Dataset Information

A Metagenome-Wide Association Study of Gut Microbiome in Patients With Multiple Sclerosis Revealed Novel Disease Pathology.

ABSTRACT: While microbiome plays key roles in the etiology of multiple sclerosis (MS), its mechanism remains elusive. Here, we conducted a comprehensive metagenome-wide association study (MWAS) of the relapsing-remitting MS gut microbiome (n _case = 26, n _control = 77) in the Japanese population, by using whole-genome shotgun sequencing. Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis, and pathway analysis). Phylogenetic case-control association tests showed discrepancies of eight clades, most of which were related to the immune system (false discovery rate [FDR] < 0.10; e.g., Erysipelatoclostridium_sp. and Gemella morbillorum). Gene association tests found an increased abundance of one putative dehydrogenase gene (Clo1100_2356) and one ABC transporter related gene (Mahau_1952) in the MS metagenome compared with controls (FDR < 0.1). Molecular pathway analysis of the microbiome gene case-control comparisons identified enrichment of multiple Gene Ontology terms, with the most significant enrichment on cell outer membrane (P = 1.5 × 10^-7). Interaction between the metagenome and host genome was identified by comparing biological pathway enrichment between the MS MWAS and the MS genome-wide association study (GWAS) results (i.e., MWAS-GWAS interaction). No apparent discrepancies in alpha or beta diversities of metagenome were found between MS cases and controls. Our shotgun sequencing-based MWAS highlights novel characteristics of the MS gut microbiome and its interaction with host genome, which contributes to our understanding of the microbiome's role in MS pathophysiology.

SUBMITTER: Kishikawa T

PROVIDER: S-EPMC7759502 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Metagenome-Wide Association Study of Gut Microbiome in Patients With Multiple Sclerosis Revealed Novel Disease Pathology.

Kishikawa Toshihiro T Ogawa Kotaro K Motooka Daisuke D Hosokawa Akiko A Kinoshita Makoto M Suzuki Ken K Yamamoto Kenichi K Masuda Tatsuo T Matsumoto Yuki Y Nii Takuro T Maeda Yuichi Y Nakamura Shota S Inohara Hidenori H Mochizuki Hideki H Okuno Tatsusada T Okada Yukinori Y

Frontiers in cellular and infection microbiology 20201211

While microbiome plays key roles in the etiology of multiple sclerosis (MS), its mechanism remains elusive. Here, we conducted a comprehensive metagenome-wide association study (MWAS) of the relapsing-remitting MS gut microbiome (ncase = 26, ncontrol = 77) in the Japanese population, by using whole-genome shotgun sequencing. Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis, and pathway analysis ...[more]

PMID: 33363050

Similar Datasets

Project description:Pigs are among the most numerous and intensively farmed food-producing animals in the world. The gut microbiome plays an important role in the health and performance of swine and changes rapidly after weaning. Here, fecal samples were collected from pigs at 7 different times points from 7 to 140 days of age. These swine fecal metagenomes were used to assemble 1,150 dereplicated metagenome-assembled genomes (MAGs) that were at least 90% complete and had less than 5% contamination. These MAGs represented 472 archaeal and bacterial species, and the most widely distributed MAGs were the uncultured species Collinsella sp002391315, Sodaliphilus sp004557565, and Prevotella sp000434975. Weaning was associated with a decrease in the relative abundance of 69 MAGs (e.g., Escherichia coli) and an increase in the relative abundance of 140 MAGs (e.g., Clostridium sp000435835, Oliverpabstia intestinalis). Genes encoding for the production of the short-chain fatty acids acetate, butyrate, and propionate were identified in 68.5%, 18.8%, and 8.3% of the MAGs, respectively. Carbohydrate-active enzymes associated with the degradation of arabinose oligosaccharides and mixed-linkage glucans were predicted to be most prevalent among the MAGs. Antimicrobial resistance genes were detected in 327 MAGs, including 59 MAGs with tetracycline resistance genes commonly associated with pigs, such as tet(44), tet(Q), and tet(W). Overall, 82% of the MAGs were assigned to species that lack cultured representatives indicating that a large portion of the swine gut microbiome is still poorly characterized. The results here also demonstrate the value of MAGs in adding genomic context to gut microbiomes. IMPORTANCE Many of the bacterial strains found in the mammalian gut are difficult to culture and isolate due to their various growth and nutrient requirements that are frequently unknown. Here, we assembled strain-level genomes from short metagenomic sequences, so-called metagenome-assembled genomes (MAGs), that were derived from fecal samples collected from pigs at multiple time points. The genomic context of a number of antimicrobial resistance genes commonly detected in swine was also determined. In addition, our study connected taxonomy with potential metabolic functions such as carbohydrate degradation and short-chain fatty acid production.

Project description:BackgroundThe gut microbiome is important in the development and immunotherapy efficacy of lung cancer. However, the relationship between the intestinal flora and chemotherapy outcomes remains unclear and was investigated in this study.MethodsWe analyzed baseline stool samples from patients with locally advanced and advanced lung cancer before chemotherapy treatment, through metagenomics of the gut microbiota. The composition, diversity, function, and metabolic pathway analysis were compared among patients with different clinical outcomes.ResultsFrom 64 patients, 33 responded to treatment (responders) and 31 did not (nonresponders). Streptococcus mutans and Enterococcus casseliflavus were enriched in responders (P < 0.05), while 11 bacteria including Leuconostoc lactis and Eubacterium siraeum were enriched in nonresponders (P < 0.05) by variance analysis. Responders were associated with significantly higher Acidobacteria and Granulicella, while Streptococcus oligofermentans, Megasphaera micronuciformis, and Eubacterium siraeum were more abundant in nonresponders by Lefse analysis. Streptococcus mutans and Enterococcus casseliflavus were further identified as bacterial markers relevant to responders using unsupervised clustering, and Leuconostoc lactis and Eubacterium siraeum were related to nonresponders. The L-glutamate degradation VIII pathway was enriched in responders (P = 0.014), and the C4 photosynthetic carbon assimilation cycle, reductive TCA cycle I, and hexitol fermentation to lactate, formate, ethanol, and acetate were enriched in nonresponders (P < 0.05). Additionally, significant associations of bacterial species with clinical phenotypes were observed by Spearman correlation analysis.ConclusionsThe specific gut microbiome of patients with lung cancer might be connected to the clinical outcomes of chemotherapy.Key pointsSignificant findings of the study Lung cancer patients with different gut microbiome compositions and microbiome metabolic pathways have different responses to chemotherapy. Microbiome species are also associated with different lung cancer clinical phenotypes. What this study adds We have identified specific gut microbiome species that can be used as relevant biomarkers for chemotherapy outcomes. This can potentially be used to guide clinical treatment decisions.

Project description:BackgroundMultiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder.MethodsWe performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants.FindingsTogether with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals.InterpretationOur study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker.FundingThis work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Dataset Information

A Metagenome-Wide Association Study of Gut Microbiome in Patients With Multiple Sclerosis Revealed Novel Disease Pathology.

Publications

A Metagenome-Wide Association Study of Gut Microbiome in Patients With Multiple Sclerosis Revealed Novel Disease Pathology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets