopsies from 112 UC patients and 13 biopsies from eight inflammatory bowel disease unclassified (IBDU) patients. Endoscopic disease was associated with expression of innate immunity transcripts, e.g. complement factor B (CFB); inflammasome genes (ZBP1 and PIM2); calprotectin (S100A8 and S100A9); and inflammation-, injury-, and innate immunity-associated pathway analysis terms. A cross-validated molecular machine learning classifier trained on the endoscopic Mayo subscore predicted the endoscopic Mayo subscore with area-under-the-curve of 0.85. A molecular calprotectin transcript score showed strong associations with fecal calprotectin and the endoscopic Mayo subscore. Logistic regression models showed that molecular features (e.g. molecular classifier and molecular calprotectin scores) improved the prediction of disease progression over conventional, clinical features alone (e.g. total Mayo score, fecal calprotectin, physician global assessment). The molecular features of UC showed strong correlations with disease activity and permitted development of machine-learning predictive disease classifiers that can be applied to expanded testing in diverse cohorts.

RevDate: 2025-03-10

Serbanescu M, Lee S, Li F, et al (2025)

Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.

Anesthesia and analgesia pii:00000539-990000000-01218 [Epub ahead of print].

BACKGROUND: Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.

METHODS: We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.

RESULTS: We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus, Roseburia, and Ruminococcus), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).

CONCLUSIONS: These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.

RevDate: 2025-03-13
CmpDate: 2025-03-10

Moutsoglou D, Ramakrishnan P, BP Vaughn (2025)

Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights.

Gut microbes, 17(1):2477255.

Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.

RevDate: 2025-03-11

Borah P, Gautam V, Kumar V, et al (2025)

Fecal Microbiota Transplantation for Refractory Clostridioides difficile Infection Post Haploidentical Transplant for Pediatric Acute Myeloid Leukemia.

Blood cell therapy, 8(1):170-172.

BACKGROUND: Clostridioides difficile (C. difficile) infections are common in immunosuppressed patients. Sometimes these are difficult to treat in post-bone marrow transplant situations.

METHODS: A 2-year-old child with relapsed acute myeloid leukemia underwent a haploidentical bone marrow transplant. He developed 30-40 episodes/day of loose watery stools on day +19. The stool was positive for C. difficile infection. He failed oral vancomycin and metronidazole therapy. He received a fecal microbiota transplant (FMT) on day +43. The donor was the same sister who donated hematopoietic stem cells.

RESULTS: Three days later (day +46), stool frequency reduced from 22-24/day to 12-14/day. Color normalized to yellow and consistency improved from watery to semisolid without blood. He was discharged from the hospital 10 days after FMT on oral vancomycin and nasogastric feeding. Stool tested for C. difficile 16 days after FMT was negative and oral vancomycin was stopped.

CONCLUSION: Fecal microbiota transplant could be a useful modality in children with severe C. difficile infection post-bone marrow transplant.

RevDate: 2025-03-11

Yi D, Li T, Xiao Y, et al (2025)

Fecal microbiota transplantation for the treatment of intestinal and extra-intestinal diseases: Mechanism basis, clinical application, and potential prospect.

Bioengineering & translational medicine, 10(2):e10728.

To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.

RevDate: 2025-03-10

Kim M, Wang J, Pilley SE, et al (2025)

Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.

bioRxiv : the preprint server for biology pii:2024.05.03.592475.

Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g . osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.

RevDate: 2025-03-09

Zhang W, Yi C, Song Z, et al (2025)

Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 140:156560 pii:S0944-7113(25)00200-4 [Epub ahead of print].

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive decline, which can result in diabetic cognitive impairment (DCI). Recent studies have indicated that gut microbiota plays a significant role in the development of DCI. Tangliping Decoction (TLP), a traditional Chinese medicine compound, contains various active ingredients that have been shown to regulate the microecology of gut microbiota and potentially improve DCI. However, it remains unclear whether TLP can improve DCI by modulating gut microbiota, as well as which specific component is primarily responsible for these effects.

PURPOSE: Assess the impact of TLP on alleviating DCI and investigate the contribution of quercetin (QR), the core blood-absorbed component of TLP, in this process. and investigate the underlying mechanisms through which TLP and QR enhance DCI by modulating gut microbiota composition.

STUDY DESIGN AND METHODS: Initially, experiments such as morris water maze (MWM), morphological analysis, and 16S ribosomal RNA (16S rRNA) gene amplicon sequencing from DCI mice, were performed to validate the pharmacological efficacy of TLP in mitigating DCI. The results indicated that TLP possesses the capacity to modulate the composition and quantity of gut microbiota and safeguard the integrity of the gut barrier and brain barrier. Secondly, high performance liquid chromatography coupled with high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with network pharmacology methods were used to screen for blood-absorbed components, suggesting that QR may be a potential core blood-absorbed component of TLP in the treatment of DCI. Subsequently, the pharmacological efficacy of QR in ameliorating DCI was confirmed, and the characteristics of gut microbiota as well as the permeability of the gut and brain barrier, were assessed. Finally, fecal microbiota transplantation (FMT) experiments were conducted, wherein fecal matter from TLP and QR-treated mice (donor mice) was transplanted into pseudo-sterile DCI mice with antibiotic-induced depletion of gut microbiota. This approach aimed to elucidate the specific mechanisms by which TLP and QR improve DCI through the modulation of the structure, composition, and abundance of gut microbiota.

RESULTS: TLP and QR have the potential to enhance learning and memory capabilities in DCI mice, as well as reduce homeostasis model assessment insulin resistance (HOMA-IR) and restore homeostasis model assessment-β function (HOMA- β), leading to increased fasting insulin (FIN) levels and decreased fasting blood glucose (FBG) levels. Simultaneously, the administration of FMT from donor mice to pseudo-sterile DCI mice has been shown to alter the composition and abundance of gut microbiota, leading to amelioration of pathological damage in the colon and hippocampal tissues. Ultimately, FMT utilizing fecal suspensions from donor mice treated with TLP and QR improved cognitive function in pseudo-sterile DCI mice, restore gut microbiota dysbiosis, and maintained the integrity of the gut and brain barriers.

CONCLUSION: The results of this study indicate that TLP and its core component, QR, which is absorbed into the bloodstream, improve DCI through a gut microbiota-dependent mechanism, providing further evidence for gut microbiota as a therapeutic target for DCI treatment.

RevDate: 2025-03-09

Tang X, Huang L, Ma W, et al (2025)

Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 140:156580 pii:S0944-7113(25)00220-X [Epub ahead of print].

BACKGROUND: traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.

PURPOSE: to investigate the effect of gut microbiota and metabolites disorder on TBI injury.

STUDY DESIGN: 16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.

METHODS: fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.

RESULT: rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.

CONCLUSION: our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.

RevDate: 2025-03-09

Mu X, Feng L, Wang Q, et al (2025)

Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis.

Redox biology, 81:103580 pii:S2213-2317(25)00093-X [Epub ahead of print].

Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.

RevDate: 2025-03-07
CmpDate: 2025-03-08

Alexandra P, Noémie P, Solène SB, et al (2025)

Evaluation of pelvic floor rehabilitation in the prevention of low anterior resection syndrome: Study protocol of the CONTICARE trial.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, 27(3):e70045.

AIM: Bowel dysfunction following sphincter-preserving rectal resection for cancer, commonly referred to as low anterior resection syndrome (LARS), significantly impacts patients' quality of life. Preventing this condition is essential for healthcare teams. Postoperative pelvic floor rehabilitation, including anal biofeedback therapy, has shown potential in alleviating established LARS symptoms. This trial aims to evaluate the effectiveness of pelvic floor rehabilitation prior to bowel continuity restoration in preventing LARS in patients undergoing sphincter-preserving rectal resection for cancer.

