Reduction of butyric acid-producing bacteria in the ileal mucosa-associated microbiota is associated with the history of abdominal surgery in patients with Crohn's disease

Redox Rep. 2023 Dec;28(1):2241615. doi: 10.1080/13510002.2023.2241615.

Abstract

Fecal microbiota is a significant factor determining the cause, course, and prognosis of Crohn's disease (CD). However, the factors affecting mucosa-associated microbiota (MAM) remain unclear. This retrospective study examined the differences in ileal MAM between CD patients and healthy controls and investigated the factors affecting MAM in CD patients to clarify potential therapeutic targets. Ileal MAM was obtained using brush forceps during endoscopic examination from 23 healthy controls and 32 CD patients (most were in remission). The samples' microbiota was profiled using the Illumina MiSeq platform. Compared to controls, CD patients had significantly reduced α-diversity in the ileum and a difference in β-diversity. The abundance of butyric acid-producing bacteria in the ileal MAM was significantly lower in CD patients with a history of abdominal surgery than in those without. Because butyric acid is a major energy source in the intestinal epithelium, its metabolism via β-oxidation increases oxygen consumption in epithelial cells, reducing oxygen concentration in the intestinal lumen and increasing the abundance of obligate anaerobic bacteria. The suppression of obligate anaerobes in CD patients caused an overgrowth of facultative anaerobes. Summarily, reducing the abundance of butyric acid-producing bacteria in the ileal MAM may play an important role in CD pathophysiology.

Keywords: Crohn’s disease; Inflammatory bowel disease; abdominal surgery; butyric acid-producing bacteria; intestinal dysbiosis; mucosa-associated microbiota; oxygen; terminal ileum.

MeSH terms

  • Bacteria
  • Butyric Acid / therapeutic use
  • Crohn Disease* / drug therapy
  • Crohn Disease* / microbiology
  • Crohn Disease* / surgery
  • Gastrointestinal Microbiome*
  • Humans
  • Ileum / microbiology
  • Ileum / surgery
  • Intestinal Mucosa
  • Microbiota*
  • Retrospective Studies

Substances

  • Butyric Acid

Grants and funding

This work was supported by Japan Society for the Promotion of Science: [Grant Number Grant Number 22K06758]; MAFF Commissioned project study on “Project for the realization of foods and dietary habits to extend healthy life expectancy”: [Grant Number Grant Number JPJ009842]; Research Project Grant of Kawasaki Medical School: [Grant Number R03B-052].