Plants contain soluble and insoluble fiber, the former of which undergoes fermentation by the gut microbiota in the large intestine. By-products of this fermentation are gasses and short-chain fatty acids (SCFA), including butyrate (BUT), propionate (PROP), and acetate (ACET). Dietary fiber has become an important tool in maintaining gut health. In particular, SCFA’s, especially butyrate, have been linked to colonic and whole body health including increased immunity, lower adiposity and lower blood pressure. SCFA’s also affect intestinal cell proliferation and apoptosis. Most in vitro work on SCFA’s has been in human cancer cell lines. Recent advances in technology which allow for culturing of primary intestinal cells (organoids) that recapitulate epithelial lineage development have allowed for a more physiologically relevant model. Our objective was to examine effects of SCFA on biomarkers of stem cell activity, differentiation, barrier function and epithelial defense in intestinal organoids. Organoids were treated with 5 mM BUT, iso-BUT, PROP, or ACET compared to untreated controls. Gene expression of intestinal stem cell marker, Lgr5 decreased 5-fold due to BUT and PROP but only 1.5-fold due to ISOBUT and increased 2-fold due to ACET treatment (P &lt; 0.05) indicating that ACET does not alter proliferation. Differentiated cell marker, Alpi was decreased 3-fold due to BUT, however increased two to five-fold due to ACET, ISOBUT, and PROP treatment (P &lt; 0.05) indicating an increase in cell differentiation. Mucus producing goblet cell marker, Muc2 was decreased more than 3-fold due BUT, ISOBUT and PROP treatment, but did not change due to ACET. Host microbial defense was also affected as Defb1, an epithelial anti-microbial peptide (AMP) was significantly increased due to all SCFA treatments (P &lt; 0.05). A second AMP, Reg3b was significantly elevated due to all treatments, especially BUT, ISOBUT, and PROP which were 300-500 fold higher than controls (P &lt; 0.05). Gene expression of tight junction (TJ) claudin-3 (Cldn3) was decreased 2-fold due to BUT and ISOBUT treatment but was not altered due to PROP and was increased 1.6-fold due to ACET (P &lt; 0.05). In conclusion, the organoid model recapitulates normal in vivo physiology and confirms previous in vitro SCFA data while providing new insight. Intestinal organoids serve as an excellent model to study nutritional compounds and human health and may help improve nutritional requirements in the future.

Effects of dietary fiber by-product short-chain fatty acids on intestinal cell physiology and health

256th National Meeting (2018)

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