Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors.

Jacobo De La Cuesta-Zuluaga,Noel Mueller,Jenny Carmona,Eliana Velásquez-Mejía,Vanessa Corrales-Agudelo,José Abad,Juan Escobar,Jelver Sierra,Rafael Álvarez-Quintero

doi:10.3390/nu11010051

Jacobo De La Cuesta-Zuluaga, Noel Mueller + Show 7 more

Open Access

https://doi.org/10.3390/nu11010051

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Abstract

Fiber fermentation by gut microbiota yields short-chain fatty acids (SCFAs) that are either absorbed by the gut or excreted in feces. Studies are conflicting as to whether SCFAs are beneficial or detrimental to cardiometabolic health, and how gut microbiota associated with SCFAs is unclear. In this study of 441 community-dwelling adults, we examined associations of fecal SCFAs, gut microbiota diversity and composition, gut permeability, and cardiometabolic outcomes, including obesity and hypertension. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. Fecal SCFA concentrations were inversely associated with microbiota diversity, and 70 unique microbial taxa were differentially associated with at least one SCFA (acetate, butyrate or propionate). Higher SCFA concentrations were associated with a measure of gut permeability, markers of metabolic dysregulation, obesity and hypertension. Microbial diversity showed association with these outcomes in the opposite direction. Associations were significant after adjusting for measured confounders. In conclusion, higher SCFA excretion was associated with evidence of gut dysbiosis, gut permeability, excess adiposity, and cardiometabolic risk factors. Studies assessing both fecal and circulating SCFAs are needed to test the hypothesis that the association of higher fecal SCFAs with obesity and cardiometabolic dysregulation is due to less efficient SCFA absorption.

Highlights

One of the main functions of the human intestinal microbiota is to ferment indigestible dietary fiber in the large intestine
For the 212 males and 229 females enrolled in our study, we found that participants with higher fecal butyrate excretion were more likely to be male (q = 0.03), to consume more dietary fiber (q = 0.03)
We found that the inverse association between fecal butyrate and gut microbiota diversity persisted after adjustment for confounders (q < 0.0001; Figure 1, Table 2, and Figure S1)

Summary

Introduction

One of the main functions of the human intestinal microbiota is to ferment indigestible dietary fiber in the large intestine. The products of this fermentation process are short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate [1]. SCFAs can either be excreted in the feces or taken up by the gut epithelium to participate in a variety of physiologic processes. Uptake of SCFAs involves poorly selective anion-transporting proteins expressed by the gut epithelium, whose purpose is to maximize the amount of SCFAs absorbed from the lumen [2]. In particular, serves as the primary energy source for colonocytes [3]. Other molecules enter the portal circulation where they can be metabolized by the liver, or released into the systemic circulation where they can bind to SCFA receptors in the vascular epithelium or afferent arterioles and alter cardiometabolic health [4]

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