Microbiome differential abundance methods produce different results across 38 datasets

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 17, 2022

Identifying differentially abundant microbes is a common goal of microbiome studies. Multiple methods are used interchangeably for this purpose in the literature. Yet, there few large-scale studies systematically exploring appropriateness using these tools interchangeably, and scale significance differences between them. Here, we compare performance 14 differential abundance testing on 38 16S rRNA gene datasets with two sample groups. We test amplicon sequence variants operational taxonomic units (ASVs) Our findings confirm that identified drastically different numbers sets significant ASVs, results depend data pre-processing. For many number features correlate aspects data, such as size, sequencing depth, effect size community differences. ALDEx2 ANCOM-II produce most consistent across agree best intersect from approaches. Nevertheless, recommend researchers should use consensus approach based multiple to help ensure robust biological interpretations. Many available, but it lacks systematic comparison among authors groups, show results.

Язык: Английский

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Human gut bacteria produce ΤΗ17-modulating bile acid metabolites

Nature, Год журнала: 2022, Номер 603(7903), С. 907 - 912

Опубликована: Март 16, 2022

Язык: Английский

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Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

Nature Microbiology, Год журнала: 2021, Номер 6(11), С. 1367 - 1382

Опубликована: Окт. 21, 2021

Abstract Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and microbiota can impact host physiology in various ways, such as through production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine tyrosine) into their respective lactic (indolelactic acid, phenyllactic acid 4-hydroxyphenyllactic acid) via a previously unrecognized lactate dehydrogenase (ALDH). The ability to derivatives was confirmed using monocolonized mice. Longitudinal profiling faecal composition metabolome Danish infants ( n = 25), from birth until 6 months age, showed concentrations correlated positively with abundance human milk oligosaccharide-degrading containing ALDH, including longum , B. breve bifidum . We further -derived indolelactic associated capacity these samples activate vitro aryl hydrocarbon receptor (AhR), important controlling intestinal homoeostasis responses. Finally, show modulates ex vivo responses CD4 + T cells monocytes dose-dependent manner by acting an agonist both AhR hydroxycarboxylic 3 (HCA ). Our findings reveal produce suggest may function life.

Язык: Английский

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Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

Nature Medicine, Год журнала: 2022, Номер 28(3), С. 535 - 544

Опубликована: Фев. 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.

Язык: Английский

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MicrobiomeAnalyst 2.0: comprehensive statistical, functional and integrative analysis of microbiome data

Nucleic Acids Research, Год журнала: 2023, Номер 51(W1), С. W310 - W318

Опубликована: Май 11, 2023

Abstract Microbiome studies have become routine in biomedical, agricultural and environmental sciences with diverse aims, including diversity profiling, functional characterization, translational applications. The resulting complex, often multi-omics datasets demand powerful, yet user-friendly bioinformatics tools to reveal key patterns, important biomarkers, potential activities. Here we introduce MicrobiomeAnalyst 2.0 support comprehensive statistics, visualization, interpretation, integrative analysis of data outputs commonly generated from microbiome studies. Compared the previous version, features three new modules: (i) a Raw Data Processing module for amplicon processing taxonomy annotation that connects directly Marker Profiling downstream statistical analysis; (ii) Metabolomics help dissect associations between community compositions metabolic activities through joint paired metabolomics datasets; (iii) Statistical Meta-Analysis identify consistent signatures by integrating across multiple Other improvements include added multi-factor differential interactive visualizations popular graphical outputs, updated methods prediction correlation analysis, expanded taxon set libraries based on latest literature. These are demonstrated using dataset recent type 1 diabetes study. is freely available at microbiomeanalyst.ca.

Язык: Английский

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scCODA is a Bayesian model for compositional single-cell data analysis

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Ноя. 25, 2021

Compositional changes of cell types are main drivers biological processes. Their detection through single-cell experiments is difficult due to the compositionality data and low sample sizes. We introduce scCODA ( https://github.com/theislab/scCODA ), a Bayesian model addressing these issues enabling study complex type effects in disease, other stimuli. demonstrated excellent performance, while reliably controlling for false discoveries, identified experimentally verified that were missed original analyses.

