Exclusive cataloging of near-complete genomes unveils novel functional insights into the human gut microbiome DOI Open Access
Junyeong Ma, Nayeon Kim,

Jun Hyung

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Abstract Understanding the human gut microbiome requires comprehensive genomic catalogs, yet many existing ones lack geographic diversity and include numerous medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of regions, potentially leading inaccurate functional insights into microbiome. To address these limitations, we developed an enhanced Human Reference Gut Microbiome (HRGM2), a catalog near-complete (NC) MAGs (completeness ≥90% contamination ≤5%) isolate (collectively ‘NC genomes’) with extensive sampling. HRGM2 comprises 155,211 non-redundant NC from 4,824 prokaryotic species across 41 countries, representing 66% increase in genome count boost over genome-based Unified Gastrointestinal Genome catalog. Extensive sampling Africa revealed previously undetectable Africa-associated phyla, highlighting microbial links between humans environment. Given high complexity microbiota, DNA-based profiling using outperforms marker-based accuracy. Profiling protein annotations provides reliable Notably, exclusive use genomes, enhances assessments microbiota metabolic capacities supports genome-scale models (GEMs) entire microbiota. These findings offer novel perspectives on microbiome, achievable only through high-quality cataloging.

Язык: Английский

Temporary dietary fiber depletion prompts rapid and lasting gut microbiota restructuring in mice DOI Creative Commons
Craig Rous,

Julie Cadiou,

Hiba Yazbek

и другие.

Microbiology Spectrum, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

ABSTRACT Long-term alterations of the gut microbiota and host symbiosis after a dietary perturbation remain insufficiently understood characterized. In this study, we investigate impact temporary fiber depletion in mice that received diet with reduced content (RFD) for 3 weeks followed by return to standard chow 6 weeks, compared only diet. Fiber deprivation was accompanied reduction diversity an increase mucolytic sulfate-reducing bacteria. The activities enzymes targeting glycans from mucus were increased accordingly, while those plant fibers decreased. On side, report transiently higher quantities DNA feces during RFD suggesting impaired barrier function. Six diet, lasting changes composition observed, as exemplified replacement durably depleted amplicon sequence variants close Duncaniella dubosii other members Muribaculaceae family. observation two distinct microbial communities under identical environmental alimentary conditions at end experiment suggests existence alternative stable states. IMPORTANCE article, authors explore on microbiota-host mouse model. More importantly, they examine resilience intestinal (chow) Some measured parameters (intestinal impairment bacterial glycan-degrading enzymatic activities) returned control values. However, not case richness—the number different bacteria observed—which remained reduced. Among related bacteria, some groups receded undetected until others saw their abundance replacement. find little can cause transition state, i.e., change composition.

Язык: Английский

Процитировано

0

Living on the edge: Mucus-associated microbes in the colon DOI Creative Commons
Mihovil Joja, Erica T. Grant, Mahesh S. Desai

и другие.

Mucosal Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

The colonic mucus layer acts as a physicochemical barrier to pathogen invasion and habitat for mucus-associated microbes. This mucosal microbiome plays crucial role in moderating production, maintaining integrity, shaping the host immune response. However, unchecked mucin foraging may render vulnerable disease. To better understand these dynamics layer, it is essential advance fundamental knowledge on how commensals bind utilize well their interactions with both microbial neighbors. We present an overview of approaches surveying bacteria assessing mucin-utilizing capacity, alongside discussion limitations existing methods. Additionally, we highlight diet secretory immunoglobulin A interact bacterial community colon. Insights into this subset can guide therapeutic strategies optimally support modulate integrity.

Язык: Английский

Процитировано

0

Next-generation IgA-SEQ allows for high-throughput, anaerobic, and metagenomic assessment of IgA-coated bacteria DOI Creative Commons
Merel van Gogh,

J Louwers,

Anna Celli

и другие.

Microbiome, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 21, 2024

The intestinal microbiota plays a significant role in maintaining systemic and homeostasis, but can also influence diseases such as inflammatory bowel disease (IBD) cancer. Certain bacterial species within the tract chronically activate immune system, leading to low-grade inflammation. As result, plasma cells produce high levels of secretory antigen-specific immunoglobulin A (IgA), which coats immunostimulatory bacteria. This IgA response against bacteria may be associated with maintenance homeostasis health, well disease. Unraveling this dichotomy identifying is crucial for understanding relationship between their health IgA-SEQ technology has successfully identified immunostimulatory, IgA-coated from fecal material. However, original time-consuming limited downstream applications. In study, we aimed develop next-generation, high-throughput, magnet-based sorting approach (ng-IgA-SEQ) overcome limitations protocol.

