Host genetic variation, sex, and dietary impacts on short-chain fatty acid utilization

 

Quantitative trait loci (QTL) linked to glucose homeostasis are associated with short-chain fatty acids (SCFAs) that are influenced by sex and/or diet. Interactions between host genetics, sex, and diet affect cecal and fecal SCFA levels. SCFA produced by bacteria could be linked to QTL which could suggest host genetics affects specific bacterial taxa responsible for SCFA levels that could ultimately affect glucose homeostasis.

Quantitative trait loci (QTL) linked to glucose homeostasis are associated with short-chain fatty acids (SCFAs) that are influenced by sex and/or diet. Interactions between host genetics, sex, and diet affect cecal and fecal SCFA levels. SCFA produced by bacteria could be linked to QTL which could suggest host genetics affects specific bacterial taxa responsible for SCFA levels that could ultimately affect glucose homeostasis.

My postdoctoral research at the University of Wisconsin-Madison explores host genetic variation, sex, and dietary interactions on the gut microbiome and short-chain fatty acid (SCFA) utilization. I conduct my research in Dr. Federico Rey’s lab group with collaboration with Dr. Alan Attie’s lab group. The objective of my research is to identify possible candidate genes QTLs associated with SCFAs that can be linked to physiologic traits.

My research involves the Diversity Outbred (DO) mice, which is a genetically-diverse population of mice that were derived from many generations of random interbreeding of eight genetically-distinct inbred mouse strains (DO Founders). The DO mice were fed a high-carbohydrate, low-fat (HC/LF) diet or high-fat, low-carbohydrate (HF/LC) diet with the same fiber content for gut microbes to use.

The distal gut as a major site of short-chain fatty acid production

The distal gut is a major location of short-chain fatty acid (SCFA) production with the fecal SCFAs being a proxy measurement of SCFA excretion. Gut microbes degrade fiber in the cecum (appendix in humans and functionally different) which leads to fermentation of carbohydrates that results in SCFAs being produced. SCFAs can be absorbed along the host’s colon and any unabsorbed SCFAs are excreted in the feces. Note: SCFAs are produced and absorbed in the entire intestine, but the cecum is the central location for breaking down fiber and high fermentation activity.

I quantify SCFAs using headspace gas-chromatography (HS-GC). By measuring cecal and fecal SCFAs, I can calculate the cecal/fecal ratio to estimate the potential amounts of SCFAs that can be taken up by the host.