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31 Jul 2021 at 01:46
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Bibliography on: Human Microbiome


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RJR: Recommended Bibliography 31 Jul 2021 at 01:46 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-07-30

Avis T, Wilson FX, Khan N, et al (2021)

Targeted microbiome-sparing antibiotics.

Drug discovery today pii:S1359-6446(21)00324-X [Epub ahead of print].

A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&D) efforts, with only incremental improvements on existing broad-spectrum classes coming into clinical use recently. The disappointing returns from this approach have focussed attention on narrower-spectrum antibiotics; such new agents are directed against the pathogen of relevance with the additional benefit of preserving the human microbiome(s). Our knowledge of the gut microbiome and its contribution to health homeostasis increases yearly and suggests that broad-spectrum treatments incur health costs beyond the initial infection. Improved diagnostics, antibiotic stewardship, and the crucial role of the gut microbiome in health indicate targeted agents as a more viable approach for future antibiotic R&D.

RevDate: 2021-07-30

Ko YJ, Kim S, Pan CH, et al (2021)

Identification of functional microbial modules through network-based analysis of meta-microbial features using matrix factorization.

IEEE/ACM transactions on computational biology and bioinformatics, PP: [Epub ahead of print].

As the microbiome is composed of a variety of microbial interactions, it is imperative in microbiome research to identify a microbial sub-community that collectively conducts a specific function. However, current methodologies have been highly limited to analyzing conditional abundance changes of individual microorganisms without considering group-wise collective microbial features. To overcome this limitation, we developed a network-based method using nonnegative matrix factorization (NMF) to identify functional meta-microbial features (MMFs) that, as a group, better discriminate specific environmental conditions of samples using microbiome data. As proof of concept, large-scale human microbiome data collected from different body sites were used to identify body site-specific MMFs by applying NMF. The statistical test for MMFs led us to identify highly discriminative MMFs on sample classes, called synergistic MMFs (SYMMFs). Finally, we constructed a SYMMF-based microbial interaction network (SYMMF-net) by integrating all of the SYMMF information. Network analysis revealed core microbial modules closely related to critical sample properties. Similar results were also found when the method was applied to various disease-associated microbiome data. The developed method interprets high-dimensional microbiome data by identifying functional microbial modules on sample properties and intuitively representing their systematic relationships via a microbial network.

RevDate: 2021-07-28

Briana DD, Papaevangelou V, A Malamitsi-Puchner (2021)

The jury is still out on the existence of a placental microbiome.

Acta paediatrica (Oslo, Norway : 1992) [Epub ahead of print].

The human microbiome is crucial for regulating normal development, but the exact point when it is established remains unknown. A sterile placenta was traditionally considered a prerequisite for a healthy pregnancy, but studies have revealed that the placenta harbours microbial communities, even under normal conditions. However, reports have failed to provide evidence for the consistent presence of bacteria in the normal human placenta, challenging the in utero colonisation hypothesis. This mini-review examines our understanding of the potential placental microbial colonisation in normal healthy pregnancies. This may impact the metabolic and immune functions of the growing foetus and have long-term consequences.

RevDate: 2021-07-28

Aronson MR, Ali Akbari Ghavimi S, Gehret PM, et al (2021)

Drug-Eluting Endotracheal Tubes for Preventing Bacterial Inflammation in Subglottic Stenosis.

The Laryngoscope [Epub ahead of print].

OBJECTIVES/HYPOTHESIS: Subglottic stenosis (SGS) results from dysregulated extracellular matrix deposition by laryngotracheal fibroblasts causing scar tissue formation following intubation. Recent work has highlighted a relationship between this inflammatory state and imbalances in the upper airway microbiome. Herein, we engineer novel drug-eluting endotracheal (ET) tubes to deliver a model antimicrobial peptide Lasioglossin-III (Lasio) for the local modulation of the microbiome during intubation.

STUDY DESIGN: Controlled in vitro study.

METHODS: ET tubes were coated with a water-in-oil (w/o) emulsion of Lasio in poly(d,l-lactide-co-glycolide) (PLGA) by dipping thrice. Peptide release was quantified over 2 weeks via fluorometric peptide assays. The antibacterial activity was tested against airway microbes (Staphylococcus epidermidis, Streptococcus pneumoniae, and pooled human microbiome samples) by placing Lasio/PLGA-coated tubes and appropriate controls in 48 well plates with diluted bacteria. Bacterial inhibition and tube adhesion were tested by measuring optical density and colony formation after tube culture, respectively. Biocompatibility was tested against laryngotracheal fibroblasts and lung epithelial cells.

RESULTS: We achieved a homogeneous coating of ET tubes with Lasio in a PLGA matrix that yields a prolonged, linear release over 1 week (typical timeframe before the ET tube is changed). We observed significant antibacterial activity against S. epidermidis, S. pneumoniae, and human microbiome samples, and prevention of bacterial adherence to the tube. Additionally, the released Lasio did not cause any cytotoxicity toward laryngotracheal fibroblasts or lung epithelial cells in vitro.

CONCLUSION: Overall, we demonstrate the design of an effective-eluting ET tube to modulate upper-airway bacterial infections during intubation which could be deployed to help prevent SGS.

LEVEL OF EVIDENCE: N/A Laryngoscope, 2021.

RevDate: 2021-07-27

Heinken A, Basile A, Hertel J, et al (2021)

Genome-Scale Metabolic Modeling of the Human Microbiome in the Era of Personalized Medicine.

Annual review of microbiology [Epub ahead of print].

The human microbiome plays an important role in human health and disease. Meta-omics analyses provide indispensable data for linking changes in microbiome composition and function to disease etiology. Yet, the lack of a mechanistic understanding of, e.g., microbiome-metabolome links hampers the translation of these findings into effective, novel therapeutics. Here, we propose metabolic modeling of microbial communities through constraint-based reconstruction and analysis (COBRA) as a complementary approach to meta-omics analyses. First, we highlight the importance of microbial metabolism in cardiometabolic diseases, inflammatory bowel disease, colorectal cancer, Alzheimer disease, and Parkinson disease. Next, we demonstrate that microbial community modeling can stratify patients and controls, mechanistically link microbes with fecal metabolites altered in disease, and identify host pathways affected by the microbiome. Finally, we outline our vision for COBRA modeling combined with meta-omics analyses and multivariate statistical analyses to inform and guide clinical trials, yield testable hypotheses, and ultimately propose novel dietary and therapeutic interventions. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

RevDate: 2021-07-27

Lichtenstein M, Turjerman S, Pinto JM, et al (2021)

Pathophysiology of SARS-CoV-2 Infection in the Upper Respiratory Tract and Its Relation to Breath Volatile Organic Compounds.

mSystems [Epub ahead of print].

Among the many products of metabolic processes are volatile organic compounds (VOCs). In the airways, these volatile metabolites are emitted through breathing and thus are easily sampled for analysis. Recent work has connected the functions and structure of the human microbiome with health and disease. Alteration in microbial function in this context can result in differences in metabolite composition, including that of VOCs, presenting the possibility of a new noninvasive method for clinical diagnosis. Screening methods that assess VOCs arising from changes in the airway microbiome could be highly useful in diagnosing viral upper respiratory tract infections (URTIs), e.g., COVID-19, which are highly contagious and have an enormous public health impact worldwide. A rapid noninvasive screening test for URTIs would pose major advantages in containing the disease. As early evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the human microbiome (both in the gut and the respiratory tract), we propose that detection of a VOC signature of an altered nasal microbiome could be fruitful as a rapid noninvasive measure of URTI in general and of SARS-CoV-2 in particular.

RevDate: 2021-07-23

Gawlik A, Salonen A, Jian C, et al (2021)

Personalized approach to childhood obesity: Lessons from gut microbiota and omics studies. Narrative review and insights from the 29th European childhood obesity congress.

Pediatric obesity [Epub ahead of print].

The traditional approach to childhood obesity prevention and treatment should fit most patients, but misdiagnosis and treatment failure could be observed in some cases that lie away from average as part of individual variation or misclassification. Here, we reflect on the contributions that high-throughput technologies such as next-generation sequencing, mass spectrometry-based metabolomics and microbiome analysis make towards a personalized medicine approach to childhood obesity. We hypothesize that diagnosing a child as someone with obesity captures only part of the phenotype; and that metabolomics, genomics, transcriptomics and analyses of the gut microbiome, could add precision to the term "obese," providing novel corresponding biomarkers. Identifying a cluster -omic signature in a given child can thus facilitate the development of personalized prognostic, diagnostic, and therapeutic approaches. It can also be applied to the monitoring of symptoms/signs evolution, treatment choices and efficacy, predisposition to drug-related side effects and potential relapse. This article is a narrative review of the literature and summary of the main observations, conclusions and perspectives raised during the annual meeting of the European Childhood Obesity Group. Authors discuss some recent advances and future perspectives on utilizing a systems approach to understanding and managing childhood obesity in the context of the existing omics data.

RevDate: 2021-07-23

Andrade BGN, Goris T, Afli H, et al (2021)

Putative mobilized colistin resistance genes in the human gut microbiome.

BMC microbiology, 21(1):220.

BACKGROUND: The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes.

RESULTS: A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings.

CONCLUSION: This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.

RevDate: 2021-07-27

Sumibcay TJ, Lee-Jayaram JJ, LG Yamamoto (2021)

Reducing Broad-Spectrum Antibiotic Treatment of Simple Group A Streptococcal Infections to Reduce Harm to the Microbiome.

Cureus, 13(6):e15629.

Background Broad-spectrum antibiotics disrupt the human microbiome resulting in a greater risk of harmful, long-term conditions that impact human health. Group A streptococcal (GAS) infections can be treated with penicillin. Objective We examined the treatment of simple GAS infections to assess the use of broad-spectrum antibiotics. Methods Smart relational database extraction queries from January 1, 2016 to July 10, 2019 (3.6 years) of patients less than 22 years old in a 4-hospital system electronic medical record (EMR). Results We found 1778 non-ED outpatients and 873 ED patients with simple GAS infections who were not allergic to penicillin. A total of 75% and 44% of non-ED and ED patients were treated with broad-spectrum antibiotics, respectively (p < 0.001). Older patients were treated with penicillin alone more frequently than younger age groups (p < 0.001). Conclusion These findings highlight opportunities for clinicians to reduce the utilization of broad-spectrum antibiotics for the treatment of simple GAS infections to reduce harm to the microbiome.

RevDate: 2021-07-26

Hyun DW, Lee JY, Kim MS, et al (2021)

Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.

Journal of microbiology (Seoul, Korea), 59(8):792-806.

Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.

RevDate: 2021-07-21

Zhang XS, Yin YS, Wang J, et al (2021)

Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.

Cell host & microbe pii:S1931-3128(21)00296-1 [Epub ahead of print].

Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here, we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut-microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury.

RevDate: 2021-07-21

Diebold PJ, New FN, Hovan M, et al (2021)

Linking plasmid-based beta-lactamases to their bacterial hosts using single-cell fusion PCR.

eLife, 10: pii:66834.

The horizonal transfer of plasmid-encoded genes allows bacteria to adapt to constantly shifting environmental pressures, bestowing functional advantages to their bacterial hosts such as antibiotic resistance, metal resistance, virulence factors, and polysaccharide utilization. However, common molecular methods such as short- and long-read sequencing of microbiomes cannot associate extrachromosomal plasmids with the genome of the host bacterium. Alternative methods to link plasmids to host bacteria are either laborious, expensive, or prone to contamination. Here we present the One-step Isolation and Lysis PCR (OIL-PCR) method, which molecularly links plasmid-encoded genes with the bacterial 16S rRNA gene via fusion PCR performed within an emulsion. After validating this method, we apply it to identify the bacterial hosts of three clinically relevant beta-lactamases within the gut microbiomes of neutropenic patients, as they are particularly vulnerable multidrug-resistant infections. We successfully detect the known association of a multi-drug resistant plasmid with Klebsiella pneumoniae, as well as the novel associations of two low-abundance genera, Romboutsia and Agathobacter. Further investigation with OIL-PCR confirmed that our detection of Romboutsia is due to its physical association with Klebsiella as opposed to directly harboring the beta-lactamase genes. Here we put forth a robust, accessible, and high-throughput platform for sensitively surveying the bacterial hosts of mobile genes, as well as detecting physical bacterial associations such as those occurring within biofilms and complex microbial communities.