Язык: Английский

Процитировано

2

Long-term fasting remodels gut microbial metabolism and host metabolism DOI Creative Commons

QR Ducarmon,

Florian M. W. Grundler,

C Giannopoulou

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 19, 2024

Abstract Long-term fasting has become a promising research subject for its potential of treating and preventing metabolic diseases. However, little is known about impact on the functional capacity gut microbiome combined effect serum metabolome. Here, we demonstrate extensive remodelling microbial ecosystem in humans (n=92) after an average 9.8 days (∼250 kcal / day). Fasting transiently affected relative abundance majority bacterial species (306 decreased 210 increased out 772). Species changes could largely be explained by their genomic repertoire carbohydrate-active enzymes (CAZymes), which were investigated here first time. induced CAZyme families, depleting families with dietary fibre substrates increasing host-derived glycan substrates. Likewise, observed metabolome, 382 721 metabolites significantly (246 136 decreased). In-depth metagenome-metabolome co-variation analysis suggested Oscillibacter to key producers indole-3-propionic acid, crucial metabolite cardiometabolic health. Together, our results provide unprecedented view long-term composition function.

Язык: Английский

Процитировано

1

Unraveling interindividual differences and functional consequences of gut microbial metabolism of immunosuppressants DOI Open Access
Maral Baghai Arassi, Nicolai Karcher, Eleonora Mastrorilli

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

Abstract A major challenge in kidney transplantation (KT) is the large interpatient variability pharmacokinetics of immunosuppressive drugs. Here, we explored role gut microbiome interindividual variation drug metabolism. Analysis 38 fecal communities, including 10 from KT recipients, and 45 bacterial species against 25 drugs, revealed significant drug-specific differences Notably, 15 16 immunosuppressants tested were metabolized by at least one microbial community, found specific species, such as Bacteroides uniformis , to be potent metabolizers. We identified 18 different metabolites for two previously undescribed sirolimus everolimus. Our study reveals functional impact metabolism on key immunosuppressants, inactivation tacrolimus, activation potential increase toxicity mycophenolate mofetil (MMF), shows that metabolite methylprednisolone exhibits a 2.6-fold epithelial permeability compared parent drug. Through gain-of-function genetic screen B. enzyme BACUNI_RS05305 responsible MMF activation. Using machine learning model community metabolism, abundance features prevalent predicted biotransformation some drugs well, while others, priori experimental information genes protein structures led improved predictions. research highlights explain therapies sets stage clinical trials identify microbiome-encoded signatures predictive patients.

Язык: Английский

Процитировано

0

Health benefits of a five-day at-home modified fasting program: a randomised controlled trial DOI Creative Commons
Franziska Grundler, Quinten R. Ducarmon,

Alfred Holley

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

ABSTRACT Background Fasting has been shown to be one of the most cost-effective methods improve cardiometabolic health. We studied a 5-day hypocaloric (∼600 kcal/day) and ketogenic, modified fasting program (MFP) for at-home interventions. hypothesised that this MFP induces metabolic changes comparable 5 days prolonged (75-250kcal/day). Methods tested in two-arm randomised controlled trial where sixty-four healthy subjects were or control group. Serum biochemistry analyses questionnaires allowed determining effects on risk factors. Emotional well-being, possible side physical activity assessed with questionnaires. Biological pathways processes explored nuclear magnetic resonance blood metabolomics gut metagenomics analyses. Results participants (n=32) experienced weight loss (−3.1 ± 1.1 kg) persisting month after intervention. The induced significant, but transient reductions, systolic (−6.4 11.5 mmHg) diastolic (−4.4 7.7 pressure, glucose levels, HbA1c coagulation led greater reductions BMI (p=0.006), pressure (p = 0.009), cholesterol 0.02), LDL 0.02) individuals at diseases compared individuals. Total cholesterol, LDL-C HDL-C levels continued decreasing during food reintroduction. also increased emotional well-being. Blood revealed significant decrease chronic inflammation markers. Shotgun microbiome showed trends relative abundance majority bacterial species their genomic repertoire carbohydrate-active enzymes (CAZymes). This reflected families metabolising dietary fibre substrates an increase host-derived glycan substrates. Comparing previous cohort’s similar changes. Conclusion is safe effectively improves health well-being It offers benefits those observed clinic. practised home, widely accessible compatible individuals’ everyday life.

Язык: Английский

Процитировано

0

Exclusive cataloging of near-complete genomes unveils novel functional insights into the human gut microbiome DOI Open Access
Junyeong Ma, Nayeon Kim,

Jun Hyung

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Abstract Understanding the human gut microbiome requires comprehensive genomic catalogs, yet many existing ones lack geographic diversity and include numerous medium-quality metagenome-assembled genomes (MAGs) missing up to 50% of regions, potentially leading inaccurate functional insights into microbiome. To address these limitations, we developed an enhanced Human Reference Gut Microbiome (HRGM2), a catalog near-complete (NC) MAGs (completeness ≥90% contamination ≤5%) isolate (collectively ‘NC genomes’) with extensive sampling. HRGM2 comprises 155,211 non-redundant NC from 4,824 prokaryotic species across 41 countries, representing 66% increase in genome count boost over genome-based Unified Gastrointestinal Genome catalog. Extensive sampling Africa revealed previously undetectable Africa-associated phyla, highlighting microbial links between humans environment. Given high complexity microbiota, DNA-based profiling using outperforms marker-based accuracy. Profiling protein annotations provides reliable Notably, exclusive use genomes, enhances assessments microbiota metabolic capacities supports genome-scale models (GEMs) entire microbiota. These findings offer novel perspectives on microbiome, achievable only through high-quality cataloging.

Язык: Английский

Процитировано

0