Article information
- Authors: Ma W, Wang Y, Nguyen LH, Mehta RS, Ha J, Bhosle A, Mclver LJ, Song M, Clish CB, Strate LL, Huttenhower C, Chan AT
- Journal: Nature Communications
- Year: 2024
- Volume: 15
- Page number(s): 3612
- DOI: 10.1038/s41467-024-47859-4
Study at a glance
- Study type: Nested case-control study
- Number of studies: Not applicable
- Participants: 242 women (121 with diverticulitis, 121 controls)
- Population studied: Women aged approximately 65 years from the Nurses’ Health Study II who provided stool samples
- Intervention: Not applicable (observational study)
- Comparator: Matched controls without diverticulitis
- Follow-up duration: Cross-sectional analysis of stool samples collected between February 2019 and July 2021
- Primary outcome(s): Differences in gut microbiome composition and stool metabolite profiles between women with and without diverticulitis
Why was this study done?
Diverticulitis, inflammation of pouches in the colon, is among the most common gastrointestinal disorders, yet its underlying causes remain poorly understood. The condition shares symptoms and inflammatory features with other bowel disorders such as inflammatory bowel disease, where gut bacteria disturbances have been identified as important contributors.
Ma and colleagues examined whether alterations in the gut microbiome and their metabolic products might play a role in diverticulitis, and explored how diet and gut bacteria might interact to influence disease risk.
How was the study performed?
The researchers conducted a nested case-control study within the Nurses’ Health Study II, identifying 121 women who developed diverticulitis requiring antibiotics or hospitalisation and matching them to 121 women without diverticulitis based on age, race and sample collection month.
The team performed shotgun metagenomic sequencing on stool samples to characterise the gut microbiome and conducted untargeted metabolomics profiling to identify chemical compounds. Analyses were adjusted for body mass index, physical activity, diet quality, fibre intake and antibiotic use.
What did the researchers find?
Gut microbial community structure and metabolic profiles differed modestly between women with diverticulitis and controls. Women with diverticulitis showed reduced species richness.
Several bacterial species were altered. The researchers found enrichment of inflammation-associated bacteria, including Ruminococcus gnavus, several Clostridium species, Erysipelatoclostridium ramosum and Hungatella hathewayi. Beneficial butyrate-producing bacteria were depleted, including Eubacterium eligens, Faecalibacterium species and Subdoligranulum species. Parasutterella excrementihominis was also reduced.
Metabolite analysis revealed increased histidine-related compounds (3-methylhistidine and N-acetylhistamine), 1,7-dimethyluric acid and docosapentaenoic acid. Women with diverticulitis had reduced ceramides, stearic acid and several other metabolites.
The study found enrichment of microbial pathways involved in fatty acid biosynthesis. The protective effect of dietary fibre and a prudent diet (characterised by vegetables, legumes, fruit and fish) against diverticulitis was stronger in women with particular microbial configurations, especially high Bacteroides uniformis levels.
Microbe-metabolite relationships differed between groups. Bilophila wadsworthia, which typically responds to dietary fat and metabolises bile acids, showed altered relationships with bile acids in diverticulitis.
What did the authors conclude?
The authors concluded this study provides evidence of alterations in gut microbiome composition, functions and metabolic activity in diverticulitis, particularly involving inflammation and lipid metabolism. The gut microbiome appears to modulate dietary effects on diverticulitis risk, with microbial composition influencing how fibre and prudent dietary patterns affect disease susceptibility.
The findings offer insights into inflammation-related microbial and metabolic signatures and support developing microbiome-based diagnostic tools and therapeutic targets. Additional research, including validation in broader populations and prospective studies, is needed to advance personalised microbiome-informed dietary interventions or therapeutic manipulation of gut bacteria.
The authors acknowledged limitations including the cross-sectional design, which could not determine whether microbial changes preceded or followed diverticulitis development. The study examined only women and used stool samples rather than tissue samples.
Key takeaways
- Women with diverticulitis showed distinct gut microbiome and metabolite profiles, including enrichment of inflammation-associated bacteria and depletion of beneficial butyrate-producing species.
- Metabolic changes included increased histidine-related compounds and 1,7-dimethyluric acid, alongside reduced ceramides and other lipid markers.
- Dietary fibre’s protective association with diverticulitis was modulated by gut microbiome composition, with stronger benefits in women carrying certain bacterial profiles, particularly high Bacteroides uniformis levels.
- Microbe-metabolite relationships differed in diverticulitis, suggesting altered bacterial metabolism may contribute to disease development.
- These findings support developing microbiome-based approaches for preventing or treating diverticulitis, though further prospective research is needed.
This Scientific Publication Summary is an objective summary of the published study for personal and educational use. It does not constitute medical advice, endorsement of the intervention, or a recommendation to alter clinical practice.