RevDate: 2021-07-20

Brubaker L, Gourdine JF, Siddiqui NY, et al (2021)

Forming Consensus To Advance Urobiome Research.

mSystems [Epub ahead of print].

Urobiome research has the potential to advance the understanding of a wide range of diseases, including lower urinary tract symptoms and kidney disease. Many scientific areas have benefited from early research method consensus to facilitate the greater, common good. This consensus document, developed by a group of expert investigators currently engaged in urobiome research (UROBIOME 2020 conference participants), aims to promote standardization and advances in this field by the adoption of common core research practices. We propose a standardized nomenclature as well as considerations for specimen collection, preservation, storage, and processing. Best practices for urobiome study design include our proposal for standard metadata elements as part of core metadata collection. Although it is impractical to follow fixed analytical procedures when analyzing urobiome data, we propose guidelines to document and report data originating from urobiome studies. We offer this first consensus document with every expectation of subsequent revision as our field progresses.

RevDate: 2021-07-20

Gargiulo Isacco C, Inchingolo AD, Nguyen Cao KD, et al (2021)

The bad relationship, osteo-decay and diabetes type 2 searching for a link: a literature review.

Journal of biological regulators and homeostatic agents, 35(2 Suppl. 1):253-269.

The diabetes and osteoporotic metabolic diseases are characterized by a wide prevalence of the population worldwide and correlated to alteration of the bone tissues. Several cofactors could influence the clinical course and the biochemistry of the pathologies such as human microbiome, nutrition characteristics, gut microbiota activity and interactions with vitamin K and D across IGF/GH and TP53 signaling pathways and the glucose/energy as mechanism for bone tissue health. Moreover, also the calories and sugar consumption seem to be correlated to an increased inflammatory state with several consequences for hematopoiesis and host tissues response. The aim of the present literature review was to highlight the role of osteoporotic diseases and diabetes type 2 link for the bone metabolism. The literature cases showed that a correlation between bone-gut-kidney-heart-CNS-Immunity crosstalk seems to be linked with bone metabolism and health regulation. Moreover, also the aging process could represent a valuable co-factor for the sustaining of the metabolic disorders upon a multi-systemic level.

RevDate: 2021-07-19

Di Guglielmo MD, Franke K, Cox C, et al (2019)

Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort.

Human microbiome journal, 12:.

Background: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short-term or long-term composition and function of the gut microbiome.

Results: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence or absence of species identified in their gut microbiome. Thirty-two genera were identified as statistically different in the gut microbiome sequenced between BF and FF infants. Furthermore, the computational workflow identified 371 bacterial genes that were statistically different between the BF and FF cohorts in abundance. Only seven genes were lower in abundance (or absent) in the FF cohort compared to the BF cohort, including CRISPR/Cas9; whereas, the remaining candidates, including autotransporter adhesins, were higher in abundance in the FF cohort compared to BF cohort.

Conclusions: These studies demonstrated that FF infants have, at an early age, a significantly different gut microbiome with potential implications for function of the fecal microbiota. Interactions between the fecal microbiota and host hinted at here have been linked to numerous diseases. Determining whether these non-abundant or more abundant genes have biological consequence related to infant feeding may aid in understanding the adult gut microbiome, and the pathogenesis of obesity.

RevDate: 2021-07-17

Hammond AM, Monir RL, JJ Schoch (2021)

The role of the pediatric cutaneous and gut microbiomes in childhood disease: A review.

Seminars in perinatology pii:S0146-0005(21)00066-5 [Epub ahead of print].

OBJECTIVE: Infancy and early childhood are crucial periods in the development of the human microbiome and shape the trajectory of microbial colonization, immune system development, and systemic disease. We review the development of the skin and gut microbiomes, their connection to the immune system, and their relevance to common pediatric pathologies.

FINDINGS: Beginning after birth, and likely even in utero, colonization of the skin and the gut occur in parallel, influenced by external factors. This colonization, in turn, dictates maturation of the immune system and contributes to conditions from atopic dermatitis to sepsis. Emerging literature is identifying links between the gut and skin microbiomes.

CONCLUSION: The gut and skin microbiomes are associated with pediatric disease states. Immune and microbial plasticity make this unique period an ideal target for intervention. Investigating the purposeful manipulation of the pediatric microbiome may lead to novel treatment and prevention strategies.

RevDate: 2021-07-16

Bai J, Zhang W, Z Amirkhanzadeh Barandouzir (2021)

Human Microbiome: Understanding the Role of the Gut Microbiome and Implications for Oncology Nursing Care.

Clinical journal of oncology nursing, 25(4):383-387.

By understanding the human microbiome and its influencing factors, oncology nurses in clinical practice can educate, screen, and monitor patients with cancer who have a higher risk of gut microbiome dysbiosis. Knowledge of the gut microbiome and its impact on cancer outcomes can help oncology nurses interpret associations between the gut microbiome and treatment- related toxicities and symptoms. Oncology nurses can guide patients to build a healthy gut microbiome across the trajectory of cancer treatment and survivorship.

RevDate: 2021-07-16

Javier-DesLoges J, McKay RR, Swafford AD, et al (2021)

The microbiome and prostate cancer.

Prostate cancer and prostatic diseases [Epub ahead of print].

There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are several potential pathways for microbiome-based mechanisms for the development of prostate cancer: direct impacts of microbes or microbial products in the prostate or the urine, and indirect impacts from microbes or microbial products in the gastrointestinal tract. Unique microbial signatures have been identified within the stool, oral cavity, tissue, urine, and blood of prostate cancer patients, but studies vary in their findings. Recent studies describe potential diagnostic and therapeutic applications of the microbiome, but further clinical investigation is needed. In this review, we explore the existing literature on the discovery of the human microbiome and its relationship to prostate cancer.

RevDate: 2021-07-15

Han S, Van Treuren W, Fischer CR, et al (2021)

A metabolomics pipeline for the mechanistic interrogation of the gut microbiome.

Nature, 595(7867):415-420.

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules1-3, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.

RevDate: 2021-07-15

Karcher N, Nigro E, Punčochář M, et al (2021)

Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly.

Genome biology, 22(1):209.

BACKGROUND: Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.

RESULTS: We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.

CONCLUSIONS: We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.

RevDate: 2021-07-14

McCoubrey LE, Gaisford S, Orlu M, et al (2021)

Predicting drug-microbiome interactions with machine learning.

Biotechnology advances pii:S0734-9750(21)00103-8 [Epub ahead of print].

Pivotal work in recent years has cast light on the importance of the human microbiome in maintenance of health and physiological response to drugs. It is now clear that gastrointestinal microbiota have the metabolic power to promote, inactivate, or even toxify the efficacy of a drug to a level of clinically relevant significance. At the same time, it appears that drug intake has the propensity to alter gut microbiome composition, potentially affecting health and response to other drugs. Since the precise composition of an individual's microbiome is unique, one's drug-microbiome relationship is similarly unique. Thus, in the age of evermore personalised medicine, the ability to predict individuals' drug-microbiome interactions is highly sought. Machine learning (ML) offers a powerful toolkit capable of characterising and predicting drug-microbiota interactions at the individual patient level. ML techniques have the potential to learn the mechanisms operating drug-microbiome activities and measure patients' risk of such occurrences. This review will outline current knowledge at the drug-microbiota interface, and present ML as a technique for examining and forecasting personalised drug-microbiome interactions. When harnessed effectively, ML could alter how the pharmaceutical industry and healthcare professionals consider the drug-microbiome axis in patient care.

RevDate: 2021-07-13

Jian C, Carpén N, Helve O, et al (2021)

Early-life gut microbiota and its connection to metabolic health in children: Perspective on ecological drivers and need for quantitative approach.

EBioMedicine, 69:103475 pii:S2352-3964(21)00268-1 [Epub ahead of print].

The colonisation and development of the gut microbiota has been implicated in paediatric metabolic disorders via its powerful effect on host metabolic and immune homeostasis. Here we summarise the evidence from human studies on the early gut microbiota and paediatric overweight and obesity. Manipulation of the early gut microbiota may represent a promising target for countering the burgeoning metabolic disorders in the paediatric population, provided the assembly patterns of microbiota and their health consequences can be decoded. Therefore, in this review, we pay particular attention to the important ecological drivers affecting the community dynamics of the early gut microbiota. We then discuss the knowledge gaps in commonly studied exposures linking the gut microbiota to metabolic disorders, especially regarding maternal factors and antibiotic use. This review also attempts to give directions for future studies aiming to identify predictive and corrective measures for paediatric metabolic disorders based on the gut microbiota. Gut microbiota; Metabolism; Paediatric overweight and obesity; Ecological driver; Dynamics; Infants.

RevDate: 2021-07-13

Wastyk HC, Fragiadakis GK, Perelman D, et al (2021)

Gut-microbiota-targeted diets modulate human immune status.

Cell pii:S0092-8674(21)00754-6 [Epub ahead of print].

Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.

RevDate: 2021-07-13

Kostopoulos I, Aalvink S, Kovatcheva-Datchary P, et al (2021)

A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo.

Frontiers in microbiology, 12:632454.

The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.

RevDate: 2021-07-12

Koskenvuo L, Lunkka P, Varpe P, et al (2021)

Mechanical bowel preparation and oral antibiotics versus mechanical bowel preparation only prior rectal surgery (MOBILE2): a multicentre, double-blinded, randomised controlled trial-study protocol.

BMJ open, 11(7):e051269 pii:bmjopen-2021-051269.

INTRODUCTION: Mechanical bowel preparation (MBP) prior to rectal surgery is widely used. Based on retrospective data many guidelines recommend mechanical and oral antibiotic bowel preparation (MOABP) to reduce postoperative complications and specifically surgical site infections (SSIs). The primary aim of this study is to examine whether MOABP reduces complications of rectal surgery.

METHODS AND ANALYSIS: The MOBILE2 (Mechanical Bowel Preparation and Oral Antibiotics vs Mechanical Bowel Preparation Only Prior Rectal Surgery) trial is a multicentre, double-blinded, parallel group, superiority, randomised controlled trial comparing MOABP to MBP among patients scheduled for rectal surgery with colorectal or coloanal anastomosis. The patients randomised to the MOABP group receive 1 g neomycin and 1 g metronidazole two times on a day prior to surgery and patients randomised to the MBP group receive identical placebo. Based on power calculations, 604 patients will be enrolled in the study. The primary outcome is Comprehensive Complication Index within 30 days after surgery. Secondary outcomes are SSIs within 30 days after surgery, the number and classification of anastomosis dehiscences, the length of hospital stay, mortality within 90 days after surgery and the number of patients who received adjuvant treatment if needed. Tertiary outcomes are overall survival, disease-specific survival, recurrence-free survival and difference in quality-of-life before and 1 year after surgery. In addition, the microbiota differences in colon mucosa are analysed.

ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.


RevDate: 2021-07-09

Tuganbaev T, K Honda (2021)

Non-zero-sum microbiome immune system interactions.

European journal of immunology [Epub ahead of print].