METHODS: CONTICARE is a national multicentre randomized trial. Patients who have undergone total mesorectal excision with sphincter preservation and a defunctioning stoma (n = 174; 87 per arm) will be randomly assigned to either the rehabilitation or control group before stoma closure. The rehabilitation group will receive systematic pelvic floor rehabilitation, comprising four sessions before and six sessions after stoma closure, following a standardized approach. The control group will receive standard follow-up care, which includes symptom-based therapy after ileostomy closure. The primary outcome measure will be the severity of LARS, assessed using the dedicated LARS score at 6 months. Comparisons of faecal incontinence symptoms, quality of life and complications related to biofeedback therapy will also be evaluated at 6 weeks, 6 months and 1 year between the two groups.

CONCLUSION: Pelvic floor rehabilitation has the potential to enhance symptom management and quality of life for patients following rectal resection by preventing LARS. The combination of anal exercises and biofeedback therapy, which has been extensively studied without reported adverse effects, suggests that the anticipated benefits outweigh any potential risks.

CLINICAL TRIAL REGISTRATION: Registration number NCT03876561, first published on 15 March 2019.

CLINICALTRIALS: gov.

RevDate: 2025-03-11

Luan WW, Gu HW, Qiu D, et al (2025)

Repeated administration of esketamine ameliorates mechanical allodynia in mice with chemotherapy-induced peripheral neuropathy: A role of gut microbiota and metabolites.

Neurochemistry international, 185:105961 pii:S0197-0186(25)00034-8 [Epub ahead of print].

Chemotherapy-induced peripheral neuropathy (CIPN) severely diminishes the quality of life for cancer survivors, yet effective treatments remain scarce. Esketamine, a commonly used anesthetic, has demonstrated neuroprotective effects by restoring gut microbiome dysbiosis. In this study, we investigated the impact of esketamine on nociceptive sensitivity in a mouse model of CIPN and explored the potential involvement of the gut microbiome. In mice treated with oxaliplatin, repeated esketamine doses (in contrast to a single dose) significantly improved the paw withdrawal threshold (PWT). Western blot and qPCR analyses further revealed that repeated esketamine administration markedly reduced microglial activation and neuroinflammation in the dorsal root ganglion (DRG), underscoring its potent anti-inflammatory properties. Moreover, fecal 16S rRNA analysis indicated that esketamine partially restored the abnormal gut microbiota composition (β-diversity). Plasma metabolome analysis showed that repeated esketamine treatment significantly lowered the elevated levels of 6H-indolo[2,3-b]quinoline and restored the reduced levels of (3-exo)-3-[3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octane observed in oxaliplatin-treated mice. In addition, fecal microbiota transplantation from esketamine-treated CIPN mice notably improved both the diminished PWT and DRG neuroinflammation in oxaliplatin-treated mice. Collectively, these findings suggest that repeated esketamine administration may alleviate mechanical allodynia in CIPN mice by modulating neuroinflammation, gut microbiota, and associated metabolites.

RevDate: 2025-03-07

Lukic I, Ivkovic S, Glavonic E, et al (2025)

Long-lasting Depressive Behavior of Adolescent Chronically Stressed Mice is Mediated by Gut Microbiota Dysbiosis.

Molecular neurobiology [Epub ahead of print].

Depression is one of the most common mental disorders worldwide, and its prevalence sharply rises during adolescence. Adolescence is a particularly sensitive period to the effects of environmental stressors, which can cause persistent depressive behavior extending into adulthood. However, the studies assessing if changes in gut microbiota could be one of the mediators of long-term effects of adolescent stress are scarce. In the present study, we examined enduring effects of adolescent chronic unpredictable stress (CUS) on mice behavior along with alterations in their gut microbiome, by using 16 s rRNA gene sequencing and fecal microbiota transplantation (FMT). CUS mice, as well as naïve mice receiving FMT from stressed animals, showed long-lasting anxiety and depressive-like behavior extending into adulthood. The microbiota dysbiosis in adolescence was characterized by higher abundance of Alloprevotella and lower abundance of Paraprevotella, Parasutterella, Parabacteroides, and undefined genus Rikenellaceae_RC9_gut_group. On the contrary, microbiota dysbiosis in adulthood was characterized by higher abundance of Bacteroides, Enterorhabdus, Marvinbriantia, and Parabacteroides and lower abundance of Akkermansia, Odoribacter, and Rikenella. In particular, depressive-like behavior in adolescence was negatively correlated with Paraprevotella, while depressive-like behavior in adulthood was negatively correlated with Rikenella abundance, in both CUS and FMT mice. Therefore, the transfer of microbiota from mice stressed in adolescence is able to induce long-lasting depressive-like behavior in naïve mice, clearly showing the importance of gut microbiota dysbiosis in adolescence in shaping enduring depressive behavior. Moreover, our results indicate that changes in specific but different bacteria are related to depressive behavior in adolescence and in adulthood.

RevDate: 2025-03-08

Bhalla A, Shahi A, Maity M, et al (2025)

Inflammatory Bowel Disease in Children: Current Diagnosis and Treatment Strategies.

Cureus, 17(2):e78462.

Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.

RevDate: 2025-03-09
CmpDate: 2025-03-07

Zou B, Liu S, Dong C, et al (2025)

Fecal microbiota transplantation restores gut microbiota diversity in children with active Crohn's disease: a prospective trial.

Journal of translational medicine, 23(1):288.

BACKGROUND: Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

METHODS: In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

RESULTS: At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

CONCLUSIONS: Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

TRIAL REGISTRATION: ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.

RevDate: 2025-03-09
CmpDate: 2025-03-07

Salazar-Arenas JA, Hurtado-Bermúdez LJ, Salazar-Cardona ED, et al (2025)

Clinical and microbiological profile of patients with diarrhea evaluated using the gastrointestinal panel in a high-complexity center.

BMC gastroenterology, 25(1):147.

INTRODUCTION: Gastrointestinal infections represent a worldwide public health problem. In Colombia, the incidence reaches 21.4 cases per 1,000 inhabitants. Given the limitations of traditional diagnostic methods in terms of sensitivity and specificity, the gastrointestinal panel (GIP) has emerged as a promising tool, allowing rapid detection of 22 pathogens. This study aimed to describe the clinical and microbiological characteristics of immunosuppressed and immunocompetent adult patients with diarrhea and the influence of the gastrointestinal panel in their treatment in a high-complexity hospital in Colombia.

MATERIALS AND METHODS: A cross-sectional observational study was carried out including 350 adult patients treated at the Fundación Valle del Lili hospital between 2021 and 2022. Demographic and clinical variables, GIP findings and treatment were analyzed by univariate and bivariate analysis. We compare immunocompromised and immunocompetent adult patients using Chi-square tests, Fisher's F test for qualitative variables, Student's t-test, and the Mann-Whitney U test for quantitative variables. A significance level of 5% was applied to demonstrate the significance of the variables in all the tests used.

RESULTS: The results showed that 52% were men, with an average age of 52 years. 72.0% presented acute diarrhea, being inflammatory in 60.1%. 39.1% of the patients were immunosuppressed, mainly transplant recipients (31.3%). 53% of the GIPs were positive, with up to 5 pathogens per sample. Bacteria were detected in 80%, viruses in 14.4%, and parasites in 5.5%. The most frequent bacteria were enteropathogenic E. coli (43.0%), enteroaggregative E. coli (18.6%), and C. difficile (17.4%). Norovirus was the predominant virus (67.7%) and Cryptosporidium the most common parasite (41.7%). A higher frequency of Vibrio spp. was observed in non-immunosuppressed patients (p = 0.004) and of enterotoxigenic E. coli in immunosuppressed patients. 41.0% of patients received antibiotic/antiviral therapy, 83% empirically. GIP influenced the treatment of 56.7% of patients, with a 90.0% recovery rate.

CONCLUSION: This study confirms that GIP is a valuable diagnostic tool in the management of adult patients with diarrheal disease, particularly in immunocompromised patients. In our setting it is still a costly and difficult to access test, which makes it necessary to standardize the indications for its application. Future studies could evaluate its cost-effectiveness in our context.

RevDate: 2025-03-06

Huang JN, Gao CC, Ren HY, et al (2025)

Multi-omics association pattern between gut microbiota and host metabolism of a filter-feeding fish in situ exposed to microplastics.

