Epithelial Response to Butyrate Diminished in Active IBD

By Reuters Staff

July 19, 2019

NEW YORK (Reuters Health) - The epithelial response to butyrate in patients with inflammatory bowel disease (IBD) is diminished, but only in the presence of tumor necrosis factor alpha (TNFalpha), researchers from Spain report.

The epithelial cell compartment appears to play a role in driving IBD, and some studies have shown a reduced capacity for butyrate synthesis, suggesting a possible role for butyrate supplementation as a therapeutic strategy.

Dr. Azucena Salas from IDIBAPS, Hospital Clinic, CIBERehd, in Barcelona, and colleagues used human primary epithelial organoid cultures (EpOCs) to test the effects of butyrate on healthy and IBD-affected intestinal epithelium.

The stool content of butyrate-producing bacteria was lower in patients with active IBD than in controls, but this did not correlate with decreased butyrate concentrations.

In healthy human EpOCs, butyrate significantly decreased the expression of proliferation markers and inflammatory markers and upregulated genes associated with defense against oxidative stress. The butyrate response in IBD-derived differentiated EpOCs was comparable to that of controls.

In contrast, active inflammation in IBD patients was associated with alterations in the expression of proteins involved in epithelial butyrate transport and metabolism, the researchers report in Inflammatory Bowel Diseases, online June 18.

The addition of TNFalpha to differentiated EpOCs (to mimic active IBD) reduced their ability to uptake and metabolize butyrate, although they continued to respond to short-chain fatty acids (SCFA), which promote an antioxidative, antimicrobial and overall protective response.

"We provide evidence that response to butyrate is not intrinsically altered in IBD patients under quiescent conditions, which thus supports the beneficial effects of butyrate in the absence of inflammation," the researchers conclude. "Nonetheless, as the downregulation of butyrate transporters and enzymes is associated with both active ulcerative colitis and Crohn's disease patients, supplementation of active patients with butyrate or SCFA extracts may not provide any beneficial effects as long as inflammation persists."

Dr. Salas did not respond to a request for comments.

SOURCE: https://bit.ly/2FKIoE9

Inflamm Bowel Dis 2019.