Fundamental asymmetries between the host and its microbiome in enzymatic activities and nutrient storage capabilities have promoted mutualistic adaptations on both sides. As a result, the enteric immune system has evolved so as not to cause a zero-sum sterilization of non-self, but rather achieve a non-zero-sum self-reinforcing cooperation with its evolutionary partner the microbiome. In this review we attempt to integrate the accumulated knowledge of immune - microbiome interactions into an evolutionary framework and trace the pattern of positive immune - microbiome feedback loops across epithelial, enteric nervous system, innate and adaptive immune circuits. Indeed, the immune system requires commensal signals for its development and function, and reciprocally protects the microbiome from nutrient shortage and pathogen outgrowth. In turn, a healthy microbiome is the result of immune system curatorship as well as microbial ecology. The paradigms of host-microbiome asymmetry and the cooperative nature of their interactions identified in the gut are applicable across all tissues influenced by microbial activities. Incorporation of immune system influences into models of microbiome ecology will be a step forward towards defining what constitutes a healthy human microbiome and guide discoveries of novel host-microbiome mutualistic adaptations that may be harnessed for promotion of human health. This article is protected by copyright. All rights reserved.

RevDate: 2021-07-10

Young RB, Marcelino VR, Chonwerawong M, et al (2021)

Key Technologies for Progressing Discovery of Microbiome-Based Medicines.

Frontiers in microbiology, 12:685935.

A growing number of experimental and computational approaches are illuminating the "microbial dark matter" and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.

RevDate: 2021-07-12
CmpDate: 2021-07-12

Paglia L (2021)

From native core micriobiome to milk-oriented microbiome.

European journal of paediatric dentistry, 22(2):89.

The human microbiome is the full set of microorganisms (microbiota) present on and in our body. Its importance is such that the human being has been defined as a holobiont, that is, a superorganism made up of human eukaryotic cells and microbial cells. A balanced microbiota (eubiosis) is a prerequisite for health and well-being; on the contrary, an altered microbiota (dysbiosis) is the cause of pathological conditions. This concept is the cornerstone of the "microbiota revolution": Currently there is no disease that cannot be re- interpreted as a function of microbiome. While all human beings have similar DNA, it is the microbiome that make every person genetically unique; therefore the microbiome is the variable component of the genome which characterises each one of us. About one third of the microbiome is common to all individuals, while two thirds are specific to each subject and constitute a sort of fingerprint that forms and stabilises in the first 2-3 years of life. This timeframe is extremely important since it has been shown that the structure of the microbiome is already acquired in the embryonic-fetal period, it is completed within 3 years and lasts a lifetime. The native core microbiome is the first microbiota and characterises individuals for their whole life. It is affected by four main variables: The quality of family and social life of the mother-to-be, the intake of drugs during pregnancy, as well as the type of birth and breastfeeding. It is renowned that breast milk is a complex, unique and essential food for the growth of the child, but one of its functions - which is still under investigation today - is to feed and guide the formation of the microbiome of the newborn even after the introduction of solid foods, during the first 3 years of life. This function is carried out by the over one hundred different types of oligosaccharides that are present in breast milk, which is why these days we talk about the so-called MOM (milk-oriented microbiome). The correct formation of the microbiome affects the entire life of an individual. This is a more than valid reason to promote breastfeeding even after eruption of baby teeth and throughout the weaning period. The role of pediatric dentists, together with hygienists and pediatricians, is to spread and stress out the importance of oral hygiene so that breastfeeding can only bring benefits and not carious lesions!

RevDate: 2021-07-11

Jones J, Reinke SN, Ali A, et al (2021)

Fecal sample collection methods and time of day impact microbiome composition and short chain fatty acid concentrations.

Scientific reports, 11(1):13964.

Associations between the human gut microbiome and health outcomes continues to be of great interest, although fecal sample collection methods which impact microbiome studies are sometimes neglected. Here, we expand on previous work in sample optimization, to promote high quality microbiome data. To compare fecal sample collection methods, amplicons from the bacterial 16S rRNA gene (V4) and fungal (ITS2) region, as well as short chain fatty acid (SCFA) concentrations were determined in fecal material over three timepoints. We demonstrated that spot sampling of stool results in variable detection of some microbial members, and inconsistent levels of SCFA; therefore, sample homogenization prior to subsequent analysis or subsampling is recommended. We also identify a trend in microbial and metabolite composition that shifts over two consecutive stool collections less than 25 h apart. Lastly, we show significant differences in bacterial composition that result from collecting stool samples in OMNIgene·Gut tube (DNA Genotec) or Stool Nucleic Acid Collection and Preservation Tube (NORGEN) compared to immediate freezing. To assist with planning fecal sample collection and storage procedures for microbiome investigations with multiple analyses, we recommend participants to collect the first full bowel movement of the day and freeze the sample immediately after collection.

RevDate: 2021-07-08

Liao B, Ye X, Chen X, et al (2021)

The two-component signal transduction system and its regulation in Candida albicans.

Virulence, 12(1):1884-1899.

Candida albicans, which can cause superficial and life-threatening systemic infections, is the most common opportunistic fungal pathogen in the human microbiome. The two-component system is one of the most important C. albicans signal transduction pathways, regulating the response to oxidative and osmotic stresses, adhesion, morphogenesis, cell wall synthesis, virulence, drug resistance, and the host-pathogen interactions. Notably, some components of this signaling pathway have not been found in the human genome, indicating that the two-component system of C. albicans can be a potential target for new antifungal agents. Here, we summarize the composition, signal transduction, and regulation of the two-component system of C. albicans to emphasize its essential roles in the pathogenesis of C. albicans and the new therapeutic target for antifungal drugs.

RevDate: 2021-07-06

Cabrera LE, Pekkarinen PT, Alander M, et al (2021)

Characterization of low-density granulocytes in COVID-19.

PLoS pathogens, 17(7):e1009721 pii:PPATHOGENS-D-21-00905 [Epub ahead of print].

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.

RevDate: 2021-07-06

Schwierzeck V, Hülpüsch C, M Reiger (2021)

Microbiome of Barrier Organs in Allergy: Who Runs the World? Germs!.

Handbook of experimental pharmacology [Epub ahead of print].

Over the last few decades, allergic diseases have been steadily increasing worldwide, a phenomenon that is not yet completely understood. Recent evidence, however, suggests that alterations in the microbiome may be a contributing factor. The microbiome refers to all microorganisms in a habitat including bacteria, fungi, and viruses. Using modern sequencing technologies, we are now capable of detecting and analyzing the human microbiome in more detail than ever before. Epidemiological and experimental studies have indicated that a complex intestinal microbiome supports the development of the immune system during childhood, thus providing protection from allergic diseases, including food allergy. The microbiome becomes an important part of human physiology and forms dynamic relationships with our various barrier systems. For example, bacterial dysbiosis is a hallmark of atopic eczema and correlates with disease progression. Similarly, the lung and nasopharyngeal microbiome is altered in patients with asthma and allergic rhinitis. While these results are interesting, the underlying mechanisms are still unclear and need to be investigated with functional studies. This review gives a short overview of the terminology and methods used in microbiome research before highlighting results concerning the lung, skin, and intestinal microbiome in allergic diseases.

RevDate: 2021-07-05

Saha D, Ota MOC, Pereira P, et al (2021)

Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment.

Expert review of vaccines [Epub ahead of print].

INTRODUCTION: As of January 2021, rotavirus vaccination programs have been implemented in 109 countries and their use has resulted in a positive impact on rotavirus-related diarrheal hospitalizations and mortality in children below five years of age. Despite these successes, several countries in Africa and Asia where disease burden is high have not yet implemented rotavirus vaccination at all or at a scale sufficient enough to demonstrate impact. This could be, among other reasons, due to poor vaccine coverage and the modest levels of efficacy and effectiveness of the vaccines in these resource-limited settings.

AREAS COVERED: We review various factors related to the human host (malnutrition, maternally-derived antibodies and breastfeeding, genetic factors, blood group and co-administration with oral polio vaccine), rotavirus pathogen (force of infection, strain diversity and coinfections) and the environment (related to the human microbiome) which reflect complex and interconnected processes leading to diminished vaccine performance in resource-limited settings.

EXPERT OPINION: Addressing the limiting factors for vaccine efficacy is needed but likely to take a long time to be resolved. An immediate solution is to increase the immunization coverage to higher values generating an overall effect of adequate proportion of protected population to reduce the prevalence of rotavirus disease.

RevDate: 2021-07-06

DiMucci D, Kon M, D Segrè (2021)

BowSaw: Inferring Higher-Order Trait Interactions Associated With Complex Biological Phenotypes.

Frontiers in molecular biosciences, 8:663532.

Machine learning is helping the interpretation of biological complexity by enabling the inference and classification of cellular, organismal and ecological phenotypes based on large datasets, e.g., from genomic, transcriptomic and metagenomic analyses. A number of available algorithms can help search these datasets to uncover patterns associated with specific traits, including disease-related attributes. While, in many instances, treating an algorithm as a black box is sufficient, it is interesting to pursue an enhanced understanding of how system variables end up contributing to a specific output, as an avenue toward new mechanistic insight. Here we address this challenge through a suite of algorithms, named BowSaw, which takes advantage of the structure of a trained random forest algorithm to identify combinations of variables ("rules") frequently used for classification. We first apply BowSaw to a simulated dataset and show that the algorithm can accurately recover the sets of variables used to generate the phenotypes through complex Boolean rules, even under challenging noise levels. We next apply our method to data from the integrative Human Microbiome Project and find previously unreported high-order combinations of microbial taxa putatively associated with Crohn's disease. By leveraging the structure of trees within a random forest, BowSaw provides a new way of using decision trees to generate testable biological hypotheses.

RevDate: 2021-07-02

Hu J, Wang C, Blaser MJ, et al (2021)

Joint modeling of zero-inflated longitudinal proportions and time-to-event data with application to a gut microbiome study.

Biometrics [Epub ahead of print].

Recent studies have suggested that the temporal dynamics of the human microbiome may have associations with human health and disease. An increasing number of longitudinal microbiome studies, which record time to disease onset, aim to identify candidate microbes as biomarkers for prognosis. Owing to the ultra-skewness and sparsity of microbiome proportion (relative abundance) data, directly applying traditional statistical methods may result in substantial power loss or spurious inferences. We propose a novel joint modeling framework [JointMM], which is comprised of two sub-models: a longitudinal sub-model called zero-inflated scaled-Beta generalized linear mixed-effects regression to depict the temporal structure of microbial proportions among subjects; and a survival sub-model to characterize the occurrence of an event and its relationship with the longitudinal microbiome proportions. JointMM is specifically designed to handle the zero-inflated and highly skewed longitudinal microbial proportion data and examine whether the temporal pattern of microbial presence and/or the non-zero microbial proportions are associated with differences in the time to an event. The longitudinal sub-model of JointMM also provides the capacity to investigate how the (time-varying) covariates are related to the temporal microbial presence/absence patterns and/or the changing trend in non-zero proportions. Comprehensive simulations and real data analyses are used to assess the statistical efficiency and interpretability of JointMM. This article is protected by copyright. All rights reserved.

RevDate: 2021-07-02

Sharma D, W Xu (2021)

phyLoSTM: a novel deep learning model on disease prediction from longitudinal microbiome data.

Bioinformatics (Oxford, England) pii:6313160 [Epub ahead of print].

MOTIVATION: Research shows that human microbiome is highly dynamic on longitudinal timescales, changing dynamically with diet, or due to medical interventions. In this paper, we propose a novel deep learning framework "phyLoSTM", using a combination of Convolutional Neural Networks and Long Short Term Memory Networks (LSTM) for feature extraction and analysis of temporal dependency in longitudinal microbiome sequencing data along with host's environmental factors for disease prediction. Additional novelty in terms of handling variable timepoints in subjects through LSTMs, as well as, weight balancing between imbalanced cases and controls is proposed.