Environment international, 197:109360 pii:S0160-4120(25)00111-4 [Epub ahead of print].

Microplastics (MPs) are widespread in water environments and can affect gut microbiota and host metabolism of fish, but whether changes in host metabolism under MPs are mediated by gut microbiota remains unclear. Here, silver carp, a filter-feeding fish with important ecological functions, was in-situ exposure to environmentally relevant MPs. Multi-omics analysis and fecal microbiota transplantation were used to reveal the metabolic responses of carp along gut-liver-muscle axis. After three months of in situ exposure to MPs, community structure of gut microbiota of carp was reshaped, and five dominate phyla were significantly changed, including increased Cyanobacteria, Chloroflexi and Planctomycetota but decreased Firmicutes and Fusobacteriota. Weighted gene co-expression network analysis was further performed between these phyla and liver transcription spectrum, showing that the hub gene module contained up-regulated hppD, maiA and plg and activated ubiquinone and other terpenoid-quinone biosynthesis and phenylalanine metabolism. By fecal microbiota transplantation, the key gene module associated with core microbiota phyla of carp was verified in germ-free zebrafish. Interestingly, up-regulated hppD, maiA and plg and enriched phenylalanine metabolism were also observed in this module. Subsequently, metabolome performed in carp liver also shared activated phenylalanine metabolism, including increased trans-cinnamic acid and L-tyrosine. Furthermore, high-associated mapping showed that the differentially expressed metabolites (gamma-aminobutyric acid, ornithine and L-serine) related to amino acid metabolism in carp muscle were significantly accompanied with increased L-tyrosine in its liver. Overall, MPs exposure could change gut microbiome of silver carp and alter host metabolism especially amino acid metabolism along the gut-liver-muscle axis.

RevDate: 2025-03-06

Heinze T, Heimke M, Stelzner S, et al (2025)

[Surgical anatomy of the anorectum].

Chirurgie (Heidelberg, Germany) [Epub ahead of print].

The anorectum corresponds to the last segment of the gastrointestinal tract and is responsible for mediating fecal continence and controlled defecation. An understanding of the complex topographic anatomy is an indispensable prerequisite for the surgical treatment of benign and malignant diseases in the anorectal region. The detailed description of perirectal fascia, anorectal blood supply and lymph vessel drainage, pelvic autonomic nerves and components of the anal canal and anal sphincter complex has significantly contributed to improvement of the oncological and functional surgical outcome. In this article the state of knowledge relating to the anorectal anatomy is outlined providing a practical basis for rectal and proctological surgical procedures.

RevDate: 2025-03-07

Hou PF, Yao Y, Wu Y, et al (2025)

Fecal microbiota transplantation improves hepatic steatosis induced by HFD in a mouse model associated with liver ILC1 regulation and indole-3-carbinol level.

Frontiers in nutrition, 12:1500293.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased worldwide. In recent years, fecal microbiota transplantation (FMT) has become an important promising method for the treatment of MASLD. However, the mechanism remains unclear.

METHODS: The animal model with C57BL/6 male mice induced by high-fat diet (HFD) for 12 weeks has been introduced. Fecal microbiota and indole-3-carbinol (I3C) was given by oral gavage.

RESULTS: Our study demonstrated that a 6-week healthy gut microbiota transplantation tended to ameliorate hepatic steatosis and reverse the decreased liver ILC1 induced by HFD. Interestingly, there was also a negative correlation between liver ILC1 and liver TG, TC level. Furthermore, the protective effect was associated with the elevated levels of serum indole-3-carbinol (I3C). Also, a I3C administration for 6 weeks improved liver steatosis and increased the frequency of liver ILC1 induced by HFD through aryl hydrocarbon receptor (AhR) activation. Moreover, I3C binds to the residues of ALA349, PHE348, LEU309, TYR316, PHE318 on AhR through hydrogen bonds, Π bonds, hydrophobic bonds which was proved by molecular docking.

CONCLUSION: To conclude, our data demonstrated that FMT improved liver steatosis induced by HFD associated with liver ILC1 regulation and indole-3-carbinol level. The study highlighted the potential treatment value of FMT and microbiota-derived I3C in the MASLD treatment and regulation of liver ILC1 function.

RevDate: 2025-03-07

Zeng Z, Feng M, He F, et al (2024)

Gut microbiota mediates the pro-pyroptosis effect of xierezhuyubuxu decoction in hepatocellular carcinoma.

Frontiers in microbiology, 15:1481111.

INTRODUCTION: Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber". XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process.

METHODS: Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified.

RESULTS: We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD.

DISCUSSION: Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.

RevDate: 2025-03-06

Hu J, Xu F, Zhu L, et al (2025)

Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation.

Phytotherapy research : PTR [Epub ahead of print].

Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.

RevDate: 2025-03-08
CmpDate: 2025-03-05

Song Y, Li N, Jiang S, et al (2025)

Microbiota-derived H2S induces c-kit[+] cDC1 autophagic cell death and liver inflammation in metabolic dysfunction-associated steatohepatitis.

Nature communications, 16(1):2222.

Immune dysregulation-induced inflammation serves as a driving force in the progression of metabolic dysfunction-associated steatohepatitis (MASH), while the underlying cellular and molecular mechanisms remain largely uncharted. A Western diet (WD) is employed to construct mouse models of metabolic dysfunction associated steatotic liver disease (MASLD) or MASH. Mass cytometry identifies a c-kit[+] cDC1 subset whose frequency is reduced in the livers of mice and patients with MASH compared with healthy controls. Adoptive cell transfer of c-kit[+] cDC1 protects the progression of MASH. Moreover, analysis of gut microbe sequence shows that WD-fed mice and MASLD/MASH patients exhibit gut microbiota dysbiosis, with an elevated abundance of H2S-producing Desulfovibrio_sp. Transplanting of MASH-derived fecal flora, Desulfovibrio_sp., or injecting H2S intraperitoneally into MASLD mice decreases the c-kit[+]cDC1 population and exacerbates liver inflammation. Mechanistically, H2S induces autophagic cell death of cDC1 in a c-kit-dependent manner in cDC-specific c-kit[-/-] and Atg5[-/-] mice. We thus uncover that microbiota-derived H2S triggers the autophagic cell death of c-kit[+] cDC1 and ignites the liver inflammatory cascade in MASH.

RevDate: 2025-03-05

Sun W, Jia J, Liu G, et al (2025)

Polysaccharides Extracted from Old Stalks of Asparagus officinalis L. Improve Nonalcoholic Fatty Liver by Increasing the Gut Butyric Acid Content and Improving Gut Barrier Function.

Journal of agricultural and food chemistry [Epub ahead of print].

Nonalcoholic fatty liver disease (NAFLD) ranks among the most prevalent chronic liver diseases worldwide, yet effective treatments remain scarce. Old stalks of Asparagus officinalis L. are rich in polysaccharides. The anti-NAFLD mechanism of polysaccharides from old stalks of A. officinalis (AP) requires further study. Here, we studied the effects of AP on NAFLD mice and its impact on the gut microbiota. AP intervention reduces blood lipids and liver lipids and reduces liver injury and inflammation in mice with NAFLD. Moreover, AP intervention changed gut microbiota composition and increased the abundances of butyric acid-producing bacteria, thereby increasing plasma concentration of butyric acid. Furthermore, AP intervention regulated the AMPK/SREBPs signaling pathway, thereby affecting hepatic lipid synthesis. Additionally, AP intervention improved gut barrier function and reduced plasma LPS levels, which subsequently inhibited the LPS/TLR4/NF-κB signaling pathway, thereby alleviating inflammation in NAFLD model mice. Importantly, fecal microbiota transplant (FMT) outcomes demonstrated that AP-induced changes in the gut microbiota impact the AMPK/SREBPs and LPS/TLR4/NF-κB pathways. These data suggest that AP intervention ameliorates NAFLD by regulating the gut microbiota. These research provides a scientific foundation for the use of the stalks of A. officinalis in the treatment of NAFLD.

