The new research, published in Journal of Biological Chemistry, used a mouse model of colitis to assess the potential benefits of five novel gut microbial metabolites after previous research on microbial metabolites of polyunsaturated fatty acids suggested they may have a variety of physiological benefits.
Led by senior researcher Professor Soichi Tanabe from Hiroshima University, Japan, the team found that that 10-hydroxy-cis-12-octadecenoic acid (HYA), a gut microbial metabolite of linoleic acid, has a suppressive effect on intestinal inflammation.
Tanabe and his team suggested that the findings show potential for HYA to be used as a functional food, adding that IBDs – including Crohn disease and ulcerative colitis – affect more than 4 million people globally.
According to Tanabe and his team, HYA was found to suppress TNF-alpha and dextran sulfate sodium-induced changes in the expression of tight junction-related molecules, occludin, zonula occludens-1, and myosin light chain kinase.
Dysfunction of tight junction (TJ) in the intestine is known to contribute to the pathogenesis of a variety of disorders including IBDs, said the team.
“HYA also suppressed the expression of TNF receptor 2 (TNFR2) mRNA and protein expression in Caco-2 cells and colonic tissue. In addition, HYA suppressed the protein expression of TNFR2 in murine intestinal epithelial cells,” said the authors.
Furthermore, Tanabe and his colleagues found that HYA significantly up-regulated G protein-coupled receptor (GPR) 40 expression in Caco-2 cells, and induced [Ca2+]i responses in HEK293 cells expressing human GPR40 with higher sensitivity than its metabolic precursor linoleic acid.
“Therefore, HYA modulates TNFR2 expression, at least partially, via the GPR40-MEK-ERK pathway and may be useful in the treatment of TJ-related disorders such as inflammatory bowel disease,” suggested the team.
Source: Journal of Biological Chemistry
Published online ahead of print, doi: 10.1074/jbc.M114.610733
"A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway"
Authors: Junki Miyamoto, et al