RESULTS: We simulated 100 datasets across multiple time points for model testing. To demonstrate the model's effectiveness, we also implemented this novel method into two real longitudinal human microbiome studies: (i) DIABIMMUNE three country cohort with food allergy outcomes (Milk, Egg, Peanut and Overall) (ii) DiGiulio study with preterm delivery as outcome. Extensive analysis and comparison of our approach yields encouraging performance with an AUC of 0.897 (increased by 5%) on simulated studies and AUCs of 0.762 (increased by 19%) and 0.713 (increased by 8%) on the two real longitudinal microbiome studies respectively, as compared to the next best performing method, Random Forest. The proposed methodology improves predictive accuracy on longitudinal human microbiome studies containing spatially correlated data, and evaluates the change of microbiome composition contributing to outcome prediction.


RevDate: 2021-07-02

Pultar F, Hansen ME, Wolfrum S, et al (2021)

Mutanobactin D from the Human Microbiome: Total Synthesis, Configurational Assignment, and Biological Evaluation.

Journal of the American Chemical Society [Epub ahead of print].

Mutanobactin D is a non-ribosomal, cyclic peptide isolated from Streptococcus mutans and shows activity reducing yeast-to-hyphae transition as well as biofilm formation of the pathogenic yeast Candida albicans. We report the first total synthesis of this natural product, which relies on enantioselective, zinc-mediated 1,3-dipolar cycloaddition and a sequence of cascading reactions, providing the key lipidated γ-amino acid found in mutanobactin D. The synthesis enables configurational assignment, determination of the dominant solution-state structure, and studies to assess the stability of the lipopeptide substructure found in the natural product. The information stored in the fingerprint region of the IR spectra in combination with quantum chemical calculations proved key to distinguishing between epimers of the α-substituted β-keto amide. Synthetic mutanobactin D drives discovery and analysis of its effect on growth of other members of the human oral consortium. Our results showcase how total synthesis is central for elucidating the complex network of interspecies communications of human colonizers.

RevDate: 2021-07-10

Déjean G, Tudela H, Bruno L, et al (2021)

Identifying a Novel Bile Salt Hydrolase from the Keystone Gut Bacterium Christensenella minuta.

Microorganisms, 9(6):.

Christensenella minuta are human gut dwelling bacteria that have been proposed as key members of the gut microbiome, regulating energy balance and adiposity of their host. We formerly identified that a novel strain of C. minuta (strain DSM33407) boosted microbiota diversity and stimulated deconjugation of the primary bile acid taurocholic acid in human samples. However, there is no description of a bile salt hydrolase (BSH) protein carried in the genome of C. minuta. Here, we identified and cloned a protein from C. minuta's genome that carries a potent BSH activity, which preferentially deconjugates glycine-conjugated bile acids. We then retrieved 14,319 putative BSH sequences from the NCBI database and filtered them using the UHGP database to collect a total of 6701 sequences that were used to build the most comprehensive phylogenetic tree of BSH-related enzymes identified in the human microbiome so far. This phylogenetic tree revealed that C. minuta's BSH amino acid sequence clusters away from others with a threshold of 70% identity. This is therefore the first description of C. minuta's BSH protein, which may be involved in its unique role within the human gut microbial ecosystem.

RevDate: 2021-07-11
CmpDate: 2021-07-08

Rebelo JS, Domingues CPF, Dionisio F, et al (2021)

COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics.

International journal of molecular sciences, 22(13):.

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal-Wallis and Dunn's pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.

RevDate: 2021-07-02

Woods DF, Flynn S, Caparrós-Martín JA, et al (2021)

Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung.

Antibiotics (Basel, Switzerland), 10(7): pii:antibiotics10070766.

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation-pathogen-host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.

RevDate: 2021-07-05

Yan R, Andrew L, Marlow E, et al (2021)

Dietary Fibre Intervention for Gut Microbiota, Sleep, and Mental Health in Adults with Irritable Bowel Syndrome: A Scoping Review.

Nutrients, 13(7): pii:nu13072159.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting 4-5% of the global population. This disorder is associated with gut microbiota, diet, sleep, and mental health. This scoping review therefore aims to map existing research that has administrated fibre-related dietary intervention to IBS individuals and reported outcomes on at least two of the three following themes: gut microbiota, sleep, and mental health. Five digital databases were searched to identify and select papers as per the inclusion and exclusion criteria. Five articles were included in the assessment, where none reported on all three themes or the combination of gut microbiota and sleep. Two studies identified alterations in gut microbiota and mental health with fibre supplementation. The other three studies reported on mental health and sleep outcomes using subjective questionnaires. IBS-related research lacks system biology-type studies targeting gut microbiota, sleep, and mental health in patients undergoing diet intervention. Further IBS research is required to explore how human gut microbiota functions (such as short-chain fatty acids) in sleep and mental health, following the implementation of dietary pattern alteration or component supplementation. Additionally, the application of objective sleep assessments is required in order to detect sleep change with more accuracy and less bias.

RevDate: 2021-07-08
CmpDate: 2021-07-08

Dereschuk K, Apostol L, Ranjan I, et al (2021)

Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis.

Cells, 10(6):.

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

RevDate: 2021-07-12
CmpDate: 2021-07-12

Bacci G, Mengoni A, Emiliani G, et al (2021)

Defining the resilience of the human salivary microbiota by a 520-day longitudinal study in a confined environment: the Mars500 mission.

Microbiome, 9(1):152.

BACKGROUND: The human microbiota plays several roles in health and disease but is often difficult to determine which part is in intimate relationships with the host vs. the occasional presence. During the Mars500 mission, six crewmembers lived completely isolated from the outer world for 520 days following standardized diet regimes. The mission constitutes the first spaceflight simulation to Mars and was a unique experiment to determine, in a longitudinal study design, the composition and importance of the resident vs. a more variable microbiota-the fraction of the human microbiota that changes in time and according to environmental conditions-in humans.

METHODS: Here, we report the characterization of the salivary microbiota from 88 samples taken during and after Mars500 mission for a total of 720 days. Amplicon sequencing of the V3-V4 regions of 16S rRNA gene was performed, and results were analyzed monitoring the diversity of the microbiota while evaluating the effect of the three main variables present in the experimental system: time, diet, and individuality of each subject.

RESULTS: Results showed statistically significant effects for either time, diet, and individuality of each subject. The main contribution came from the individuality of each subject, emphasizing salivary microbiota-personalized features, and an individual-based resilience of the microbiota.

CONCLUSIONS: The uniqueness of Mars500 mission, allowed to dampen the effect of environmental variables on salivary microbiota, highlighting its pronounced personalization even after sharing the same physical space for more than a year. Video abstract.

RevDate: 2021-06-29

Seegers JFML, Gül IS, Hofkens S, et al (2021)

Toxicological safety evaluation of live Anaerobutyricum soehngenii strain CH106.

Journal of applied toxicology : JAT [Epub ahead of print].

The gut commensal Anaerobutyricum soehngenii is an anaerobe that can produce both propionate and butyrate, metabolites that have been shown to have a positive effect on gut and overall health. Murine and human dose finding studies have shown that oral intake of A. soehngenii has a positive influence on peripheral insulin resistance, thereby reducing the risk of type 2 diabetes. A recent human intervention provided support for the mode of action of A. soehngenii as it affected gene expression in the duodenum, stimulated the secretion of GLP-1 and improved insulin sensitivity. For these reasons A. soehngenii has been proposed as a food ingredient. Before introducing this bacterium to the food chain, however, it must be established that oral intake of live A. soehngenii bacteria does not pose any health risk. As part of the safety analysis of A. soehngenii strain CH106, we performed genotoxicity assays to determine its mutagenic potential (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day subchronic toxicity study in rats to determine overall toxicity potential. The results of both genotoxicity studies were negative, showing no genotoxic effects. For the 90-day subchronic toxicity study, no adverse events were registered that could be attributed to the feeding with A. soehngenii strain CH106. Even at the highest dose, which exceeds the expected daily human intake more than 100-fold, no adverse events were observed. These result support the conclusion that the use of A. soehngenii strain CH106 as a food ingredient is safe.

RevDate: 2021-06-29

Jacobson D, Moore K, Gunderson C, et al (2021)

Shifts in gut and vaginal microbiomes are associated with cancer recurrence time in women with ovarian cancer.

PeerJ, 9:e11574.

Many studies investigating the human microbiome-cancer interface have focused on the gut microbiome and gastrointestinal cancers. Outside of human papillomavirus driving cervical cancer, little is known about the relationship between the vaginal microbiome and other gynecological cancers, such as ovarian cancer. In this retrospective study, we investigated the relationship between ovarian cancer, platinum-free interval (PFI) length, and vaginal and gut microbiomes. We observed that Lactobacillus-dominated vaginal communities were less common in women with ovarian cancer, as compared to existing datasets of similarly aged women without cancer. Primary platinum-resistance (PPR) disease is strongly associated with survivability under one year, and we found over one-third of patients with PPR (PFI < 6 months, n = 17) to have a vaginal microbiome dominated by Escherichia (>20% relative abundance), while only one platinum super-sensitive (PFI > 24 months, n = 23) patient had an Escherichia-dominated microbiome. Additionally, L. iners was associated with little, or no, gross residual disease, while other Lactobacillus species were dominant in women with >1 cm gross residual disease. In the gut microbiome, we found patients with PPR disease to have lower phylogenetic diversity than platinum-sensitive patients. The trends we observe in women with ovarian cancer and PPR disease, such as the absence of Lactobacillus and presence of Escherichia in the vaginal microbiome as well as low gut microbiome phylogenetic diversity have all been linked to other diseases and/or pro-inflammatory states, including bacterial vaginosis and autoimmune disorders. Future prospective studies are necessary to explore the translational potential and underlying mechanisms driving these associations.

RevDate: 2021-07-01
CmpDate: 2021-06-30

Berry ASF, Pierdon MK, Misic AM, et al (2021)

Remodeling of the maternal gut microbiome during pregnancy is shaped by parity.

Microbiome, 9(1):146.

BACKGROUND: The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies-referred to as maternal parity-as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans.

RESULTS: Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring "quadrads"-each consisting of one mother sow and three piglets-linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth.

CONCLUSIONS: Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants. Video abstract.

RevDate: 2021-06-25

Djemai K, Drancourt M, M Tidjani Alou (2021)

Bacteria and Methanogens in the Human Microbiome: a Review of Syntrophic Interactions.

Microbial ecology [Epub ahead of print].

Methanogens are microorganisms belonging to the Archaea domain and represent the primary source of biotic methane. Methanogens encode a series of enzymes which can convert secondary substrates into methane following three major methanogenesis pathways. Initially recognized as environmental microorganisms, methanogens have more recently been acknowledged as host-associated microorganisms after their detection and initial isolation in ruminants in the 1950s. Methanogens have also been co-detected with bacteria in various pathological situations, bringing their role as pathogens into question. Here, we review reported associations between methanogens and bacteria in physiological and pathological situations in order to understand the metabolic interactions explaining these associations. To do so, we describe the origin of the metabolites used for methanogenesis and highlight the central role of methanogens in the syntrophic process during carbon cycling. We then focus on the metabolic abilities of co-detected bacterial species described in the literature and infer from their genomes the probable mechanisms of their association with methanogens. The syntrophic interactions between bacteria and methanogens are paramount to gut homeostasis. Therefore, any dysbiosis affecting methanogens might impact human health. Thus, the monitoring of methanogens may be used as a bio-indicator of dysbiosis. Moreover, new therapeutic approaches can be developed based on their administration as probiotics. We thus insist on the importance of investigating methanogens in clinical microbiology.

RevDate: 2021-06-27

Zozaya-Valdés E, Wong SQ, Raleigh J, et al (2021)

Detection of cell-free microbial DNA using a contaminant-controlled analysis framework.

Genome biology, 22(1):187.

BACKGROUND: The human microbiome plays an important role in cancer. Accumulating evidence indicates that commensal microbiome-derived DNA may be represented in minute quantities in the cell-free DNA of human blood and could possibly be harnessed as a new cancer biomarker. However, there has been limited use of rigorous experimental controls to account for contamination, which invariably affects low-biomass microbiome studies.

