A type 4 resistant potato starch alters the cecal microbiome, gene expression and resistance to colitis in mice fed a Western diet based on NHANES data

Four major types of resistant starch (RS1-4) are present in foods and can be fermented to produce short-chain fatty acids (SCFAs), alter the microbiome and modulate post-prandial glucose metabolism. While studies in rodents have examined the effects of RS4 consumption on the microbiome, fewer have examined its effect on gene expression in the cecum or colon or resistance to bacterial-induced colitis, and those that have, use diets that do not reflect what is typically consumed by humans. Here we fed mice a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data for 6-7 weeks and then supplemented their diet with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch. After three weeks, mice were infected with <i>Citrobacter rodentium</i> (<i>Cr</i>) to induce colitis. Infected mice fed the 10% VF diet had the highest levels of <i>Cr</i> fecal excretion at days 4, 7 and 11 post-infection. Infected mice fed the 5% and 10%VF diets had increased hyperplasia and colonic damage compared with the control. Changes in bacterial genera relative abundance, and alpha and beta diversity due to diet were most evident in mice fed 10% VF. <i>Cr</i> infection also resulted in specific changes to the microbiome and gene expression both in the cecum and the colon compared with diet alone, including the expression of multiple antimicrobial genes, <i>Reg3b</i>, <i>Reg3g</i>, <i>NOS2</i> and <i>Ifng</i>. These results demonstrate that VF, a RS4, alters cecal and colonic gene expression, the microbiome composition and resistance to bacterial-induced colitis.