Association of distinct microbial and metabolic signatures with microscopic colitis
Albert Sheng-Yin Chen1,2, Hanseul Kim1,2,3, Etienne Nzabarushimana1,2,3
1Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine that primarily affects older adults and presents with chronic diarrhea. The etiology is unknown and there are currently no FDA approved medications or biomarkers for treatment or monitoring of the disease. Emerging evidence have implicated the gut microbiome and metabolome disturbances in MC pathogenesis. We conduct a comprehensive analysis of gut microbial and metabolic changes in a cohort of 683 participants, including 131 patients with active MC, 159 with chronic diarrhea, and 393 age- and sex-matched controls without diarrhea. Stool microbiome and metabolome are profiled using whole-genome shotgun metagenomic sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Compared to controls, eight microbial species including pro-inflammatory oral-typical Veillonella dispar and Haemophilus parainfluenzae, and 11 species, including anti-inflammatory Blautia glucerasea and Bacteroides stercoris are enriched and depleted in MC, respectively. Pro-inflammatory metabolites, including lactosylceramides, ceramides, lysophospholipids, and lysoplasmalogens, are enriched in active MC. Multi-omics analyses reveal robust associations between microbial species, metabolic pathways, and metabolites, suggesting concordant disruptions in MC. Here, we show distinct shifts in gut microbiome and metabolome in MC that can inform the development of non-invasive biomarkers and novel therapeutics.
Insights
Microscopic colitis (MC) involves gut microbiome and metabolome changes. This study reveals distinct microbial and metabolic shifts in MC patients, offering potential for new diagnostic biomarkers and treatments.
Area of Science:
- Gastroenterology
- Microbiology
- Metabolomics
Background:
- Microscopic colitis (MC) is a chronic inflammatory bowel disease causing chronic diarrhea.
- The exact causes of MC are unknown, with no current FDA-approved treatments or biomarkers.
- Emerging research suggests gut microbiome and metabolome alterations play a role in MC pathogenesis.
Purpose of the Study:
- To comprehensively analyze gut microbial and metabolic profiles in patients with active MC, chronic diarrhea, and healthy controls.
- To identify specific microbial species and metabolites associated with MC.
- To explore the relationship between microbiome, metabolome, and MC.
Main Methods:
- Analysis of stool samples from 683 participants (131 active MC, 159 chronic diarrhea, 393 controls).
- Whole-genome shotgun metagenomic sequencing for microbiome profiling.
- Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) for metabolome profiling.
Main Results:
- Significant differences in microbial composition were observed between MC patients and controls.
- Specific pro-inflammatory bacteria (e.g., Veillonella dispar) were enriched, while anti-inflammatory bacteria (e.g., Blautia glucerasea) were depleted in MC.
- Pro-inflammatory metabolites, including ceramides and lysophospholipids, were elevated in active MC patients.
- Multi-omics analysis demonstrated strong correlations between microbial shifts, metabolic pathways, and metabolite levels in MC.
Conclusions:
- Distinct alterations in the gut microbiome and metabolome characterize microscopic colitis.
- These findings suggest potential for developing non-invasive biomarkers for MC diagnosis and monitoring.
- The identified microbial and metabolic signatures may guide the development of novel therapeutic strategies for MC.