RESULTS: We apply a combination of 16S-rRNA-gene sequencing and droplet digital PCR to determine if the specific detection of cell-free microbial DNA (cfmDNA) is possible in metastatic melanoma patients. Compared to matched stool and saliva samples, the absolute concentration of cfmDNA is low but significantly above the levels detected from negative controls. The microbial community of plasma is strongly influenced by laboratory and reagent contaminants introduced during the DNA extraction and sequencing processes. Through the application of an in silico decontamination strategy including the filtering of amplicon sequence variants (ASVs) with batch dependent abundances and those with a higher prevalence in negative controls, we identify known gut commensal bacteria, such as Faecalibacterium, Bacteroides and Ruminococcus, and also other uncharacterised ASVs. We analyse additional plasma samples, highlighting the potential of this framework to identify differences in cfmDNA between healthy and cancer patients.

CONCLUSIONS: Together, these observations indicate that plasma can harbour a low yet detectable level of cfmDNA. The results highlight the importance of accounting for contamination and provide an analytical decontamination framework to allow the accurate detection of cfmDNA for future biomarker studies in cancer and other diseases.

RevDate: 2021-07-08
CmpDate: 2021-07-02

Yamamoto S, Saito M, Tamura A, et al (2021)

The human microbiome and COVID-19: A systematic review.

PloS one, 16(6):e0253293.

BACKGROUND: Human microbiotas are communities of microorganisms living in symbiosis with humans. They play an important role in the host immune response to respiratory viral infection. However, evidence on the human microbiome and coronavirus disease (COVID-19) relationship is insufficient. The aim of this systematic literature review was to evaluate existing evidence on the association between the microbiome and COVID-19 in humans and summarize these data in the pandemic era.

METHODS: We conducted a systematic literature review on the association between the microbiome and COVID-19 in humans by searching PubMed, Embase, and the Cochrane Library, CINAHL, and Web of Science databases for articles in English published up to October 31, 2020. The results were analyzed qualitatively. This study is registered with PROSPERO (CRD42020195982).

RESULTS: Of the 543 articles identified by searching databases, 16 in line with the research objectives were eligible for qualitative review: eight sampled the microbiome using stool, four using nasopharyngeal or throat swab, three using bronchoalveolar lavage fluid, and one using lung tissue. Fecal microbiome dysbiosis and increased opportunistic pathogens were reported in COVID-19 patients. Several studies suggested the dysbiosis in the lung microbiome of COVID-19 patients with an abundance of opportunistic pathogens using lower respiratory tract samples. The association between COVID-19 severity and the human microbiome remains uncertain.

CONCLUSION: The human fecal and respiratory tract microbiome changed in COVID-19 patients with opportunistic pathogen abundance. Further research to elucidate the effect of alternation of the human microbiome in disease pathogenesis is warranted.

RevDate: 2021-07-08
CmpDate: 2021-07-08

Wagner J, Kancherla J, Braccia D, et al (2020)

Interactive exploratory data analysis of Integrative Human Microbiome Project data using Metaviz.

F1000Research, 9:601.

The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In this work we describe infrastructure that integrates Metaviz, an interactive microbiome data analysis and visualization tool, with the iHMP Data Coordination Center web portal and the HMP2Data R/Bioconductor package. We describe integrative statistical and visual analyses of two datasets from iHMP using Metaviz along with the metagenomeSeq R/Bioconductor package for statistical analysis of differential abundance analysis. These use cases demonstrate the utility of a combined approach to access and analyze data from this resource.

RevDate: 2021-06-23
CmpDate: 2021-06-23

Koval TV, Chopey IV, Hechko MM, et al (2021)


Wiadomosci lekarskie (Warsaw, Poland : 1960), 74(4):1007-1010.

OBJECTIVE: The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota.

PATIENTS AND METHODS: Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed.

CONCLUSION: Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.

RevDate: 2021-06-21

Adler CJ, Cao KL, Hughes T, et al (2021)

How does the early life environment influence the oral microbiome and determine oral health outcomes in childhood?.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

The first 1000 days of life, from conception to 2 years, are a critical window for the influence of environmental exposures on the assembly of the oral microbiome, which is the precursor to dental caries (decay), one of the most prevalent microbially induced disorders worldwide. While it is known that the human microbiome is susceptible to environmental exposures, there is limited understanding of the impact of prenatal and early childhood exposures on the oral microbiome trajectory and oral health. A barrier has been the lack of technology to directly measure the foetal "exposome", which includes nutritional and toxic exposures crossing the placenta. Another barrier has been the lack of statistical methods to account for the high dimensional data generated by-omic assays. Through identifying which early life exposures influence the oral microbiome and modify oral health, these findings can be translated into interventions to reduce dental decay prevalence.

RevDate: 2021-06-22

Morrison MD, Thissen JB, Karouia F, et al (2021)

Investigation of Spaceflight Induced Changes to Astronaut Microbiomes.

Frontiers in microbiology, 12:659179.

The International Space Station (ISS) is a uniquely enclosed environment that has been continuously occupied for the last two decades. Throughout its operation, protecting the health of the astronauts on-board has been a high priority. The human microbiome plays a significant role in maintaining human health, and disruptions in the microbiome have been linked to various diseases. To evaluate the effects of spaceflight on the human microbiome, body swabs and saliva samples were collected from four ISS astronauts on consecutive expeditions. Astronaut samples were analyzed using shotgun metagenomic sequencing and microarrays to characterize the microbial biodiversity before, during, and after the astronauts' time onboard the ISS. Samples were evaluated at an individual and population level to identify changes in microbial diversity and abundance. No significant changes in the number or relative abundance of taxa were observed between collection time points when samples from all four astronauts were analyzed together. When the astronauts' saliva samples were analyzed individually, the saliva samples of some astronauts showed significant changes in the relative abundance of taxa during and after spaceflight. The relative abundance of Prevotella in saliva samples increased during two astronauts' time onboard the ISS while the relative abundance of other commensal taxa such as Neisseria, Rothia, and Haemophilus decreased. The abundance of some antimicrobial resistance genes within the saliva samples also showed significant changes. Most notably, elfamycin resistance gene significantly increased in all four astronauts post-flight and a CfxA6 beta-lactam marker significantly increased during spaceflight but returned to normal levels post-flight. The combination of both shotgun metagenomic sequencing and microarrays showed the benefit of both technologies in monitoring microbes on board the ISS. There were some changes in each astronaut's microbiome during spaceflight, but these changes were not universal for all four astronauts. Two antimicrobial resistance gene markers did show a significant change in abundance in the saliva samples of all four astronauts across their collection times. These results provide insight for future ISS microbial monitoring studies and targets for antimicrobial resistance screenings.

RevDate: 2021-07-05
CmpDate: 2021-07-05

de Cena JA, Zhang J, Deng D, et al (2021)

Low-Abundant Microorganisms: The Human Microbiome's Dark Matter, a Scoping Review.

Frontiers in cellular and infection microbiology, 11:689197.

Research on the human microbiome has mainly been restricted to the identification of most abundant microbiota associated with health or disease. Their abundance may reflect their capacity to exploit their niche, however, metabolic functions exerted by low-abundant microrganisms can impact the dysbiotic signature of local microbial habitats. This scoping review aims to map the literature regarding the management of low-abundant microorganisms in studies investigating human microbiome samples. A systematic literature search was performed in 5 electronic databases, as well as grey literature. We selected clinical microbiome studies targeting human participants of any age, from any body site. We also included studies with secondary data which originated from human biofilm samples. All of the papers used next-generation sequencing (NGS) techniques in their methodology. A total of 826 manuscripts were retrieved, of which 42 were included in this review and 22 reported low-abundant bacteria (LB) in samples taken from 7 body sites (breast, gut, oral cavity, skin, stomach, upper respiratory tract (URT), and vagina). Four studies reported microbes at abundance levels between 5 and 20%, 8 studies reported between 1 and 5%, and 18 studies reported below 1%. Fifteen papers mentioned fungi and/or archaea, and from those only 4 (fungi) and 2 (archaea) produced data regarding the abundance of these domains. While most studies were directed towards describing the taxonomy, diversity and abundance of the highly abundant species, low-abundant species have largely been overlooked. Indeed, most studies select a cut-off value at <1% for low-abundant organisms to be excluded in their analyses. This practice may compromise the true diversity and influence of all members of the human microbiota. Despite their low abundance and signature in biofilms, they may generate important markers contributing to dysbiosis, in a sort of 'butterfly effect'. A detailed snapshot of the physiological, biological mechanisms at play, including virulence determinants in the context of a dysbiotic community, may help better understand the health-disease transition.

RevDate: 2021-06-19

Ma ZS (2021)

Spatial heterogeneity analysis of the human virome with Taylor's power law.

Computational and structural biotechnology journal, 19:2921-2927.

Spatial heterogeneity is a fundamental characteristic of organisms from viruses to humans. Measuring heterogeneity is challenging, especially for naked-eye invisible viruses, but of obvious importance. For example, spatial heterogeneity of virus distribution may strongly influence infection spreading and outbreaks in the case of pathogenic viruses; the spatial distribution (i.e., the inter-subject heterogeneity) of commensal viruses within/on our bodies can influence the competition, coexistence, and dispersal of viruses within or between our bodies. Taylor's power law (TPL) was first discovered in the 1960s to describe the spatial distributions of plant and/or animal populations, and since then it has been verified by numerous experimental and theoretical studies. Recently, TPL has been extended from population to community level and applied to bacterial communities. Here we report the first comprehensive testing of the TPL fitted to human virome datasets. It was found that the human virome follows the TPL as bacterial communities do. Furthermore, the TPL heterogeneity scaling parameter of human virome is virtually the same as that of the human bacterial microbiome (1.916 vs. 1.926). We postulate that the extreme closeness of human viruses and bacteria in heterogeneity scaling coefficients could be attributed to the fact that most of the viruses that were annotated in this study actually belong to bacteriophages (86% viral OTUs) that "piggyback" on their bacterial hosts, and their distributions are likely host-dependent. The scaling parameter, which measures the inter-subject heterogeneity changes, should be an innate property of human microbiomes including both bacteria and viruses. It is similar to the acceleration coefficient of the gravity (g = 9.8) as specified by Newton's law, which is invariant on the earth. Nevertheless, we caution that our postulation is contingent on an implicit assumption that the proportion of bacteriophages to total virome may not change significantly when more virus species can be identified in future.

RevDate: 2021-07-06

Nuzzo A, Van Horn S, Traini C, et al (2021)

Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944).

BMC microbiology, 21(1):181.

BACKGROUND: With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov : NCT03568942).

RESULTS: Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa.

CONCLUSION: Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery.

TRIAL REGISTRATION: NCT03568942 . Registered 26 June 2018.

RevDate: 2021-06-28

Salmenkari H, Korpela R, H Vapaatalo (2021)

Renin-angiotensin system in intestinal inflammation-Angiotensin inhibitors to treat inflammatory bowel diseases?.

Basic & clinical pharmacology & toxicology [Epub ahead of print].

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin-angiotensin system (RAS), besides being antihypertensive, also possess anti-inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.

RevDate: 2021-06-25

Priskorn L, Tøttenborg SS, Almstrup K, et al (2021)

RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity.

Andrology [Epub ahead of print].

BACKGROUND: Infertility affects 15%-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth.

OBJECTIVES: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?

MATERIAL AND METHODS: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.

RevDate: 2021-06-24

Owens JA, Saeedi BJ, Naudin CR, et al (2021)

Lactobacillus rhamnosus GG Orchestrates an Anti-tumor Immune Response.

Cellular and molecular gastroenterology and hepatology pii:S2352-345X(21)00115-6 [Epub ahead of print].

BACKGROUND & AIMS: In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy.

METHODS: The gut microbiome has been described as a master modulator of immune responses. We administered the human commensal, Lactobacillus rhamnosus GG (LGG), to mice and characterized the changes in the gut immune landscape. Because the presence of lactobacilli in the gut microbiome has been linked with decreased tumor burden and antitumor immune responses, we also supplemented a genetic and a chemical model of murine intestinal cancer with LGG. For clinical relevance, we therapeutically administered LGG after tumors had formed. We also tested for the requirement of CD8 T cells in LGG-mediated modulation of gut tumor burden.

RESULTS: We detected increased colonic CD8 T-cell responses specifically in LGG-supplemented mice. The CD8 T-cell induction was dependent on dendritic cell activation mediated via Toll-like receptor-2, thereby describing a novel mechanism in which a member of the human microbiome induces an intestinal CD8 T-cell response. We also show that LGG decreased tumor burden in the murine gut cancer models by a CD8 T-cell-dependent manner.

CONCLUSIONS: These data support the potential use of LGG to augment antitumor immune responses in colorectal cancer patients and ultimately for increasing the breadth and efficacy of immunotherapy.

RevDate: 2021-06-10

Le Roy T, Moens de Hase E, Van Hul M, et al (2021)

Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice.

Gut pii:gutjnl-2020-323778 [Epub ahead of print].

OBJECTIVE: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.

DESIGN: We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115T on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice.

RESULTS: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115T, but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115T administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition.

CONCLUSIONS: These results suggest that D. welbionis J115T directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.

RevDate: 2021-06-13

Flachs A, JD Orkin (2021)

On pickles: biological and sociocultural links between fermented foods and the human gut microbiome.

Journal of ethnobiology and ethnomedicine, 17(1):39.

BACKGROUND: The composition of the human microbiome varies considerably in diversity and density across communities as a function of the foods we eat and the places we live. While all foods contain microbes, humans directly shape this microbial ecology through fermentation. Fermented foods are produced from microbial reactions that depend on local environmental conditions, fermentation practices, and the manner in which foods are prepared and consumed. These interactions are of special interest to ethnobiologists because they link investigations of how people shape and know the world around them to local knowledge, food traditions, local flora, and microbial taxa.

METHODS: In this manuscript, we report on data collected at a fermentation revivalist workshop in Tennessee. To ask how fermentation traditions are learned and influence macro and micro ecologies, we conducted interviews with eleven people and participated in a four-day craft fermentation workshop. We also collected 46 fermented food products and 46 stool samples from workshop participants eating those fermented foods.

RESULTS: We identified ten major themes comprised of 29 sub-themes drawn from 326 marked codes in the transcripts. In combination, this analysis allowed us to summarize key experiences with fermentation, particularly those related to a sense of authenticity, place, health, and the discovery of tactile work. From the 605 amplicon sequence variants (ASVs) shared between food and fecal samples, we identified 25 candidate ASVs that are suspected to have been transmitted from fermented food samples to the gut microbiomes of the workshop participants. Our results indicate that many of the foods prepared and consumed during the workshop were rich sources of probiotic microbes.

CONCLUSIONS: By combining these qualitative social and quantitative microbiological data, we suggest that variation in culturally informed fermentation practices introduces variation in bacterial flora even among very similar foods, and that these food products can influence gut microbial ecology.

RevDate: 2021-06-08

Atzler M, Westhofen T, Tamalunas A, et al (2021)

[The role of the microbiome in urological diseases].

Aktuelle Urologie [Epub ahead of print].

The use of modern molecular technologies in the last decade has given us new insights into the complex interactions of the human microbiome in health and in the pathogenesis of diseases. Among other things, the sterility concept of the urinary tract has been discarded and the goal is now to identify the different microbial signatures associated with various diseases. Dysbalances of the microbiome are increasingly suspected of causing negative effects on various malignant and benign diseases. Recently, such associations have also been shown for prostate carcinoma, renal cell carcinoma and urinary bladder carcinoma. This may lead to the discovery of new potential biomarkers for the diagnosis and as a therapeutic target of the diseases mentioned. For the diagnosis of some benign diseases such as interstitial cystitis, urge incontinence and chronic prostatitis or chronic pelvic pain syndrome, microbial involvement was previously considered an exclusion criterion. However, current studies show that the individual patient's microbiome can have an influence on the development and severity of the respective disease.

RevDate: 2021-06-11
CmpDate: 2021-06-09

Weissman JL, Dogra S, Javadi K, et al (2021)

Exploring the functional composition of the human microbiome using a hand-curated microbial trait database.

BMC bioinformatics, 22(1):306.

BACKGROUND: Even when microbial communities vary wildly in their taxonomic composition, their functional composition is often surprisingly stable. This suggests that a functional perspective could provide much deeper insight into the principles governing microbiome assembly. Much work to date analyzing the functional composition of microbial communities, however, relies heavily on inference from genomic features. Unfortunately, output from these methods can be hard to interpret and often suffers from relatively high error rates.

RESULTS: We built and analyzed a domain-specific microbial trait database from known microbe-trait pairs recorded in the literature to better understand the functional composition of the human microbiome. Using a combination of phylogentically conscious machine learning tools and a network science approach, we were able to link particular traits to areas of the human body, discover traits that determine the range of body areas a microbe can inhabit, and uncover drivers of metabolic breadth.

CONCLUSIONS: Domain-specific trait databases are an effective compromise between noisy methods to infer complex traits from genomic data and exhaustive, expensive attempts at database curation from the literature that do not focus on any one subset of taxa. They provide an accurate account of microbial traits and, by limiting the number of taxa considered, are feasible to build within a reasonable time-frame. We present a database specific for the human microbiome, in the hopes that this will prove useful for research into the functional composition of human-associated microbial communities.

RevDate: 2021-06-09

Zhang H, Chen J, Li Z, et al (2021)

Testing for mediation effect with application to human microbiome data.

Statistics in biosciences, 13(2):313-328.

Mediation analysis has been commonly used to study the effect of an exposure on an outcome through a mediator. In this paper, we are interested in exploring the mediation mechanism of microbiome, whose special features make the analysis challenging. We consider the isometric logratio transformation of the relative abundance as the mediator variable. Then, we present a de-biased Lasso estimate for the mediator of interest and derive its standard error estimator, which can be used to develop a test procedure for the interested mediation effect. Extensive simulation studies are conducted to assess the performance of our method. We apply the proposed approach to test the mediation effect of human gut microbiome between the dietary fiber intake and body mass index.

RevDate: 2021-06-25

Visick KL, Stabb EV, EG Ruby (2021)

A lasting symbiosis: how Vibrio fischeri finds a squid partner and persists within its natural host.

Nature reviews. Microbiology [Epub ahead of print].

As our understanding of the human microbiome progresses, so does the need for natural experimental animal models that promote a mechanistic understanding of beneficial microorganism-host interactions. Years of research into the exclusive symbiosis between the Hawaiian bobtail squid, Euprymna scolopes, and the bioluminescent bacterium Vibrio fischeri have permitted a detailed understanding of those bacterial genes underlying signal exchange and rhythmic activities that result in a persistent, beneficial association, as well as glimpses into the evolution of symbiotic competence. Migrating from the ambient seawater to regions deep inside the light-emitting organ of the squid, V. fischeri experiences, recognizes and adjusts to the changing environmental conditions. Here, we review key advances over the past 15 years that are deepening our understanding of these events.

RevDate: 2021-06-24
CmpDate: 2021-06-24

Barquero-Orias D, Muñoz Moreno-Arrones O, S Vañó-Galván (2021)

Alopecia and the Microbiome: A Future Therapeutic Target?.

Actas dermo-sifiliograficas, 112(6):495-502.

The human microbiome includes viruses, bacteria, and fungi. There is evidence that in addition to microbiome variation in different areas of the body or according to ethnicity and sex, the microbiome specific to the scalp is conditioned by such factors as humidity, protection from UV light, and pH. Although little information has yet been published about the microbiome of hair follicles and its role in the pathogenesis of diseases, interest in this area of research is emerging. Studies have shown that components of the follicular microbiome influence such disorders as androgenetic alopecia and alopecia areata. A current hypothesis is that interventions that target the microbiome may lead to innovative therapies for many diseases.

RevDate: 2021-06-05

Hollingsworth BA, Cassatt DR, DiCarlo AL, et al (2021)

Acute Radiation Syndrome and the Microbiome: Impact and Review.

Frontiers in pharmacology, 12:643283.

Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.

RevDate: 2021-06-04

Patpatia S, Yilmaz O, Ylänne M, et al (2021)

Isolation and Genomic Analysis of the Phage vB_PaeP_fHoPae04 Infecting Pseudomonas aeruginosa.

Microbiology resource announcements, 10(22):e0007621.

Here, we report the genomic sequence of Pseudomonas aeruginosa phage vB_PaeP_fHoPae04, isolated from hospital wastewater in Helsinki, Finland. The phage genome is 45,491 bp long, has a G+C content of 52.2%, and contains 70 protein-coding genes and 3 tRNA genes.

RevDate: 2021-06-02

Hanssen NMJ, de Vos WM, M Nieuwdorp (2021)

Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?.

Cell metabolism, 33(6):1098-1110.

Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.

RevDate: 2021-06-29

Sanders DJ, Inniss S, Sebepos-Rogers G, et al (2021)

The role of the microbiome in gastrointestinal inflammation.

Bioscience reports, 41(6):.

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.

RevDate: 2021-07-10

Murovec B, Deutsch L, B Stres (2021)

General Unified Microbiome Profiling Pipeline (GUMPP) for Large Scale, Streamlined and Reproducible Analysis of Bacterial 16S rRNA Data to Predicted Microbial Metagenomes, Enzymatic Reactions and Metabolic Pathways.

Metabolites, 11(6):.

General Unified Microbiome Profiling Pipeline (GUMPP) was developed for large scale, streamlined and reproducible analysis of bacterial 16S rRNA data and prediction of microbial metagenomes, enzymatic reactions and metabolic pathways from amplicon data. GUMPP workflow introduces reproducible data analyses at each of the three levels of resolution (genus; operational taxonomic units (OTUs); amplicon sequence variants (ASVs)). The ability to support reproducible analyses enables production of datasets that ultimately identify the biochemical pathways characteristic of disease pathology. These datasets coupled to biostatistics and mathematical approaches of machine learning can play a significant role in extraction of truly significant and meaningful information from a wide set of 16S rRNA datasets. The adoption of GUMPP in the gut-microbiota related research enables focusing on the generation of novel biomarkers that can lead to the development of mechanistic hypotheses applicable to the development of novel therapies in personalized medicine.

RevDate: 2021-07-11
CmpDate: 2021-06-10

Virtanen J, Uusitalo R, Korhonen EM, et al (2021)

Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7, and B 1.351 Isolates in Microneutralization Assays.

Viruses, 13(6):.

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.

RevDate: 2021-07-10

Onali T, Kivimäki A, Mauramo M, et al (2021)

Anticancer Effects of Lingonberry and Bilberry on Digestive Tract Cancers.

Antioxidants (Basel, Switzerland), 10(6):.

Wild berries are part of traditional Nordic diets and are a rich source of phytochemicals, such as polyphenols. Various berry treatments have shown to interfere with cancer progression in vitro and in vivo. Here, we systematically reviewed the anticancer effects of two Nordic wild berries of the Vaccinium genus, lingonberry (Vaccinium vitis-idaea) and bilberry (Vaccinium myrtillus), on digestive tract cancers. The review was conducted according to the PRISMA 2020 guidelines. Searches included four databases: PubMed, Scopus, Web of Science, and CAB abstracts. Publications not written in English, case-reports, reviews, and conference abstracts were excluded. Moreover, studies with only indirect markers of cancer risk or studies with single compounds not derived from lingonberry or bilberry were not included. Meta-analysis was not performed. The majority (21/26) of studies investigated bilberry and colorectal cancer. Experimental studies on colorectal cancer indicated that bilberry inhibited intestinal tumor formation and cancer cell growth. One uncontrolled pilot human study supported the inhibitory potential of bilberry on colorectal cancer cell proliferation. Data from all 10 lingonberry studies suggests potent inhibition of cancer cell growth and tumor formation. In conclusion, in vitro and animal models support the antiproliferative and antitumor effects of various bilberry and lingonberry preparations on digestive tract cancers.

