Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly DOI Creative Commons
Nicolai Karcher, Eleonora Nigro, Michal Punčochář

et al.

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: July 14, 2021

Abstract Background Akkermansia muciniphila is a human gut microbe with key role in the physiology of intestinal mucus layer and reported associations decreased body mass increased barrier function health. Despite its biomedical relevance, genomic diversity A. remains understudied that closely related species, except for glycaniphila , unexplored. Results We present large-scale population genomics analysis genus using 188 isolate genomes 2226 assembled from 18,600 metagenomes humans other animals. While we do not detect strains can be grouped into five distinct candidate including show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These species are likely human-specific, as they detected mice non-human primates almost exclusively when kept captivity. In humans, display ecological co-exclusion, diversified functional capabilities, patterns host mass. Analysis CRISPR-Cas loci reveals new variants spacers targeting newly discovered putative bacteriophages. Remarkably, observe an relative abundance cognate predicted bacteriophages present, suggesting interactions. further exhibits subspecies-level genetic stratification associated differences such exo/lipopolysaccharide operon. Conclusions uncover large phylogenetic humans. This variability should considered ongoing experimental metagenomic efforts to characterize health-associated properties bacteria.

Language: Английский

Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4 DOI Creative Commons
Aitor Blanco‐Míguez, Francesco Beghini, Fabio Cumbo

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(11), P. 1633 - 1644

Published: Feb. 23, 2023

Abstract Metagenomic assembly enables new organism discovery from microbial communities, but it can only capture few abundant organisms most metagenomes. Here we present MetaPhlAn 4, which integrates information metagenome assemblies and isolate genomes for more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01 M prokaryotic reference metagenome-assembled genomes, define unique marker genes 26,970 species-level genome bins, 4,992 them taxonomically unidentified at the species level. 4 explains ~20% reads in international human gut microbiomes >40% less-characterized environments such as rumen microbiome proves accurate than available alternatives on synthetic evaluations while also reliably quantifying with no cultured isolates. Application method to >24,500 metagenomes highlights previously undetected be strong biomarkers host conditions lifestyles mouse shows that even uncharacterized genetically profiled resolution single strains.

Language: Английский

Citations

545
Bifidobacteria-mediated immune system imprinting early in life DOI Creative Commons
Bethany M. Henrick, Lucie Rodriguez, Tadepally Lakshmikanth

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(15), P. 3884 - 3898.e11

Published: June 17, 2021

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that turn benefit host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare modern societies. Here we show a lack bifidobacteria, particular depletion genes required for human milk oligosaccharide (HMO) utilization from metagenome, is associated systemic inflammation dysregulation life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) Th17 cytokines were silenced interferon β (IFNβ) was induced. Fecal water EVC001-supplemented contains abundant indolelactate B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 Th2 cells during polarization, functional link between beneficial immunoregulation first months

Language: Английский

Citations

514
Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer DOI
Lisa Derosa, Bertrand Routy, Andrew Maltez Thomas

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(2), P. 315 - 324

Published: Feb. 1, 2022

Language: Английский

Citations

404
METABOLIC: high-throughput profiling of microbial genomes for functional traits, metabolism, biogeochemistry, and community-scale functional networks DOI Creative Commons
Zhichao Zhou, Patricia Q. Tran, Adam M. Breister

et al.

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: Feb. 16, 2022

Advances in microbiome science are being driven large part due to our ability study and infer microbial ecology from genomes reconstructed mixed communities using metagenomics single-cell genomics. Such omics-based techniques allow us read genomic blueprints of microorganisms, decipher their functional capacities activities, reconstruct roles biogeochemical processes. Currently available tools for analyses data can annotate depict metabolic functions some extent; however, no standardized approaches currently the comprehensive characterization predictions, metabolite exchanges, interactions, contributions cycling.

