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. 16(9):3439-3464. https://doi.org/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 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 Citrobacter rodentium (Cr) to induce colitis. Infected mice fed the 10% VF diet had the highest levels of Cr 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. Cr 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, 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.