RevDate: 2021-06-15

Nagy KK, Skurnik M, BG Vértessy (2021)

Viruses with U-DNA: New Avenues for Biotechnology.

Viruses, 13(5):.

Deoxyuridine in DNA has recently been in the focus of research due to its intriguing roles in several physiological and pathophysiological situations. Although not an orthodox DNA base, uracil may appear in DNA via either cytosine deamination or thymine-replacing incorporations. Since these alterations may induce mutation or may perturb DNA-protein interactions, free living organisms from bacteria to human contain several pathways to counteract uracilation. These efficient and highly specific repair routes uracil-directed excision repair initiated by representative of uracil-DNA glycosylase families. Interestingly, some bacteriophages exist with thymine-lacking uracil-DNA genome. A detailed understanding of the strategy by which such phages can replicate in bacteria where an efficient repair pathway functions for uracil-excision from DNA is expected to reveal novel inhibitors that can also be used for biotechnological applications. Here, we also review the several potential biotechnological applications already implemented based on inhibitors of uracil-excision repair, such as Crispr-base-editing and detection of nascent uracil distribution pattern in complex genomes.

RevDate: 2021-06-15

Ndika J, Karisola P, Kinaret P, et al (2021)

Profiling Non-Coding RNA Changes Associated with 16 Different Engineered Nanomaterials in a Mouse Airway Exposure Model.

Cells, 10(5):.

Perturbations in cellular molecular events and their associated biological processes provide opportunities for hazard assessment based on toxicogenomic profiling. Long non-coding RNAs (lncRNAs) are transcribed from DNA but are typically not translated into full-length proteins. Via epigenetic regulation, they play important roles in organismal response to environmental stress. The effects of nanoparticles on this important part of the epigenome are understudied. In this study, we investigated changes in lncRNA associated with hazardous inhalatory exposure of mice to 16 engineered nanomaterials (ENM)-4 ENM (copper oxide, multi-walled carbon nanotubes, spherical titanium dioxide, and rod-like titanium dioxide particles) with 4 different surface chemistries (pristine, COOH, NH2, and PEG). Mice were exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by cytological analyses and transcriptomic characterization of whole lung tissues. The number of significantly altered non-coding RNA transcripts, suggestive of their degrees of toxicity, was different for each ENM type. Particle surface chemistry and shape also had varying effects on lncRNA expression. NH2 and PEG caused the strongest and weakest responses, respectively. Via correlational analyses to mRNA expression from the same samples, we could deduce that significantly altered lncRNAs are potential regulators of genes involved in mitotic cell division and DNA damage response. This study sheds more light on epigenetic mechanisms of ENM toxicity and also emphasizes the importance of the lncRNA superfamily as toxicogenomic markers of adverse ENM exposure.

RevDate: 2021-06-12

Maras B, Maggiore A, Mignogna G, et al (2021)

Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.

PloS one, 16(6):e0252555.

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.

RevDate: 2021-06-30

Zhou J, Yu X, Liu J, et al (2021)

VB12Path for Accurate Metagenomic Profiling of Microbially Driven Cobalamin Synthesis Pathways.

mSystems, 6(3):e0049721.

Cobalamin (vitamin B12; VB12) is an indispensable nutrient for all living entities in the Earth's biosphere and plays a vital role in both natural and host environments. Currently in the metagenomic era, gene families of interest are extracted and analyzed based on functional profiles by searching shotgun metagenomes against public databases. However, critical issues exist in applying public databases for specific processes such as VB12 biosynthesis pathways. We developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 biosynthesis gene families of microbial communities in complex environments. VB12Path contains a total of 60 VB12 synthesis gene families, 287,731 sequences, and 21,154 homology groups, and it aims to provide accurate functional and taxonomic profiles of VB12 synthesis pathways for shotgun metagenomes and minimize false-positive assignments. VB12Path was applied to characterize cobalamin biosynthesis gene families in human intestines and marine environments. The results demonstrated that ocean and human intestine had dramatically different VB12 synthesis processes and that gene families belonging to salvage and remodeling pathway dominated human intestine but were lowest in the ocean ecosystem. VB12Path is expected to be a useful tool to study cobalamin biosynthesis processes via shotgun metagenome sequencing in both environmental and human microbiome research. IMPORTANCE Vitamin B12 (VB12) is an indispensable nutrient for all living entities in the world but can only be synthesized by a small subset of prokaryotes. Therefore, this small subset of prokaryotes controls ecosystem stability and host health to some extent. However, critical accuracy and comprehensiveness issues exist in applying public databases to profile VB12 synthetic gene families and taxonomic groups in complex metagenomes. In this study, we developed a curated functional gene database termed VB12Path for accurate metagenomic profiling of VB12 communities in complex environments. VB12Path is expected to serve as a valuable tool to uncover the hidden microbial communities producing this precious nutrient on Earth.

RevDate: 2021-06-01

Lomsadze A, Bonny C, Strozzi F, et al (2021)

GeneMark-HM: improving gene prediction in DNA sequences of human microbiome.

NAR genomics and bioinformatics, 3(2):lqab047.

Computational reconstruction of nearly complete genomes from metagenomic reads may identify thousands of new uncultured candidate bacterial species. We have shown that reconstructed prokaryotic genomes along with genomes of sequenced microbial isolates can be used to support more accurate gene prediction in novel metagenomic sequences. We have proposed an approach that used three types of gene prediction algorithms and found for all contigs in a metagenome nearly optimal models of protein-coding regions either in libraries of pre-computed models or constructed de novo. The model selection process and gene annotation were done by the new GeneMark-HM pipeline. We have created a database of the species level pan-genomes for the human microbiome. To create a library of models representing each pan-genome we used a self-training algorithm GeneMarkS-2. Genes initially predicted in each contig served as queries for a fast similarity search through the pan-genome database. The best matches led to selection of the model for gene prediction. Contigs not assigned to pan-genomes were analyzed by crude, but still accurate models designed for sequences with particular GC compositions. Tests of GeneMark-HM on simulated metagenomes demonstrated improvement in gene annotation of human metagenomic sequences in comparison with the current state-of-the-art gene prediction tools.

RevDate: 2021-06-01

Asija K, Sutter M, CA Kerfeld (2021)

A Survey of Bacterial Microcompartment Distribution in the Human Microbiome.

Frontiers in microbiology, 12:669024.

Bacterial microcompartments (BMCs) are protein-based organelles that expand the metabolic potential of many bacteria by sequestering segments of enzymatic pathways in a selectively permeable protein shell. Sixty-eight different types/subtypes of BMCs have been bioinformatically identified based on the encapsulated enzymes and shell proteins encoded in genomic loci. BMCs are found across bacterial phyla. The organisms that contain them, rather than strictly correlating with specific lineages, tend to reflect the metabolic landscape of the environmental niches they occupy. From our recent comprehensive bioinformatic survey of BMCs found in genome sequence data, we find many in members of the human microbiome. Here we survey the distribution of BMCs in the different biotopes of the human body. Given their amenability to be horizontally transferred and bioengineered they hold promise as metabolic modules that could be used to probiotically alter microbiomes or treat dysbiosis.

RevDate: 2021-05-30

Iorio A, Biazzo M, Gardini S, et al (2021)

Cross-correlation of virome-bacteriome-host-metabolome to study respiratory health.

Trends in microbiology pii:S0966-842X(21)00122-0 [Epub ahead of print].

A comprehensive understanding of the microbiome-host relationship in respiratory diseases can be elucidated by exploring the landscape of virome-bacteriome-host metabolome data through unsupervised 'multi-omics' approaches. Here, we describe how the composition and function of airway and gut virome and bacteriome may contribute to pathogen establishment and propagation in airway districts and how the virome-bacteriome communities may react to respiratory diseases. A new systems medicine approach, including the characterization of respiratory and gut microbiome, may be crucial to demonstrate the likelihood and odds of respiratory disease pathophysiology, opening new avenues to the discovery of a chain of causation for key bacteria and viruses in disease severity.

RevDate: 2021-05-29

Tett A, Pasolli E, Masetti G, et al (2021)

Prevotella diversity, niches and interactions with the human host.

Nature reviews. Microbiology [Epub ahead of print].

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.

RevDate: 2021-05-28

Andreu-Sánchez S, Chen L, Wang D, et al (2021)

A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing.

Frontiers in genetics, 12:648229.

Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK's tools as reliable variant callers for metagenomic samples.

RevDate: 2021-05-26

Langlois L, Akhtar N, Tam KC, et al (2021)

Fishing for the right probiotic: Host-microbe interactions at the interface of effective aquaculture strategies.

FEMS microbiology reviews pii:6284803 [Epub ahead of print].

Effective aquaculture management strategies are paramount to global food security. Growing demands stimulate the intensification of production and create the need for practices that are both economically viable and environmentally sustainable. Importantly, pathogenic microbes continue to be detrimental to fish growth and survival. In terms of host health, the intestinal mucosa and its associated consortium of microbes have a critical role in modulating fitness and present an attractive opportunity to promote health at this interface. In light of this, the administration of probiotic microorganisms is being considered as a means to restore and sustain health in fish. Current evidence suggests that certain probiotic strains might be able to augment immunity, enhance growth rate, and protect against infection in salmonids, the most economically important family of farmed finfish. This review affirms the relevance of host-microbe interactions in salmonids in light of emerging evidence, with an emphasis on intestinal health. In addition, the current understanding of the mode of action of probiotics in salmonid fish is discussed, along with delivery systems that can effectively carry the living microbes.

RevDate: 2021-05-28

Mansour SR, Moustafa MAA, Saad BM, et al (2021)

Impact of diet on human gut microbiome and disease risk.

New microbes and new infections, 41:100845.

The gut microbiome of humans comprises a diverse group of trillions of microorganisms including symbiotic organisms, opportunistic pathogens and commensal organisms. This microbiota plays a major role in digesting food; it also helps with absorbing and synthesizing some nutrients and releases their metabolites, which may deliver a variety of growth-promoting and growth-inhibiting factors that influence human health either directly or indirectly. The balance between microbial species, especially those responsible for the fermentation of different substrates within the microbial community, which are in the majority, depends on daily diet. Therefore, an unbalanced diet may lead to the progression and development of human diseases. These include metabolic and inflammatory disorders, cancer and depression, as well as infant health and longevity. We provide an overview of the effect of diet on the human microbiome and assess the related risk of disease development.

RevDate: 2021-06-22

Lakshmanan AP, Shatat IF, Zaidan S, et al (2021)

Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 140:111736.

Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.

RevDate: 2021-05-26

Shafaei A, Rees J, Christophersen CT, et al (2021)

Data supporting development and validation of liquid chromatography tandem mass spectrometry method for the quantitative determination of bile acids in feces.

Data in brief, 36:107091.

Measuring bile acids in feces has an important role in disease prevention, diagnosis, treatment, and can be considered a measure of health status. Therefore, the primary aim was to develop a sensitive, robust, and high throughput liquid chromatography tandem mass spectrometry method with minimal sample preparation for quantitative determination of bile acids in human feces applicable to large cohorts. Due to the chemical diversity of bile acids, their wide concentration range in feces, and the complexity of feces itself, developing a sensitive and selective analytical method for bile acids is challenging. A simple extraction method using methanol suitable for subsequent quantification by liquid chromatography tandem mass spectrometry has been reported in, "Extraction and quantitative determination of bile acids in feces" [1]. The data highlight the importance of optimization of the extraction procedure and the stability of the bile acids in feces post-extraction and prior to analysis and after several freeze-thaw cycles.

RevDate: 2021-05-26

Beauruelle C, Guilloux CA, Lamoureux C, et al (2021)

The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases.

