Alterations in gut microbiome composition and function in irritable bowel syndrome and increased probiotic abundance with daily supplementation

Phan, Joann; Nair, Divya; Jain, Suneer; Montagne, Thibaut; Flores, Demi Valeria; Nguyen, Andre; Dietsche, Summer; Gombar, Saurabh; Cotter, Philip D.

doi:10.1101/2021.09.02.458777

Cited by 1 publication

(3 citation statements)

References 99 publications

(109 reference statements)

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“…including A. odontolyticus as seen here [7]. Additional species level microbial shifts detected by 16S sequencing or metatranscriptomics that have been previously noted in large shotgun metagenomics studies include increased Streptococcus species (S. parasanguinis), Eggerthella lenta, and Blautia hydrogenotrophica as well as reduced Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bilophila wadsworthia [11,16,23]. Other taxonomic shifts observed in this study have not been previously reported and many taxa that were reported in prior studies were not significant in our study.…”

Section: Discussionsupporting

confidence: 64%

“…These differences could reflect multiple factors that differentiated our study including racial/ethnic composition, recruitment of subjects from the community rather than specialty clinics, and differences in analytical approach. Importantly, this study differed from many prior ones in using multivariate strategies to adjust for a wide range of covariates differing between IBS and HC that could confound analyses [7,11,[13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…Large studies of microbiome composition by 16S rRNA gene sequencing or shotgun metagenomics have in some cases shown minimal diversity change and taxonomic associations with IBS, while others have reported reduced diversity and taxonomic shifts that were not consistent across studies [6][7][8][9][10]. Recent studies have shifted to focus on functional characterization of the microbiome by shotgun metagenomics, which assesses functional potential by microbial gene content, or metabolomics, which assesses products of bacterial metabolism detected in feces [7,[11][12][13][14][15][16]. While these studies have reported significant shifts in gene content and metabolites, the specific features have not been consistent across studies.…”

Section: Introductionmentioning

confidence: 99%

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Multi-omics profiles of the intestinal microbiome in irritable bowel syndrome and its bowel habit subtypes

et al. 2023

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Background Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. As prior studies have primarily focused on composition, we hypothesized that multi-omics assessment of microbial function incorporating both metatranscriptomics and metabolomics would further delineate microbial profiles of IBS and its subtypes. Methods Fecal samples were collected from a racially/ethnically diverse cohort of 495 subjects, including 318 IBS patients and 177 healthy controls, for analysis by 16S rRNA gene sequencing (n = 486), metatranscriptomics (n = 327), and untargeted metabolomics (n = 368). Differentially abundant microbes, predicted genes, transcripts, and metabolites in IBS were identified by multivariate models incorporating age, sex, race/ethnicity, BMI, diet, and HAD-Anxiety. Inter-omic functional relationships were assessed by transcript/gene ratios and microbial metabolic modeling. Differential features were used to construct random forests classifiers. Results IBS was associated with global alterations in microbiome composition by 16S rRNA sequencing and metatranscriptomics, and in microbiome function by predicted metagenomics, metatranscriptomics, and metabolomics. After adjusting for age, sex, race/ethnicity, BMI, diet, and anxiety, IBS was associated with differential abundance of bacterial taxa such as Bacteroides dorei; metabolites including increased tyramine and decreased gentisate and hydrocinnamate; and transcripts related to fructooligosaccharide and polyol utilization. IBS further showed transcriptional upregulation of enzymes involved in fructose and glucan metabolism as well as the succinate pathway of carbohydrate fermentation. A multi-omics classifier for IBS had significantly higher accuracy (AUC 0.82) than classifiers using individual datasets. Diarrhea-predominant IBS (IBS-D) demonstrated shifts in the metatranscriptome and metabolome including increased bile acids, polyamines, succinate pathway intermediates (malate, fumarate), and transcripts involved in fructose, mannose, and polyol metabolism compared to constipation-predominant IBS (IBS-C). A classifier incorporating metabolites and gene-normalized transcripts differentiated IBS-D from IBS-C with high accuracy (AUC 0.86). Conclusions IBS is characterized by a multi-omics microbial signature indicating increased capacity to utilize fermentable carbohydrates—consistent with the clinical benefit of diets restricting this energy source—that also includes multiple previously unrecognized metabolites and metabolic pathways. These findings support the need for integrative assessment of microbial function to investigate the microbiome in IBS and identify novel microbiome-related therapeutic targets.

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Section: Discussionsupporting

confidence: 64%