Fermentable fibers upregulate suppressor of cytokine signaling1 in the colon of mice and intestinal Caco-2 cells through butyrate production

Abstract

Short chain fatty acids (SCFAs), the microbial metabolites of fermentable dietary fibers exert multiple beneficial effects on mammals including humans. We examined the effects of fermentable dietary fibers on suppressor of cytokine signaling 1 (SOCS1), a negative regulator of inflammatory signaling, on the intestinal epithelial cells of the mouse colon and human intestinal Caco-2 cells, specifically focusing on the role of SCFAs. Feeding fermentable fibers, guar gum (GG) and partially hydrolyzed GG (PHGG) increased SOCS1 expression in the colon and the cecal pool of some SCFAs including acetate, propionate, and butyrate. The antibiotic administration abolished the GG-mediated SOCS1 expression in the colon. In Caco-2 cells, butyrate, but not other SCFAs, increased SOCS1 expression. Taken together, fermentable fibers such as GG and PHGG upregulate the colonic SOCS1 expression, possibly through the increased production of butyrate in mice and can be a potential tool in the fight against inflammatory diseases. Abbreviations: GG: Guar gum; GPR: G protein-coupled receptor; IL: Interleukin; JAK: Janus kinase; NF- κB: Nuclear factor-kappa B; PHGG: Partially hydrolyzed guar gum; SCFA: Short chain fatty acid; SOCS: Suppressor of cytokine signaling; STAT: Signal transducer and activator of transcription; TLR: Toll-like receptor.

Propionate and Dietary Fermentable Fibers Upregulate Intestinal Heat Shock protein70 in Intestinal Caco-2 Cells and Mouse Colon

“…Whole protein extracts of Caco-2 cells and mouse colonic epithelial cells were prepared as described previously. 16 Proteins (20 μg) were separated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and then transferred to polyvinylidene difluoride membranes. The membranes blocked with 5% skimmed milk were blotted for HSP70, phospho-ERK1/2, total ERK1/ 2, phospho-mTOR, total mTOR, phospho-HSF1, total HSF1, and βactin using specific antibodies in combination with HRP-conjugated anti-rabbit and -mouse IgG antibodies.…”

“…Human intestinal Caco-2 cells (American Type Culture Collection, Manassas, VA) were propagated and maintained as described previously. , All experiments, except for luciferase assay, were conducted on day 14 after seeding when cells reached confluence and were fully differentiated.…”

“…Acetate, propionate, and butyrate are the major SCFAs present at high concentrations in the intestinal lumen. Our previous studies demonstrated that a water-soluble, fermentable guar gum (GG) fiber diet increased luminal SCFAs in mice. − A significant body of evidence from clinical and basic research has reported the essential roles of SCFAs in regulating intestinal homeostasis . In particular, butyrate has attracted more attention than other SCFAs.…”

Effects of alkaloid-rich extracts obtained from Grifola frondosa on gut microbiota and glucose homeostasis in rats

“…Short chain fatty acids secreted by microbiota increased Socs1 expression, which implied the possibility of microflora regulating liver. 62 Other metabolites, such as oxyberberine and equol, were selected as potential molecule to regulate PI3K in liver. 63,64 These results agreed with our results.…”

Dietary Control of Inflammation and Resolution

“…Gut bacteria require the dietary intake of fermentable fiber to generate short-chain fatty acids (SCFA). SCFA act as signaling agents to maintain the gut barrier's integrity by decreasing inflammation in the gut wall (94,95).…”