The Emerging Short Chain Fatty Acid Enriched Metabotype in Irritable Bowel Syndrome and Its Potential Clinical...

Area of Science:

• Gastroenterology
• Microbiome Research
• Metabolomics

Background:

• Irritable bowel syndrome (IBS) studies show metabotypes enriched in fecal short-chain fatty acids (SCFAs).
• The role of SCFAs in IBS pathophysiology, whether as a marker of rapid transit or active contributor, remains unclear.

Purpose of the Study:

• Identify an SCFA-enriched metabotype in patients with moderate-to-severe IBS with diarrhea (IBS-D).
• Assess the association of this metabotype with clinical severity, gut transit time, and microbiome features.

Main Methods:

• Cross-sectional analysis of baseline data from the TRITON trial (ISRCTN17508514).
• Fecal volatile organic compounds profiled by gas chromatography-mass spectrometry (GC-MS).
• Microbiome characterized by whole-genome shotgun metagenomic sequencing; metabotypes identified using unsupervised hierarchical clustering and non-negative matrix factorization (NMF).

Main Results:

• An SCFA-enriched metabotype was identified in 31.7% of participants.
• This metabotype correlated with increased abdominal pain, urgency, stool frequency, and faster whole-gut transit.
• SCFA abundance positively correlated with symptom severity and inversely with transit time; distinct microbiome signatures were associated with SCFA-rich and SCFA-poor metabotypes.

Conclusions:

• A fecal metabotype enriched in SCFAs is associated with an IBS-D phenotype.
• This phenotype is characterized by pain, urgency, rapid transit, and higher stool frequency.