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

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.

Citrus limon Peel Powder Reduces Intestinal Barrier Defects and Inflammation in a Colitic Murine Experimental Model.

This study examines the ameliorative effects of lemon (Citrus limon) peel (LP) powder on intestinal inflammation and barrier defects in dextran sulfate sodium (DSS)-induced colitic mice. The whole LP powder was fractionated into methanol (MetOH) extract and its extraction residue (MetOH residue), which were rich in polyphenolic compounds and dietary fibers, respectively. Mice were fed diets containing whole LP powder, MetOH extract, and MetOH residue for 16 d. DSS administration for 9 d induced bodyweight loss, reduced colon length, reduced the colonic expression of tight junction proteins including zonula occludens-1 and -2, and claudin-3 and -7, and upregulated colonic mRNA expression of interleukin 6, chemokine (C-X-C motif) ligand 2, and C-C motif chemokine ligand 2. Feeding LP powder restored these abnormalities, and the MetOH residue, but not MetOH extract, also showed similar restorations. Feeding LP powder and MetOH residue increased fecal concentrations of acetate and n-butyrate. Taken together, LP powder reduced intestinal damage through the protection of tight junction barriers and suppressed an inflammatory reaction in colitic mice. These results suggest that acetate and n-butyrate produced from the microbial metabolism of dietary fibers in LP powder contributed to reducing colitis.

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

Short-chain fatty acids (SCFAs), including propionate, are major metabolites of intestinal microorganisms and play an essential role in regulating intestinal epithelial integrity. Heat shock proteins (HSPs) promote cellular homeostasis under physiological and stressed conditions. This study aimed to investigate the regulation of intestinal HSP70 by propionate in human intestinal Caco-2 cells and the colon of fermentable dietary fiber (DF)-fed mice and germ-free mice. The results showed that propionate increased Hspa1a (HSP70 mRNA) level in Caco-2 cells, upregulated HSP70 protein, and phosphorylation of heat shock factor 1; however, the latter two were reduced by mitogen-activated protein kinases and the mechanistic target of rapamycin inhibitors. Feeding fermentable DFs, such as guar gum (GG) and partially hydrolyzed GG, increased both cecal SCFAs and colonic HSP70 expression, both of which were reduced in germ-free mice than in specific-pathogen-free mice. Collectively, the propionate-induced HSP70 expression was shown to be possibly involved in intestinal homeostasis.