RevDate: 2025-03-06

Farah A, Paul P, Khan AS, et al (2025)

Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence.

Frontiers in medicine, 12:1435030.

INTRODUCTION: The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

METHODS: Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

RESULTS: From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

CONCLUSION: Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.

RevDate: 2025-03-06
CmpDate: 2025-03-05

Liu X, Yang K, Jia Y, et al (2025)

Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia.

Frontiers in immunology, 16:1549554.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

METHODS: The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

RESULTS: The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

CONCLUSION: Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.

RevDate: 2025-03-05

Liu FQ, An ZY, Cui LJ, et al (2025)

Correlation Between Fecal Microbiota and Corticosteroid Responsiveness in Primary Immune Thrombocytopenia: an Exploratory Study.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

Corticosteroids (CSs) are the initial therapy for immune thrombocytopenia (ITP); however, their efficacy is not adequately predicted. As a novel biomarker, the composition of the gut microbiota is non-invasively tested and altered in patients with ITP. This study aims to develop a predictive model that leverages gut microbiome data to predict the CS response in patients with ITP within the initial four weeks of treatment. Metagenomic sequencing is performed on fecal samples from 212 patients with ITP, 152 of whom underwent CS treatment and follow-up. Predictive models are trained using six machine-learning algorithms, integrating clinical indices and gut microbiome data. The support vector machine (SVM) algorithm-based model has the highest accuracy (AUC = 0.80). This model utilized a comprehensive feature set that combined clinical data (including sex, age, duration, platelet count, and bleeding scales) with selected microbial species (including Bacteroides ovatus, Bacteroides xylanisolvens, and Parabacteroides gordonii), alpha diversities, KEGG pathways, and microbial modules. This study will provide new ideas for the prediction of clinical CS efficacy, enabling informed decision-making regarding the initiation of CS or personalized treatment in patients with ITP.

RevDate: 2025-03-04

Malik S, Naqvi SAA, Shadali AH, et al (2025)

Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review.

Digestive diseases and sciences [Epub ahead of print].

BACKGROUND AND AIMS: Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs.

METHODS: We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE.

RESULTS: Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty.

CONCLUSION: Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.

RevDate: 2025-03-07
CmpDate: 2025-03-04

Wei Y, Qin L, Wu X, et al (2025)

Faecal microbiota transplantation combined with platinum-based doublet chemotherapy and tislelizumab as first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC): study protocol for a prospective, multicentre, single-arm exploratory trial.

BMJ open, 15(3):e094366.

INTRODUCTION: The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

METHODS AND ANALYSIS: FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0-1, programmed death ligand 1<50% advanced NSCLC patients, who will be given FMT by orally ingested stool capsules on the basis of standard first-line treatment of chemotherapy combined with immunotherapy. The primary endpoint of this study is the 12-month progression-free survival rate.

ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Second People's Hospital of Changzhou (number [2024] YLJSA005) and is being conducted in accordance with the principles of the Declaration of Helsinki. The results of this study will be disseminated through publication in a peer-reviewed journal and presentation at scientific conferences.

TRIAL REGISTRATION NUMBER: NCT06403111. Date of registration: 7 May 2024, the first version protocol.

RevDate: 2025-03-05

Gao J, He Y, Shi F, et al (2025)

Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.

Journal of advanced research pii:S2090-1232(25)00142-0 [Epub ahead of print].

BACKGROUND: Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.

OBJECTIVE: This study aimed to reveal the effect and potential mechanisms of ICS Ⅱ on PSD, and the role of the microbiota-gut-brain axis was investigated.

METHODS: Using middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS Ⅱ via behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).

RESULTS: ICS Ⅱ ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS Ⅱ restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-κB pathway. ICS Ⅱ significantly increased the abundance of gut microbiota (such asAkkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota's role. Mechanistically, ICS Ⅱ directly bound to Sirt6 and enhanced its activity. However, ICS Ⅱ-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.

CONCLUSION: Our findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS Ⅱ, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.

RevDate: 2025-03-04

Tian S, Kim MS, Zhao J, et al (2025)

A designed synthetic microbiota provides insight to community function in Clostridioides difficile resistance.

Cell host & microbe pii:S1931-3128(25)00055-1 [Epub ahead of print].

Clostridioides difficile, a major cause of antibiotic-associated diarrhea, is suppressed by the gut microbiome, but the precise mechanisms are not fully described. Through a meta-analysis of 12 human studies, we designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization. This lab-built 37-strain consortium formed a functional community suppressing C. difficile in vitro and in animal models. Using sFMT1 as a tractable model system, we find that bile acid 7α-dehydroxylation is not a determinant of sFMT1 efficacy while one strain performing Stickland fermentation-a pathway of competitive nutrient utilization-is both necessary and sufficient for the suppression of C. difficile, replicating the efficacy of a human fecal transplant in a gnotobiotic mouse model. Our data illustrate the significance of nutrient competition in suppression of C. difficile and a generalizable approach to interrogating complex community function through robust methods to leverage publicly available sequencing data.

RevDate: 2025-03-04

Mallick K, Khodve G, Ruwatia R, et al (2025)

Gut microbes: Therapeutic Target for neuropsychiatric disorders.

Journal of psychiatric research, 184:27-38 pii:S0022-3956(25)00111-6 [Epub ahead of print].

Neuropsychiatric diseases encompass a range of mental and neurological disorders that have a significant and far-reaching effect on an individual's quality of life. These conditions affect not only the mental status but also the physical well-being of individuals, which leads to weakened immune systems and other diseases. Emerging research underscores a significant connection between the gut microbiome and neuropsychiatric diseases, suggesting that microbial communities within the gastrointestinal tract may influence brain function and mental health. Gut dysbiosis is caused by various factors, including stress, diet, inappropriate usage of antibiotics, infections, and so on, all of which can disrupt numerous pathways, resulting in abnormal neurotransmitter signaling, inflammation, and impaired brain function. Similarly, various neuropsychiatric diseases can disrupt the specific microbiome in the gut, leading to gut dysbiosis, often impairing memory and cognitive function. The growing evidence supporting the role of gut dysbiosis in neuropsychiatric disorders has opened up new avenues for therapeutic interventions. Modulating the gut microbiome through strategies such as probiotics, prebiotics, or fecal microbiota transplantation has shown promising results in various studies of neuropsychiatric disorders. However, further research is needed to fully elucidate the mechanisms involved in gut dysbiosis-associated brain changes to develop effective and personalized treatment strategies for neuropsychiatric diseases.

RevDate: 2025-03-04

Longhitano A, Roder C, Blackmore T, et al (2025)

Australasian Society of Infectious Diseases updated guidelines for the management of Clostridioides difficile infection in adults and children in Australia and New Zealand.

Internal medicine journal [Epub ahead of print].

Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.

RevDate: 2025-03-06

Sóti Á, Nagy G, Győri Z, et al (2025)

Tension pneumothorax from large bowel herniation and perforation as a late presentation of traumatic diaphragmatic hernia during pregnancy: a case report.

International journal of emergency medicine, 18(1):40.

BACKGROUND: Diaphragmatic hernias can be congenital or acquired, with trauma being the primary cause of the latter. Both types may have delayed presentations, with abdominal organs protruding into the thoracic cavity, causing symptoms of varying severity. Pregnancy can sometimes precipitate the condition. Tension pneumothorax resulting from bowel perforation into the thorax is exceptionally rare, with only a few cases reported. To the best of the authors knowledge, this is the third documented case of a late-presenting trauma-related diaphragmatic hernia during pregnancy, complicated by tension pneumothorax.

CASE PRESENTATION: A 30-year-old woman, 29 weeks pregnant, was referred to Semmelweis University emergency department with moderate dyspnea. Initial investigation revealed tension pneumothorax. Chest tube placement released air, pus, and feces. Computer tomography identified a diaphragmatic hernia with bowel incarceration and perforation as the underlying cause. The patient underwent a delayed cesarean section and surgical repair, with a good outcome. A history of thoracic trauma eight years prior was later revealed.