Frontiers in medicine, 8:600879.

The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal "microgenderome" has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.

RevDate: 2021-06-10

Kinaret PAS, Ndika J, Ilves M, et al (2021)

Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways.

Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8(10):2004588.

Toxicogenomics opens novel opportunities for hazard assessment by utilizing computational methods to map molecular events and biological processes. In this study, the transcriptomic and immunopathological changes associated with airway exposure to a total of 28 engineered nanomaterials (ENM) are investigated. The ENM are selected to have different core (Ag, Au, TiO2, CuO, nanodiamond, and multiwalled carbon nanotubes) and surface chemistries (COOH, NH2, or polyethylene glycosylation (PEG)). Additionally, ENM with variations in either size (Au) or shape (TiO2) are included. Mice are exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by extensive histological/cytological analyses and transcriptomic characterization of lung tissue. The results demonstrate that transcriptomic alterations are correlated with the inflammatory cell infiltrate in the lungs. Surface modification has varying effects on the airways with amination rendering the strongest inflammatory response, while PEGylation suppresses toxicity. However, toxicological responses are also dependent on ENM core chemistry. In addition to ENM-specific transcriptional changes, a subset of 50 shared differentially expressed genes is also highlighted that cluster these ENM according to their toxicity. This study provides the largest in vivo data set currently available and as such provides valuable information to be utilized in developing predictive models for ENM toxicity.

RevDate: 2021-05-26

Rogers AE, Hu YJ, Yue Y, et al (2021)

Shiftwork, functional bowel symptoms, and the microbiome.

PeerJ, 9:e11406.

Background: There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms.

Methods: Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS.

Results: There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.

RevDate: 2021-06-25
CmpDate: 2021-06-25

Liu C, Du MX, Abuduaini R, et al (2021)

Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank.

Microbiome, 9(1):119.

BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.

RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database.

CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.

RevDate: 2021-07-13

Palombo G, Merone M, Altomare A, et al (2021)

The impact of the intestinal microbiota and the mucosal permeability on three different antibiotic drugs.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 164:105869.

BackgroundThe totality of bacteria, protozoa, viruses and fungi that lives in the human body is called microbiota. Human microbiota specifically colonizes the skin, the respiratory and urinary tract, the urogenital tract and the gastrointestinal system. This study focuses on the intestinal microbiota to explore the drug-microbiota relationship and, therefore, how the drug bioavailability changes in relation to the microbiota biodiversity to identify more personalized therapies, with the minimum risk of side effects. MethodsTo achieve this goal, we developed a new mathematical model with two compartments, the intestine and the blood, which takes into account the colonic mucosal permeability variation - measured by Ussing chamber system on human colonic mucosal biopsies - and the fecal microbiota composition, determined through microbiota 16S rRNA sequencing analysis. Both of the clinical parameters were evaluated in a group of Irritable Bowel Syndrome patients compared to a group of healthy controls. Key ResultsThe results show that plasma drug concentration increases as bacterial concentration decreases, while it decreases as intestinal length decreases too. ConclusionsThe study provides interesting data since in literature there are not yet mathematical models with these features, in which the importance of intestinal microbiota, the "forgotten organ", is considered both for the subject health state and in the nutrients and drugs metabolism.

RevDate: 2021-07-12

Pascal Andreu V, Roel-Touris J, Dodd D, et al (2021)

The gutSMASH web server: automated identification of primary metabolic gene clusters from the gut microbiota.

Nucleic acids research, 49(W1):W263-W270.

Anaerobic bacteria from the human microbiome produce a wide array of molecules at high concentrations that can directly or indirectly affect the host. The production of these molecules, mostly derived from their primary metabolism, is frequently encoded in metabolic gene clusters (MGCs). However, despite the importance of microbiome-derived primary metabolites, no tool existed to predict the gene clusters responsible for their production. For this reason, we recently introduced gutSMASH. gutSMASH can predict 41 different known pathways, including MGCs involved in bioenergetics, but also putative ones that are candidates for novel pathway discovery. To make the tool more user-friendly and accessible, we here present the gutSMASH web server, hosted at https://gutsmash.bioinformatics.nl/. The user can either input the GenBank assembly accession or upload a genome file in FASTA or GenBank format. Optionally, the user can enable additional analyses to obtain further insights into the predicted MGCs. An interactive HTML output (viewable online or downloadable for offline use) provides a user-friendly way to browse functional gene annotations and sequence comparisons with reference gene clusters as well as gene clusters predicted in other genomes. Thus, this web server provides the community with a streamlined and user-friendly interface to analyze the metabolic potential of gut microbiomes.

RevDate: 2021-05-21

Khan Mirzaei M, L Deng (2021)

New technologies for developing phage-based tools to manipulate the human microbiome.

Trends in microbiology pii:S0966-842X(21)00118-9 [Epub ahead of print].

Gut bacteria play an essential role in the human body by regulating multiple functions, producing essential metabolites, protecting against pathogen invasion, and much more. Conversely, changes in their community structure are linked to several gastrointestinal (GI) and non-GI conditions. Fortunately, these bacteria are amenable to external perturbations, but we need specific tools for their safe manipulation as nonspecific changes can cause unpredicted long-term consequences. Here, we mainly discuss recent advances in cultivation-independent technologies and argue their relevance to different key steps, that is, identifying the modulation targets and developing phage-based tools to precisely modulate gut bacteria and restore a sustainable microbiome in humans. We finally suggest multiple modulating strategies for different dysbiosis-associated diseases.

RevDate: 2021-06-28
CmpDate: 2021-06-28

Dixit K, Chaudhari D, Dhotre D, et al (2021)

Restoration of dysbiotic human gut microbiome for homeostasis.

Life sciences, 278:119622.

The human microbiome is a complex and dynamic ecosystem, and the imbalance of its microbial community structure from the normal state is termed dysbiosis. The dysbiotic gut microbiome has been proved to be related to several pathological conditions like Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Colorectal Cancer (CRC), etc., and several other extra-intestinal conditions like Type 1 & 2 diabetes, obesity, etc. The complex gut microbial ecosystem starts to build before the birth of an individual. It is known to get affected by several factors such as birth mode, individual lifestyle, dietary practices, medications, and antibiotics. A dysbiotic microbiome can potentially hamper host homeostasis due to its role in immune modulation, metabolism, nutrient synthesis, etc. Restoration of the dysbiotic gut microbiome has emerged as a promising aid and a better therapeutic approach. Several approaches have been investigated to achieve this goal, including prebiotics and probiotics, Fecal Microbiota Transplantation (FMT), extracellular vesicles, immune modulation, microbial metabolites, dietary interventions, and phages. This review discusses the various factors that influence the human microbiome with respect to their cause-effect relationship and the effect of gut microbiome compositional changes on the brain through the gut-brain axis. We also discuss the practices used globally for gut microbiome restoration purposes, along with their effectiveness.

RevDate: 2021-06-08

Liu J, Zhang X, Chen T, et al (2021)

A semiparametric model for between-subject attributes: Applications to beta-diversity of microbiome data.

Biometrics [Epub ahead of print].

The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.

RevDate: 2021-06-14
CmpDate: 2021-06-14

Tierney BT, Tan Y, Kostic AD, et al (2021)

Gene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators.

Nature communications, 12(1):2907.

We propose microbiome disease "architectures": linking >1 million microbial features (species, pathways, and genes) to 7 host phenotypes from 13 cohorts using a pipeline designed to identify associations that are robust to analytical model choice. Here, we quantify conservation and heterogeneity in microbiome-disease associations, using gene-level analysis to identify strain-specific, cross-disease, positive and negative associations. We find coronary artery disease, inflammatory bowel diseases, and liver cirrhosis to share gene-level signatures ascribed to the Streptococcus genus. Type 2 diabetes, by comparison, has a distinct metagenomic signature not linked to any one specific species or genus. We additionally find that at the species-level, the prior-reported connection between Solobacterium moorei and colorectal cancer is not consistently identified across models-however, our gene-level analysis unveils a group of robust, strain-specific gene associations. Finally, we validate our findings regarding colorectal cancer and inflammatory bowel diseases in independent cohorts and identify that features inversely associated with disease tend to be less reproducible than features enriched in disease. Overall, our work is not only a step towards gene-based, cross-disease microbiome diagnostic indicators, but it also illuminates the nuances of the genetic architecture of the human microbiome, including tension between gene- and species-level associations.

RevDate: 2021-05-24
CmpDate: 2021-05-24

Nearing JT, Comeau AM, MGI Langille (2021)

Identifying biases and their potential solutions in human microbiome studies.

Microbiome, 9(1):113.

Advances in DNA sequencing technology have vastly improved the ability of researchers to explore the microbial inhabitants of the human body. Unfortunately, while these studies have uncovered the importance of these microbial communities to our health, they often do not result in similar findings. One possible reason for the disagreement in these results is due to the multitude of systemic biases that are introduced during sequence-based microbiome studies. These biases begin with sample collection and continue to be introduced throughout the entire experiment leading to an observed community that is significantly altered from the true underlying microbial composition. In this review, we will highlight the various steps in typical sequence-based human microbiome studies where significant bias can be introduced, and we will review the current efforts within the field that aim to reduce the impact of these biases. Video abstract.

RevDate: 2021-05-17

Requena T, M Velasco (2021)

The human microbiome in sickness and in health.

Revista clinica espanola, 221(4):233-240.

The study of the human microbiome has led to an exceptional increase in the current understanding of the importance of microbiota for health throughout all stages of life. Human microbial colonization occurs in the skin, genitourinary system and, mainly, in the oral cavity and intestinal tract. In these locations, the human microbiota establishes a symbiotic relationship with the host and helps maintain physiological homeostasis. Lifestyle, age, diet and use of antibiotics are the main regulators of the composition and functionality of human microbiota. Recent studies have indicated the reduction in microbial diversity as one of the contributors to the development of diseases. In addition to phylogenetic diversity studies, further metagenomic studies are needed at the functional level of the human microbiome to improve our understanding of its involvement in human health.

RevDate: 2021-06-23

Herzig AF, Velo-Suárez L, Le Folgoc G, et al (2021)

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.

Genetic epidemiology, 45(5):537-548.

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.

RevDate: 2021-05-18

Li W, ZS Ma (2021)

Population-level diversity-disease relationship (p-DDR) in the human microbiome associated diseases.

Computational and structural biotechnology journal, 19:2297-2306.

Diversity-disease relationship (DDR) is a de facto standard analysis in the studies of human microbiome associated diseases (MADs). For example, the species richness or Shannon entropy are routinely compared between the healthy and diseased groups. Nevertheless, the basic scale of the standard diversity analysis is individual subject rather than a cohort or population because the diversity is computed for individual samples, not for the group. Here we aim to expand the current DDR study from individual focus to population level, which can offer important insights for understanding the epidemiology of MADs. We analyzed the diversity-disease relationship at cohort scale based on a collection of 23 datasets covering the major human MADs. Methodologically, we harness the power of a recent extension to the classic species-area relationship (SAR), i.e., the diversity-area relationship (DAR), to achieve the expansion from individual DDR to inter-subject diversity scaling analysis. Specifically, we apply the DAR analysis to estimate and compare the potentially maximal accrual diversities of the healthy and diseases groups, as well as the inter-subject diversity scaling parameters and the individual-to-population diversity ratios. It was shown that, except for the potential diversity (D max) at the cohort level in approximately 5.4% cases of MADs, DAR parameters displayed no significant differences between healthy and diseased treatments. That is, the DAR parameters are rather resilient against MADs, except for the potential diversity in some diseases. We compared our population-level DDR with the existing individual-level DDR patterns and proposed a hypothesis to interpret their differences.


RJR Experience and Expertise


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.


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.


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.


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.


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.


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.


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.


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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E-mail: RJR8222@gmail.com

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

short personal version

Curriculum Vitae for R J Robbins

long standard version

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