Язык: Английский

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Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites

Gut, Год журнала: 2022, Номер 71(12), С. 2439 - 2450

Опубликована: Апрель 6, 2022

Objective Cigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites. Design Azoxymethane-treated C57BL/6 mice were exposed or clean air 2 hours per day 28 weeks. Shotgun metagenomic sequencing liquid chromatography mass spectrometry parallelly performed on stools alterations in Germ-free transplanted with from smoke-exposed smoke-free control mice. Results Mice had significantly increased tumour incidence cellular proliferation compared Gut microbial dysbiosis was observed significant differential abundance of bacterial species including enrichment Eggerthella lenta depletion Parabacteroides distasonis Lactobacillus spp. Metabolomic analysis showed bile acid metabolites, especially taurodeoxycholic (TDCA) colon found that E. most positive correlation TDCA Moreover, manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal‑regulated kinase 1/2) signalling (a downstream target TDCA) impaired barrier function. Furthermore, germ-free (GF-AOMS) colonocyte proliferation. Similarly, GF-AOMS abundances TDCA, activated pathway colonic epithelium. Conclusion The induced plays protumourigenic role CRC. smoke-induced altered metabolites function, which could activate

Язык: Английский

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Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 15, 2022

Abstract Parkinson’s disease (PD) may start in the gut and spread to brain. To investigate role of microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from end. We enrolled 490 PD 234 control individuals, deep shotgun sequencing fecal DNA, followed by metagenome-wide association studies requiring significance two (ANCOM-BC MaAsLin2) declare association, network analysis identify polymicrobial clusters, functional profiling. Here show that over 30% species, genes pathways tested have altered abundances PD, depicting widespread dysbiosis. PD-associated species form clusters grow or shrink together, some compete. microbiome is permissive, evidenced overabundance pathogens immunogenic components, dysregulated neuroactive signaling, preponderance molecules induce alpha-synuclein pathology, over-production toxicants; with reduction anti-inflammatory neuroprotective factors limiting capacity recover. validate, human findings were observed experimental models; reconcile resolve literature; provide broad foundation wealth concrete testable hypotheses discern PD.

Язык: Английский

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A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1

Cell Host & Microbe, Год журнала: 2021, Номер 29(9), С. 1366 - 1377.e9

Опубликована: Авг. 19, 2021

Язык: Английский

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Multi-kingdom microbiota analyses identify bacterial–fungal interactions and biomarkers of colorectal cancer across cohorts

Nature Microbiology, Год журнала: 2022, Номер 7(2), С. 238 - 250

Опубликована: Янв. 27, 2022

Abstract Despite recent progress in our understanding of the association between gut microbiome and colorectal cancer (CRC), multi-kingdom dysbiosis CRC across cohorts is unexplored. We investigated four-kingdom microbiota alterations using metagenomic datasets 1,368 samples from 8 distinct geographical cohorts. Integrated analysis identified 20 archaeal, 27 bacterial, fungal 21 viral species for each single-kingdom diagnostic model. However, data revealed superior accuracy models constructed with markers, particular addition species. Specifically, 16 markers including 11 4 1 archaeal feature, achieved good performance diagnosing patients (area under receiver operating characteristic curve (AUROC) = 0.83) maintained 3 independent Coabundance ecological network associations bacterial species, such as Talaromyces islandicus Clostridium saccharobutylicum . Using metagenome shotgun sequencing data, predictive power microbial functional potential was explored elevated D-amino acid metabolism butanoate were observed CRC. Interestingly, model based on EggNOG genes high (AUROC 0.86). Collectively, findings uncovered CRC-associated common demonstrate applicability tools and, potentially, therapeutic targets treatment

Язык: Английский

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