CONCLUSION: Evaluating pregnant patients with shortness of breath in the emergency department is challenging. Identifying a history of thoracic or abdominal trauma is crucial, as this can raise the suspicion of diaphragmatic hernia, which can present with a wide range of symptoms. Spontaneous tension pneumothorax in pregnant women is extremely rare and requires cautious management. A multidisciplinary approach is crucial for the successful treatment of maternal diaphragmatic hernia.

RevDate: 2025-03-04

Zhang JG, Wang YW, Wang QY, et al (2025)

Clinical features and risk factors for combined Klebsiella pneumoniae infection in patients with liver cirrhosis.

World journal of hepatology, 17(2):103648.

This article discusses the findings presented by Zhang et al. They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing. In this article, we focus on the connection between chronic kidney disease and the intestinal microbiota, and propose microbiota transplantation as a potential treatment for this patient group. We also examine an intriguing phenomenon related to hepatic encephalopathy, and provide insights into the future research.

RevDate: 2025-03-04

Xie C, Cheng J, Chen P, et al (2025)

Integrating gut and IgA-coated microbiota to identify Blautia as a probiotic for enhancing feed efficiency in chickens.

iMeta, 4(1):e264.

This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a key genus linked to improved feed efficiency. Further validation demonstrated that Blautia coccoides, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production.

RevDate: 2025-03-04

Liu Y, Li H, Sun T, et al (2025)

Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.

iMeta, 4(1):e70000.

Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.

RevDate: 2025-03-05

Shi Y, Chen Z, Fang T, et al (2025)

Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities.

iMeta, 4(1):e265.

Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.

RevDate: 2025-03-06
CmpDate: 2025-03-06

Xiong Y, Lu X, Li B, et al (2025)

Bacteroides Fragilis Transplantation Reverses Reproductive Senescence by Transporting Extracellular Vesicles Through the Gut-Ovary Axis.

Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12(9):e2409740.

The diverse and dynamic population of microorganisms present in the gut microbiota may affect host health. There are evidences to support the role of gut microbiota as a key player in reproductive development. Unfortunately, the relationship between reproductive disorders caused by aging and gut microbiota remains largely unknown. Here, it is shown for the first time that gut microorganism Bacteroides fragilis (BF) transplantation ameliorates ovarian aging by transporting extracellular vesicles (EVs) through the gut-ovary axis. Mechanistically, miR-1246 is enriched in EVs derived from BF-treated intestinal cells, and these miR-1246-enriched EVs are transferred to ovaries, thereby effectively improving reproductive senescence by reducing oxidative stress in the ovaries. Specifically, miR-1246 reduces the ubiquitination of p62 and stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1-Nrf2 complex is dissociated and Keap1 is recruited to form the p62-Keap1 complex. With the dissociation of Keap1-Nrf2 complex, Nrf2 is released and activated, thus promoting the transcription of antioxidant enzymes and relieving reproductive senescence. Collectively, the data indicates that intestinal cell-derived EVs serve as natural information carriers in the crosstalk between the gut and the ovary, and intestinal microorganism transplantation is a promising approach for the treatment of ovarian dysfunction diseases.

RevDate: 2025-03-06
CmpDate: 2025-03-06

Tao W, Zhang Y, Wang B, et al (2025)

Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance.

Journal of advanced research, 69:261-278.

BACKGROUD: Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.

AIM OF REVIEW: Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.

The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.

RevDate: 2025-03-04

Marizzoni M, Tournier BB, Chevalier C, et al (2025)

Stools from a human APOEe2 donor reduces amyloid and tau pathology and increases neuroinflammation in a 3xTg AD mouse model.

Frontiers in aging neuroscience, 17:1539067.

BACKGROUND: The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer's disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology.

METHODS: FMT of bacteria isolated from stools of untreated 3xTgAD mice (M-FMT) or e2-FMT were transplanted in 15-month-old 3xTgAD mice. FMT was done alone or in combination with antibiotic and proton-pump inhibitor following the Microbiota Transfer Therapy protocol (MTT). The effect of donor (M or e2) and transplantation protocol (FMT or MTT) on hippocampal amyloid, tau pathology and neuroinflammation were assessed at the end of the treatment.

RESULTS: e2-FMT reduced amyloid, and tau pathology as well as increased neuroinflammation as compared with M-FMT. MTT was associated with reduced number of Aβ40+ plaques and tau pathology. Low levels of amyloid were associated with high levels of pro-inflammatory molecules in e2-FMT mice. These associations were partially attenuated by MTT.

CONCLUSION: Bacteria from a human APOEe2 donor reduced AD pathology and increased neuroinflammation in mice suggesting that the gut microbiota may be a mediator of the protective effect of APOEe2.

RevDate: 2025-03-03
CmpDate: 2025-03-03

Qi C, Li Z, Tu H, et al (2025)

2'-FL and cross-feeding bifidobacteria reshaped the gut microbiota of infants with atopic dermatitis ex vivo and prevented dermatitis in mice post-microbiota transplantation through retinol metabolism activation.

Gut microbes, 17(1):2474148.

2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.

RevDate: 2025-03-05
CmpDate: 2025-03-03

Guo H, Jiang H, H Liu (2025)

Case report of clostridium difficile infection after rectal resection with ileostomy.

World journal of surgical oncology, 23(1):70.

Colorectal cancer is the third most common cancer worldwide, with high incidence and mortality rates. Surgical resection is the primary treatment for rectal cancer. To reduce the occurrence and severity of postoperative complications such as anastomotic leakage, prophylactic ileostomy is often performed concurrently. However, following ileostomy creation, there is a disruption in intestinal ecology, making patients susceptible to clostridium difficile infection. clostridium difficile is a Gram-positive anaerobic spore-forming bacterium that is resistant to most antibiotics due to spore formation, leading to high recurrence rates and treatment failure. Additionally, in the early stages of clostridium difficile infection, increased ileostomy output can be challenging to differentiate from normal postoperative conditions, potentially resulting in missed diagnosis, delayed treatment, and increased healthcare burden.This case report describes a case of high out-put ileostomy caused by clostridium difficile infection following rectal resection with ileostomy, which was successfully treated by fecal microbiota transplantation, providing evidence-based medicine for clinical practice.

RevDate: 2025-03-02
CmpDate: 2025-03-02

Kushima H, H Ishii (2025)

Cryptococcosis.

Medical mycology journal, 66(1):27-31.

Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.

RevDate: 2025-03-02

Sliti A, Kim RH, Lee D, et al (2025)

Whole Genome Sequencing and In Silico Analysis of the Safety and Probiotic Features of Lacticaseibacillus paracasei FMT2 Isolated from Fecal Microbiota Transplantation (FMT) Capsules.

Microbial pathogenesis pii:S0882-4010(25)00130-5 [Epub ahead of print].

Lacticaseibacillus paracasei is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of L. paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other L. paracasei strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2,838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3,358 orthologous clusters, including 1,775 single-copy clusters, across all L. paracasei strains. Notably, L. paracasei FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of L. paracasei FMT2 for food and therapeutic applications based on its probiotic profile and safety.

RevDate: 2025-03-02

Karmisholt Grosen A, Mikkelsen S, Aas Hindhede L, et al (2025)

Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study.

The Lancet. Microbe pii:S2666-5247(24)00302-1 [Epub ahead of print].

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection.

METHODS: In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C difficile infection in patients 8 weeks after FMT.

FINDINGS: Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with C difficile infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3-12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33-0·91]; p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04-1·83]; p=0·024) and 5 or above (2·89 [1·33-6·26]; p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes.

INTERPRETATION: Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with C difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors.

FUNDING: Innovation Fund Denmark.

RevDate: 2025-03-02

Golomb SM, Guldner IH, Aleksandrovic E, et al (2025)

Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis.

Cell reports, 44(3):115356 pii:S2211-1247(25)00127-5 [Epub ahead of print].

Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.

