Resistant potato starch alters the cecal microbiome and gene expression in mice fed a Western diet based on NHANES data

Authors: Smith, Allen; Chen, Celine; Cheung, Lumei; WARD, ROBERT - Utah State University; HEINTZ, KORRY - Utah State University; Dawson, Harry

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/26/2022
Publication Date: 3/22/2022
Citation: Smith, A.D., Chen, C.T., Cheung, L., Ward, R., Hintze, K., Dawson, H.D. 2022. Resistant potato starch alters the cecal microbiome and gene expression in mice fed a Western diet based on NHANES data. Frontiers in Nutrition. 9. Article 782667. https://doi.org/10.3389/fnut.2022.782667.
DOI: https://doi.org/10.3389/fnut.2022.782667

Interpretive Summary: Resistant starches (RS) are found in foods and are digested in the cecum and colon to produce compounds called short-chain fatty acids that may contribute to gut health. RS can also change the microbiome (kinds of bacteria found in the intestines) and how the digestive system functions. We fed mice a Total Western Diet (TWD), based on NHANES data obtained by surveying what kinds of food people eat, that mimics an American diet, for six weeks, and then supplemented the diet with 0, 2, 5, or 10% of a type of starch found in potatoes called resistant potato starch (RPS), for an additional three weeks. We then used a method called 16S sequencing that can tell us what types of bacteria are in the cecum of mice fed the different diets. We found that feeding mice RPS decreased the number of different kinds of bacteria in the cecum. Based on these changes to the microbiome, the mice could be divided into four groups depending on how much RPS they ate. Feeding the mice RPS caused some types of bacteria to increase and others to decrease. We found that the amount of a bacteria called Lachnospiraceae NK4A136 group increased to high levels in mice fed RPS. We also looked to see if feeding RPS changed the expression of certain genes important to how the cecum and colon work. he pattern of gene expression observed suggest that RPS primes the intestine for immune responses to bacteria, parasites and viruses. In the cecum we found that the number of changes we saw was dependent on the amount of RPS eaten and this was less so in the colon. The number of gene expression changes due to eating RPS was highest in the cecum and less so in different parts of the colon. We also found that the genes that changed in the cecum were different than the genes that changed in different parts of the colon. In summary, feeding RPS to mice caused large changes to the microbiome and gene expression in the cecum and to a smaller amount in the colon.

Technical Abstract: An abundant literature indicates that the four major types of resistant starch (RS1-4) are fermented in the cecum and colon to produce short-chain fatty acids and can alter the microbiome and host physiology. However, nearly all these studies were conducted in rodents fed a diet that does not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD), based on NHANES data that mimics the macro and micronutrient composition of a typical American diet, for six weeks, and then supplemented with 0, 2, 5, or 10% of the RS2, resistant potato starch (RPS), for an additional three weeks. The cecal microbiome was analyzed by 16S sequencing. The alpha-diversity of the microbiome decreased with increasing consumption of RPS while a beta-diversity plot showed four discreet groupings based on the RPS level in the diet. The relative abundance of various genera was altered by feeding increasing levels of RPS. In particular, the genus Lachnospiraceae NK4A136 group was markedly increased. Cecal, proximal and distal colon tissue mRNA abundance was analyzed by RNASeq. The cecal mRNA abundance principal component analysis showed clear segregation of the four dietary groups whose separation decreased in the proximal and further so in the distal colon. Differential expression of the genes was highest in the cecum but decreased substantially in the proximal colon and further so in the distal colon. Most differentially expressed genes were unique to each tissue with little overlap between tissues. The pattern of gene expression observed suggest that RPS primes the intestine for immune responses to bacteria, parasites and viruses. In summary, consumption of dietary RPS led to significant changes to the microbiome and gene expression in the cecum and to a lesser extent in the proximal and distal colon.