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

May 17, 2025

  • Irritable Bowel Syndrome (IBS)
    Irritable Bowel Syndrome (IBS)

    Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.

Last Updated: 2023

Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.

Location
United States of America
Sample Site
Feces
Species
Homo sapiens

What Was Studied?

This study investigated the multi-omics profiles of the intestinal microbiome in Irritable Bowel Syndrome (IBS) and its bowel habit subtypes. The researchers aimed to uncover distinct microbial compositions and functional differences in patients with IBS-D (diarrhea-predominant), IBS-C (constipation-predominant), and IBS-M (mixed), compared to healthy controls. This study utilized 16S rRNA sequencing, metatranscriptomics, and untargeted metabolomics to capture both compositional and functional microbial changes. A cohort of 318 IBS patients and 177 healthy controls provided fecal samples, which were analyzed for microbial taxa, gene expression, and metabolic products.

Who Was Studied?

The study included 318 IBS patients, categorized into IBS-D, IBS-C, and IBS-M, alongside 177 healthy controls. These participants were recruited from diverse backgrounds and matched by age, gender, BMI, diet, and anxiety levels to minimize confounding factors. The study used comprehensive multi-omics approaches to investigate microbiome signatures, functional gene expression, and metabolic profiles in these individuals.

What Were the Most Important Findings?

The study identified distinct multi-omics microbial signatures in IBS patients compared to healthy controls. IBS-D patients exhibited increased levels of Bacteroides dorei, alterations in succinate and mannose metabolism, and elevated polyamine synthesis, which are associated with diarrhea severity. Meanwhile, IBS-C patients showed distinct upregulation of butyrate-producing pathways and enrichment in Verrucomicrobiota. The metatranscriptomics analysis revealed heightened expression of genes involved in fructose and polyol metabolism across all IBS subtypes, suggesting a microbiome-driven enhancement of fermentable carbohydrate utilization. Additionally, metabolomic profiling showed increased tyramine, gentisate, and hydrocinnamate in IBS patients, suggesting disruptions in aromatic amino acid metabolism. The multi-omics classifier developed from these findings demonstrated high accuracy (AUC 0.82) in distinguishing IBS patients from healthy controls. Further subclassification models effectively differentiated IBS-D from IBS-C with 86% accuracy, highlighting the role of bile acids, polyamines, and SCFA pathways in bowel habit variability.

ParameterFindings in IBS-DFindings in IBS-CFindings in IBS-M
Bacterial DiversityAltered diversity with increased Bacteroides doreiElevated Verrucomicrobiota and butyrate-producing pathwaysMixed microbial shifts with no clear dominant phylum
Key GeneraEnrichment of Bacteroides dorei, reduction in anti-inflammatory taxaIncreased Verrucomicrobiota and SCFA producersVariable populations of Firmicutes and Bacteroidetes
Metabolic PathwaysEnhanced succinate and mannose metabolism; elevated polyamine synthesisUpregulation of butyrate-producing pathwaysMixed shifts in carbohydrate fermentation and SCFA production
Metatranscriptomics AnalysisHigher expression of genes involved in fructose and polyol metabolismButyrate synthesis pathways more prominentElevated expression of pathways linked to bile acid metabolism
Metabolomic ShiftsIncreased levels of tyramine, gentisate, and hydrocinnamateElevated levels of butyrate and palmitoleateMixed aromatic amino acid metabolism alterations
Inflammatory AssociationsLinked to diarrhea severity through succinate and bile acid dysregulationLinked to constipation through lipid metabolismMixed inflammation markers reflective of both diarrhea and constipation
Diagnostic PotentialMulti-omics classifier with 86% accuracy in distinguishing IBS-DEffective biomarker profiles for IBS-CSubtype differentiation through SCFA and bile acid pathways

What Are the Greatest Implications of This Study?

This study’s findings underscore the role of gut microbiome dysbiosis in IBS pathophysiology, driven by specific metabolic and transcriptional shifts. The identification of subtype-specific microbial signatures highlights the potential for personalized microbiome-based diagnostics and targeted dietary interventions. Notably, the association between fermentable carbohydrate metabolism and symptom severity suggests that dietary modifications—such as low-FODMAP or specific carbohydrate restriction—could be effective therapeutic strategies. Additionally, the development of a multi-omics classifier with high diagnostic accuracy presents a promising non-invasive approach for IBS diagnosis and subtype differentiation.

Irritable Bowel Syndrome (IBS)

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by symptoms such as abdominal pain, bloating, and altered bowel habits. Recent research has focused on the gut microbiota's role in IBS, aiming to identify specific microbial signatures associated with the condition.

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