RevDate: 2025-03-01

Petracco G, Faimann I, F Reichmann (2025)

Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.

Pharmacology & therapeutics pii:S0163-7258(25)00043-9 [Epub ahead of print].

Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.

RevDate: 2025-03-04
CmpDate: 2025-03-01

Debray R, Dickson CC, Webb SE, et al (2025)

Shared environments complicate the use of strain-resolved metagenomics to infer microbiome transmission.

Microbiome, 13(1):59.

BACKGROUND: In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. Yet, social microbiome transmission can be difficult to identify based on compositional data alone. To overcome this challenge, recent studies have used information about microbial strain sharing (i.e., the shared presence of highly similar microbial sequences) to infer transmission. However, the degree to which strain sharing is influenced by shared traits and environments among social partners, rather than transmission per se, is not well understood.

RESULTS: Here, we first use a fecal microbiota transplant dataset to show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous and recipients are sampled shortly after transmission. In contrast, in gut metagenomes from a wild baboon population, we find that demographic and environmental factors can override signals of strain sharing among social partners.

CONCLUSIONS: We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for inferring the underlying mechanisms of strain sharing and resolving true social transmission network. Video Abstract.

RevDate: 2025-02-28

Zhang W, Qi X, Han M, et al (2025)

Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota.

Ecotoxicology and environmental safety, 292:117969 pii:S0147-6513(25)00305-7 [Epub ahead of print].

Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut microbiota and investigated its underlying mechanisms. Using 16S rRNA gene sequencing, we observed significant gut microbiota dysbiosis in silicosis rats at different times (1-8 weeks), notably characterized by altered relative abundance of Ruminococcus and Lactobacillus. Fecal microbiota transplantation altered the gut microbiota structure of silicosis rats, alleviated silica-induced lung histopathological injury, with LEfSe analysis identifying Bifidobacterium as a potential biomarker. Treatment with Bifidobacterium reduced the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and fibrosis markers (collagen III, α-SMA and vimentin) in the lungs of silicosis rats, accompanied with increased serum acetic acid levels. Acetate, a major metabolite of Bifidobacterium, demonstrated similar protective effects against silicosis in this study, suggesting its role as a key mediator of Bifidobacterium action in the lungs. Both Bifidobacterium and acetate significantly upregulated Sirt1 in intestinal and lung tissues, while Sirt1 inhibition diminished their benefits to silicosis. As a widely studied histone deacetylase, Sirt1 was proven to be markedly reduced in the lungs of silicosis rats in this study. EX-527, a potent Sirt1 inhibitor, could worsen silicosis damage by upregulating the level of TGF-β1 and the degree of Smad2/3 acetylation. Our study highlights the efficacy of postbiotics, such as Bifidobacterium and acetate, and identifies Sirt1 as a promising target for silicosis treatment.

RevDate: 2025-02-28

Peng C, Lei P, Qi H, et al (2025)

Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis.

Applied and environmental microbiology [Epub ahead of print].

UNLABELLED: Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

IMPORTANCE: The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.

RevDate: 2025-02-27

Patra D, Dev G, Hand TW, et al (2025)

Friends close, enemies closer: the complex role of the microbiome in antitumor immunity.

Current opinion in immunology, 93:102537 pii:S0952-7915(25)00013-5 [Epub ahead of print].

Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.

RevDate: 2025-02-27

Tang L, Li J, Luan M, et al (2025)

Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.

Atherosclerosis, 403:119132 pii:S0021-9150(25)00029-2 [Epub ahead of print].

BACKGROUND: Gut microbiota plays a crucial role in the development and progression of atherosclerosis. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and the Edgeworthia genus, has been previously shown in our studies to attenuate atherogenesis when administered orally as an ethanolic extract (EEEG). However, the interaction between EEEG and gut microbiota, and the mechanism by which gut microbiota exerts anti-atherosclerotic effects, remains unclear.

AIMS: This study aims to determine whether the anti-atherosclerotic properties of EEEG are associated with gut microbiota remodeling.

METHOD: Atherosclerosis was induced in ApoE[-/-] mice using a high-fat diet (HFD). The mice were treated with EEEG or Lactobacillus plantarum for 16 weeks. The composition of gut microbiota was analyzed through 16S rDNA sequencing. To assess whether the anti-atherosclerotic effects of EEEG depend on the gut microbiota, HFD-fed mice were treated with a cocktail of antibiotics or underwent fecal microbiota transplantation (FMT). Simultaneously, plaque areas in the aortic roots and whole aortas of apolipoprotein E deficient (ApoE[-/-]) mice were evaluated using oil red O staining and hematoxylin-eosin staining. Serum levels of LPS, fluorescein isothiocyanate-dextran, and expression levels of tight junction proteins were measured to identify the effects of EEEG on gut barrier dysfunction in HFD-fed ApoE[-/-] mice.

RESULTS: The results revealed that EEEG treatment significantly reduced atherosclerotic lesions by ameliorating lipid accumulation and preserving gut barrier integrity. The protective effects were abrogated by antibiotics administration, concomitant with an increase in gut barrier permeability by decreasing expression of tight junction proteins. The microbial analysis indicated an augmented abundance of Lactobacillus, Turicibacter, Faecalibacterium, Akkermansia, and Desulfovibrio following EEEG treatment. Meanwhile, transplantation of fecal microbiota from EEEG-treated mice exerted the anti-atherosclerotic effect in the high-fat diet (HFD)-fed ApoE[-/-] recipient mice, accompanied by improvement of gut barrier integrity through upregulation of tight junction protein expression. Furthermore, exogenous supplementation of Lactobacillus plantarum mitigated AS in ApoE[-/-] mice and improved the gut epithelial barrier function by increasing the expression level of Zo-1.

CONCLUSION: These results suggest that the anti-atherosclerotic efficacy of EEEG is attributed to the preservation of gut barrier integrity mediated by gut microbiota. EEEG and its enriched Lactobacillus plantarum may be promising adjuncts for AS management.

IMPORTANCE: Atherosclerosis (AS) is the primary pathological basis of cardiovascular disease (CVD). The gut microbiota is known to play an important role in the development and progression of atherosclerosis. In the clinical management of AS, pharmacological classes such as antioxidants, lipid-lowering drugs, and antiplatelet agents are commonly utilized. Despite their ability to decelerate the progression of AS, complications and adverse reactions still limit their application. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and Edgeworthia Meisn genus, has been shown in previous studies to attenuate atherogenesis when orally administered as an ethanolic extract (EEEG). However, the interaction between EEEG and the gut microbiota, as well as the mechanism by which the gut microbiota exerts its anti-atherosclerotic effects, remain unclear. The significance of our research lies in identifying the mechanism behind the anti-atherosclerotic effect of Edgeworthia gardneri. The expected results will provide an important scientific basis for the clinical development and application of Edgeworthia gardneri in the prevention and treatment of AS.

RevDate: 2025-02-27

Hou S, Yu J, Li Y, et al (2025)

Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

RevDate: 2025-02-28

Yassin LK, Nakhal MM, Alderei A, et al (2025)

Exploring the microbiota-gut-brain axis: impact on brain structure and function.

Frontiers in neuroanatomy, 19:1504065.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

RevDate: 2025-03-01
CmpDate: 2025-02-26

Sedeek SA, Farowski F, Youssafi S, et al (2025)

In vitro validation concept for lyophilized fecal microbiota products with a focus on bacterial viability.

World journal of microbiology & biotechnology, 41(3):83.

Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), typically administered as a fresh or frozen stool suspension through colonoscopy, nasojejunal tube, or oral capsules. Lyophilized fecal microbiota (LFM) are an alternative to frozen FM products. We aimed to assess whether lyophilization affects bacterial viability and metabolite levels and to develop LFM capsules for clinical use in Germany. Fecal donations from pre-screened volunteers were aliquoted and analyzed through microbial cell counting, bacterial culture, 16S rRNA gene amplicon sequencing, and bile acid assays. Results showed higher counts of viable bacterial cells and cultured anaerobes in unprocessed stool compared to freshly processed stool (p = 0.012 and p < 0.001, respectively). No significant difference in viable bacterial counts was found between freshly processed (day 0), lyophilized (day 3) and frozen FM (day 3) (p = 0.15), nor between freshly processed (day 0), lyophilized (days 30 and 90) and frozen FM (day 30) (p = 0.07). lyophilization did not significantly impact bile acid and 16S rRNA profiling. Encapsulation of lyophilized powder required fewer capsules (10-14) than frozen capsules (30). LFM products are a practical, viable alternative to frozen and fresh FM products, potentially improving storage and patient acceptance.

