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

Authors: Pletsch, Elizabeth; Dawson, Harry; Cheung, Lumei; Ragonese, Jack; Chen, Celine; Smith, Allen

Submitted to: Food and Function
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2025
Publication Date: 4/10/2025
Citation: Pletsch, E.A., Dawson, H.D., Cheung, L., Ragonese, J.S., Chen, C.T., Smith, A.D. 2025. 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. Food and Function. 10.1039/d4fo04697h.
DOI: https://doi.org/10.1039/d4fo04697h

Interpretive Summary: Dietary fiber is important for maintaining and improving digestive health, yet the daily recommended intake for dietary fiber is often not met by Americans consuming a Western diet. Resistant starches (RS) are a type of dietary fiber that resists digestion, and instead is fermented by bacteria in the large intestine to produce beneficial components, such as short chain fatty acids, which can be used by the body to control intestinal and metabolic functions. There are four types of RS, and type 4 RS (RS4) is a chemically modified starch that has become a popular ingredient used to increase fiber content in foods. We previously showed that feeding mice a RS4 made from potato induced changes in the gut microbiome and expression of genes in the intestine. Increased dietary fiber intake is associated with reduced risk of colitis and inflammation, possibly by changing the types of bacteria that live in the intestines. This study investigated the effect of feeding mice RS4 on their susceptibility to a bacterial infection. Mice were fed a Western-style diet for six weeks, followed by the Western-style diet supplemented with increasing levels of a RS4. After three weeks on the RS4 diets, mice were infected with Citrobacter rodentium (Cr), a mouse bacteria that causes colitis and is similar to Escherichia coli that can cause disease in people. At 12 days post-infection, samples were collected to see if consuming a RS4 changed the way the mice responded to the Cr infection. We found increased levels of Cr in the feces, greater changes in bacterial abundance and diversity, higher expression of inflammatory markers, and more damage to the intestine in mice fed the highest level of RS4, indicating that the mice had a more severe infection. These findings suggest that while there may be health benefits from incorporating RS into the diet as a source of dietary fiber, consuming certain levels of RS may also increase susceptibility to gastrointestinal bacterial infections.

Technical Abstract: Four major types of resistant starch (RS1-4) are present in foods, all of which can be fermented to produce a variety of compounds including short-chain fatty acids (SCFAs) and alter the microbiome. Type 4 RSs are chemically modified starches that have become a popular food additive to increase the fiber content. While studies in both humans and rodents have investigated the effect of different RS4 on post-prandial glucose metabolism, fewer studies have examined the effects of RS4 consumption on the microbiome or gene expression in the cecum or colon or resistance to bacterial-induced colitis. Furthermore, many rodent RS studies use high-fat 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 1490TM (VF), a phosphorylated and cross-linked potato starch, for an additional 3-4 weeks followed by infection with Citrobacter rodentium (Cr) to induce colitis. Mice fed the 10% VF diet had increased Cr fecal excretion at days 4, 7 and 11 post-infection. Increased hyperplasia and colonic damage was found in infected mice fed the 5% and 10% VF diets compared to mice fed the basal diet. The cecal contents were analyzed for microbiota composition. The alpha-diversity as measured by the Shannon Index decreased in mice fed the TWD with 10% VF 1490 and this was not altered by infection. Beta-diversity plots showed distinct effects due to diet and infection with the 5% and 10% VF groups showing the greatest changes. Similarly, the largest changes in relative abundance of various genera were greatest in mice fed the 10% VF diet. Cr infection also resulted in specific changes to the microbiome and gene expression both in the cecum and the colon. Diet alone induced fewer changes. The expression of multiple antimicrobial genes in the cecum and/or colon was increased in infected mice fed the 10% VF diet vs. the TWD diet including Reg3b, Reg3g, NOS2 and Ifng. These results demonstrate that VF, a RS4, alters cecal and colonic gene expression, the microbiome composition and resistance to bacterial-induced colitis.