Language: Английский

Citations

370
Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation DOI Creative Commons
Sara Federici,

Sharon Kredo‐Russo,

Rafael Valdés‐Mas

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(16), P. 2879 - 2898.e24

Published: Aug. 1, 2022

Language: Английский

Citations

320
Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial DOI Creative Commons
Nazlı Dizman, Luís Meza, Paulo Gustavo Bergerot

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 704 - 712

Published: Feb. 28, 2022

Abstract Previous studies have suggested that the gut microbiome influences response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product we postulated could augment CPI through modulation of microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive metastatic renal cell carcinoma clear and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 receive nivolumab ipilimumab without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint compare relative abundance Bifidobacterium spp. baseline 12 weeks not met, no significant differences Shannon index associated addition nivolumab–ipilimumab detected. Secondary endpoints included rate, progression-free survival (PFS) toxicity. PFS significantly longer receiving than (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05–0.47, P = 0.001). Although statistically significant, rate also higher (58% 20%, 0.06). No difference toxicity observed between arms. data suggest appears enhance clinical outcome treated nivolumab–ipilimumab. Larger are warranted confirm observation elucidate mechanism action effects on immune compartments.

Language: Английский

Citations

319
Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade DOI
Miles C. Andrews, Connie P.M. Duong, Vancheswaran Gopalakrishnan

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(8), P. 1432 - 1441

Published: July 8, 2021

Language: Английский

Citations

295
Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma DOI Creative Commons
Karla A. Lee, Andrew Maltez Thomas, Laura A. Bolte

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(3), P. 535 - 544

Published: Feb. 28, 2022

Abstract The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on specific characteristics linked benefits ICIs. We performed shotgun metagenomic sequencing stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients advanced cutaneous melanoma ( n = 165). Integrating dataset 147 previously published studies, we found that a relevant, cohort-dependent, association response A machine learning analysis confirmed link between and overall rates (ORRs) progression-free survival (PFS) ICIs also revealed reproducibility microbiome-based signatures across cohorts. Accordingly, panel species, including Bifidobacterium pseudocatenulatum , Roseburia spp. Akkermansia muciniphila responders was identified, no single species could be regarded as fully consistent biomarker studies. Overall, role human in appears more complex than thought, extending beyond differing microbial simply present or absent nonresponders. Future studies should adopt larger sample sizes take into account interplay factors over treatment course.

Language: Английский

Citations

283
The person-to-person transmission landscape of the gut and oral microbiomes DOI Creative Commons
Mireia Vallès-Colomer, Aitor Blanco‐Míguez, Paolo Manghi

et al.

Nature, Journal Year: 2023, Volume and Issue: 614(7946), P. 125 - 135

Published: Jan. 18, 2023

Abstract The human microbiome is an integral component of the body and a co-determinant several health conditions 1,2 . However, extent to which interpersonal relations shape individual genetic makeup its transmission within across populations remains largely unknown 3,4 Here, capitalizing on more than 9,700 metagenomes computational strain-level profiling, we detected extensive bacterial strain sharing individuals (more 10 million instances) with distinct mother-to-infant, intra-household intra-population patterns. Mother-to-infant gut was considerable stable during infancy (around 50% same strains among shared species (strain-sharing rate)) remained detectable at older ages. By contrast, oral occurred horizontally enhanced by duration cohabitation. There substantial cohabiting individuals, 12% 32% median strain-sharing rates for microbiomes, time since cohabitation affected age or genetics did. Bacterial additionally recapitulated host population structures better species-level profiles Finally, taxa appeared as efficient spreaders modes were associated different predicted phenotypes linked out-of-host survival capabilities. microorganism that describe underscores relevance in studies 5 , especially those non-infectious, microbiome-associated diseases.

Language: Английский

Citations

250
Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer DOI Creative Commons
Joseph Tintelnot, Yang Xu, Till Robin Lesker

et al.

Nature, Journal Year: 2023, Volume and Issue: 615(7950), P. 168 - 174

Published: Feb. 22, 2023

Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing high incidence of metastatic disease and limited responses treatment1,2. Less than half all patients respond primary treatment for PDAC, chemotherapy3,4, genetic alterations alone cannot explain this5. Diet an environmental factor that can influence response therapies, but its role in PDAC unclear. Here, using shotgun metagenomic sequencing metabolomic screening, we show microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) enriched who treatment. Faecal microbiota transplantation, short-term dietary manipulation oral 3-IAA administration increase efficacy chemotherapy humanized gnotobiotic mouse models PDAC. Using a combination loss- gain-of-function experiments, licensed neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which with induces downregulation reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 7. All this results accumulation ROS autophagy cells, compromises their metabolic fitness and, ultimately, proliferation. In humans, observed significant correlation between levels therapy two independent cohorts. summary, identify has clinical implications provide motivation considering nutritional interventions during cancer.

Language: Английский

Citations

248