RevDate: 2025-02-26

Li T, Chen J, Xu Y, et al (2025)

Hawthorn Pectin Alleviates DSS-Induced Colitis in Mice by Ameliorating Intestinal Barrier Function and Modulating Gut Microbiota.

Journal of agricultural and food chemistry [Epub ahead of print].

Pectin, as a kind of soluble dietary fiber in hawthorns, exhibits a wide range of biological activities. Nevertheless, its role and mechanism in ulcerative colitis (UC) remain unclear. In this study, the effect of hawthorn pectin (HP) against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanism were evaluated. HP dramatically alleviated the pathological symptoms related to colitis in mice, displaying an increase in body weight and colon length and inhibition in colon damage. Importantly, HP inhibited the serum levels of inflammation-related factors including tumor necrosis factor-α, IL-1β, and IL-6 as well as decreased the number of F4/80-positive macrophages in the colon. Moreover, the expression levels of ZO-1 and occludin proteins related to intestinal permeability were increased. A significant decrease in a dose-dependent manner at the gut bacterial genus level (such as Alistipes, Colidextribacter, and Blautia) was observed after HP treatment. HP improved the metabolic pathways of gut microbiota and increased the concentrations of short-chain fatty acids in cecal contents of UC mice. Intriguingly, fecal microbiota transplantation intervention with an HP-derived microbiome notably increased the length and relieved histopathological changes of colon in UC mice. Conclusively, our study provided valuable insights into the potential of HP as a prebiotic for maintaining intestinal health and confirmed that HP could ameliorate UC in a gut microbiota-dependent manner.

RevDate: 2025-03-01

Wei J, Chen A, Huang D, et al (2025)

Gut microbiome-derived lipopolysaccharides aggravate cognitive impairment via TLR4-mediated inflammatory signaling in neonatal rats following hypoxic-ischemic brain damage.

Brain, behavior, and immunity, 127:4-24 pii:S0889-1591(25)00069-8 [Epub ahead of print].

Hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality and neurological disabilities in children. Recent evidence indicates that gut microbiota significantly contributes to the development of inflammation and cognitive impairments following brain injury. However, the mechanisms by which gut microbiota influence inflammation and cognitive function in the neonates after HIBD are not well understood. This study established a neonatal rat model of HIBD by the classic Rice-Vannucci technique to investigate gut dysbiosis following hypoxic-ischemic (HI) insult and to elucidate the causal relationship between gut dysbiosis and cognitive impairments. Our results demonstrated that HI insult resulted in significant gut microbial dysbiosis, characterized by an expansion of Enterobacteriaceae. This dysbiosis was associated with intestinal barrier damage, lipopolysaccharides (LPS) leakage, and systemic inflammation. Conversely, administration of aminoguanidine (AG) to inhibit Enterobacteriaceae overgrowth restored intestinal barrier integrity and reduced systemic inflammation. Importantly, AG treatment effectively suppressed microglial activation, neuronal damage, and cognitive impairments in the neonatal rats subjected to HI insult. Additionally, RNA sequencing analysis revealed that differentially expressed genes in both colonic and hippocampal tissues were primarily associated with inflammation and neuronal apoptosis after HI insult. Further mechanistic exploration revealed that AG treatment mitigated intestinal LPS leakage, thereby reducing the activation of the TLR4/MyD88/NF-κB signaling pathway and production of the downstream inflammatory cytokines in both the colon and hippocampus. Notably, fecal microbiota transplantation (FMT) from the HIBD rats to the antibiotic cocktail-treated recipient rats resulted in microglial activation, neuronal damage, and cognitive impairments in the recipients. However, these adverse effects were effectively mitigated in the recipient rats that received FMT from the AG-treated donors, as well as in those undergoing hippocampal TLR4 knockdown. In conclusion, our findings indicate that LPS derived from gut Enterobacteriaceae overgrowth plays a critical role in the TLR4-mediated inflammatory signaling, providing a novel microbiota-based therapeutic approach for cognitive impairments following neonatal HIBD.

RevDate: 2025-02-26
CmpDate: 2025-02-26

Wang LL, Shen X, Xie Y, et al (2025)

A gut Eggerthella lenta-derived metabolite impairs neutrophil function to aggravate bacterial lung infection.

Science translational medicine, 17(787):eadq4409.

The composition of the gut microbiota in patients with bronchiectasis has been proven to be distinct from that of healthy individuals, and this disrupted gut microbiota can exacerbate lung infections. However, the responsible microbes and mechanisms in the "gut-lung" axis in bronchiectasis remain unknown. Here, we report that Eggerthella lenta was enriched in the gut, and taurine ursodeoxycholic acid (TUDCA) was enriched in both the guts and sera of patients with bronchiectasis, with both being associated with disease severity. Fecal microbiota transfer from patients with bronchiectasis as well as administration of E. lenta independently exacerbated pulmonary Pseudomonas aeruginosa infections in murine models. E. lenta-associated TUDCA bound adenosine monophosphate-activated protein kinase (AMPK) within neutrophils and interfered with the interaction between liver kinase B1 and AMPK, with a consequential decrease in AMPK phosphorylation. This ultimately reduced ATP production in neutrophils, inhibited their function, and compromised P. aeruginosa elimination from the lung, aggravating tissue injury. Metformin treatment improved disease severity and outcome in the mouse models. In sum, the gut bacterium E. lenta raises the stakes of bacterial lung infection because it causes dysfunction of neutrophils circulated from serum to lung via the metabolite TUDCA. Interventions targeting E. lenta or AMPK phosphorylation may serve as adjunctive strategies to complement existing approaches for managing chronic pulmonary infection in bronchiectasis and other chronic respiratory disease states.

RevDate: 2025-03-03
CmpDate: 2025-03-03

Ang TL, Koo SH, Ang D, et al (2025)

Postcholecystectomy Gut Microbiome Changes and the Clinical Impact: A Systematic Review With Narrative Synthesis.

Journal of gastroenterology and hepatology, 40(3):574-583.

BACKGROUND: Cholecystectomy (CCE) can affect the enterohepatic circulation of bile acids and result in gut microbiome changes. This systematic review aimed to clarify the effect of CCE on gut microbiome composition and its clinical impact.

METHOD: A systematic search was conducted in PubMed, Web of Science, and Scopus, combining keywords such as "cholecystectomy" or "post-cholecystectomy" with "gut microbiome," "stool microbiome," or "gut dysbiosis." Data were extracted and synthesized using narrative review. Study quality was assessed using the Newcastle-Ottawa scale.

RESULTS: A total of 1373 articles were screened and 14 studies were selected. Significant but inconsistent microbiome changes were reported. Changes were observed in alpha and beta diversity. At phylum level, an increase in Bacteroides and Ascomycota, decrease in Firmicutes, Actinomycetes, and Basidiomycota, and both increase and decrease in Fusobacteria were reported. At genus level, an increase in Prevotella and a decrease in Faecalibacterium were reported. In post-CCE diarrhea, decreased beta diversity, a decreased F/B ratio, an increase in Prevotella, an increase in Phocaeicola vulgatus, and a decrease in Prevotella copri were noted. For post-CCE syndrome, a higher abundance of Proteobacteria and decreased Firmicutes/Bacteroides (F/B) ratio were reported. A decreased relative abundance of Bifidobacterium longum subsp. longum from controls to CCE without colonic neoplasia to CCE with colonic neoplasia, and an increased abundance of Candida glabrata from controls, to CCE without colonic neoplasia and CCE with colonic neoplasia, were reported.

CONCLUSION: Patients who underwent CCE had significant gut dysbiosis. However, current studies could not clarify the detailed gut microbial structural and functional changes associated with CCE.

RevDate: 2025-03-03
CmpDate: 2025-03-03

George UE, Faleye TOC, De Coninck L, et al (2024)

Metagenomic Detection and Genetic Characterization of Human Sapoviruses among Children with Acute Flaccid Paralysis in Nigeria.

Pathogens (Basel, Switzerland), 13(3):.

Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended.

RevDate: 2025-03-01
CmpDate: 2025-02-26

Chen A, Teng C, Wei J, et al (2025)

Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.

Gut microbes, 17(1):2471015.

Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.

RevDate: 2025-02-27

Zheng J, Huang Y, Zhang L, et al (2025)

Role of the Gut-Lung Microbiome Axis in Airway Inflammation in OVA-Challenged Mice and the Effect of Azithromycin.

Journal of inflammation research, 18:2661-2676.

OBJECTIVE: This study aimed to investigate the role of the gut-lung microbiome axis in airway inflammation in asthma and to evaluate the effect of azithromycin on this axis, with a focus on the potential mechanism by which azithromycin reduces allergic airway inflammation.

METHODS: Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to assess pathological changes in the lung tissues of asthmatic mice. Leukocyte cell types in bronchoalveolar lavage fluid (BALF) samples were quantified following Wright-Giemsa staining. Total IgE, OVA-specific IgE, IL-4, IL-6, and IL-17A levels in BALF and total IgE in serum were measured by ELISA. The respiratory and gut microbiota were analysed using 16S rRNA gene sequencing and subsequent taxonomic analysis.

RESULTS: OVA-challenged asthmatic mice with gut microbiota dysbiosis exhibited alterations in the respiratory microbiota, resulting in further aggravation of airway inflammation. Following faecal microbiota transplantation (FMT) to restore gut microbiota, respiratory microbiota dysbiosis was partially improved, and airway inflammation was significantly alleviated. Furthermore, azithromycin reduced airway inflammation in asthmatic mice, particularly non-eosinophilic inflammation, for which low-dose azithromycin combined with budesonide proved more effective. Azithromycin significantly enhanced the diversity and microbial composition of the gut microbiota and also affected the respiratory microbiota. At the phylum level, azithromycin decreased the abundance of Proteobacteria in the gut microbiota. At the genus level, azithromycin reduced the abundance of Pseudomonas in the respiratory microbiota.

CONCLUSION: The gut-lung microbiome axis plays a crucial role in airway inflammation in asthma. Azithromycin may reduce airway inflammation in asthma through modulation of the gut-lung microbiome axis.

RevDate: 2025-02-26

Wang L, Zhang Z, Chen X, et al (2025)

Sakuranetin ameliorates experimental colitis in a gut microbiota-dependent manner.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 139:156540 pii:S0944-7113(25)00181-3 [Epub ahead of print].

BACKGROUND: The progression of inflammatory bowel disease (IBD) is closely connected with intestinal flora dysbiosis. Sakuranetin (SAK) is a natural compound with anti-inflammatory and antibiosis activities. We investigated the properties and mechanisms of SAK on IBD-like colitis.

METHODS: Mice with dextran sulfate sodium (DSS)-induced colitis were accomplished to assess the effects of SAK on colitis, as well as intestinal mucosal immune imbalance and intestinal barrier dysfunction. 16S rDNA was used to characterize the intestinal flora, and the short-chain fatty acid (SCFA) content in faeces was calculated using GS‒MS. Faecal microbiota transplantation (FMT) and a pseudosterile model (antibiotic cocktail, ABX) were used to evaluate whether the effects of SAK on colitis were dependent on the gut flora. Pathohistological and biochemical tests were used to estimate the safety of SAK.

RESULTS: SAK significantly ameliorated DSS-induced colitis in mice, verified by decreased weight loss, less colon shortening, and lower disease activity, histology and colonoscopy scores. Moreover, SAK alleviated gut dysbiosis and elevated the abundance of SCFA-producing bacteria in DSS-treated mice. Meanwhile, SAK increased faecal SCFA levels and activated GPR41/43 signalling. SAK also improved Treg/Th17 homeostasis and intestinal barrier function. In addition, ABX and FMT experiments confirmed that the ability of SAK to alleviate colitis was mediated through the gut flora. Finally, a safety experiment revealed that SAK had no significant adverse effects on major organ or liver/kidney function.

CONCLUSIONS: SAK may improve the intestinal immune balance and barrier function by regulating intestinal flora dysbiosis and increasing SCFA production, thereby protecting against colitis.

RevDate: 2025-02-28
CmpDate: 2025-02-26

Ge P, Guo Y, Che B, et al (2025)

Modulation of NLRP3 Inflammasome Activation by QYHT Decoction: Implications for the Treatment of Erectile Dysfunction in Hyperuricemia.

American journal of men's health, 19(1):15579883251318307.

Hyperuricemia (HUA) causes vascular endothelial dysfunction and oxidative stress, and simultaneously activates the NLRP3 inflammasome, leading to inflammatory reactions and erectile dysfunction (ED). This study aimed to investigate the effects of QYHT (Quyuhuatanerxian decoction) decoction on the NLRP3 inflammasome and explore its potential in treating HUA-induced ED. This study employed four treatment methods: (a) treating HUA-induced ED patients with QYHT and analyzing changes in gut microbiota abundance and fecal metabolites through 16S sequencing; (b) establishing an HUA-induced ED rat model, treating with different doses of QYHT, and examining changes in serum metabolites; (c) conducting fecal microbiota transplantation (FMT) therapy; evaluating erectile function, oxidative stress, inflammatory response, and NLRP3 inflammasome activation levels; and (d) exploring key monomeric compounds and potential targets in QYHT through network pharmacology and molecular docking. The treatment with QYHT and FMT increased testosterone levels, reduced oxidative stress and inflammatory marker levels, and inhibited the expressions of NLRP3-related factors. QYHT affected the gut microbiota structure and metabolite levels. The key components were linoleoyl acetate and mandanol, and the target was JAK2. QYHT decoction regulates the distribution of gut microbiota, improves amino acid metabolism, and effectively inhibits the activation of NLRP3 inflammasomes. This, in turn, enhances erectile function and reduces oxidative stress and inflammatory response levels, leading to successful treatment of HUA-induced ED.

RevDate: 2025-02-28

Parodi E, Novi M, Bottino P, et al (2025)

The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target.

Microorganisms, 13(2):.

The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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A practical handbook on fecal microbiota transplantation (FMT) for physicians, nurses, physician assistants, students, residents, and fellows, The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond provides a clinical framework to understand and administer this treatment. FMT has emerged as a promising treatment for C. difficile infection (CDI), and there is a major need for educational resources on the topic. Drs. Jessica Allegretti, Zain Kassam, and their expert contributors are leaders in the field and have collectively cared for thousands of patients suffering from recurrent CDI who have benefitted from FMT. This guide provides practical tools, clinical pearls, and answers to frequently asked questions. Beginning with introductory information on the microbiome and exploring the history of FMT, The 6 Ds of Fecal Microbiota Transplantation outlines a step-by-step checklist for administering FMT: Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?; Donor: How do you select and screen a donor for FMT?; Discussion: What are the risks, benefits, and alternatives that need to be discussed with patients?; Delivery: What is the best delivery method for FMT-colonoscopy, nasogastric tube, enema, or capsules?; Discharge and follow-up: What is the ideal post-FMT care? How should you council patients following FMT?; and Discovery: What are the most promising emerging clinical applications for FMT? What is the evidence for FMT in obesity, autism, irritable bowel syndrome, inflammatory bowel disease, antibiotic resistant bacteria, and liver disease? Arming healthcare professionals with the ability to answer questions from patients regarding FMT and the microbiome, The 6 Ds of Fecal Microbiota Transplantation provides a pragmatic guide for this exciting treatment.

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )