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

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.

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study

“…Faecalibacterium prausnitzii (LDA score = 2.91, p = 0.0005) presented the highest discriminant power in the NT group. This specie and Roseburia hominis (LDA score = 2.76, p = 0.02), both biomarkers for NT, have been described as the main SCFA-producers in healthy status 15,25 . Several species of the Ruminococcaceae genera were also enriched in the NT group (s127, s458, s408, s899).…”

“…(2018) 15 examined in 441 subjects associations of fecal SCFA, gut microbiota and cardiometabolic outcomes, and they observed that higher fecal SCFA concentrations were associated with a measure of gut permeability and hypertension.…”

“…Studies are conflicting as to whether SCFA are beneficial or detrimental to cardiometabolic health. In a recent study de la Cuesta-Zuluaga et al (2018) 15 reported in a human cohort that higher fecal SCFA concentrations were associated with a measure of gut permeability and also hypertension. The same authors also highlighted that more studies are needed analyzing both fecal and circulating SCFA in humans to test the hypothesis that the association of higher fecal SCFA with cardiometabolic dysregulation is due to less efficient SCFA absorption to circulation.…”

Role of short-chain fatty acids in the gut-brain axis in schizophrenia: contribution to immune activation and pathophysiology in humans and mice

“…This conclusion is based on two lines of evidence from human and animal, respectively. Although SCFAs are generally regarded as beneficial microbial metabolites for human health, our results, together with several lines of evidence [47, 48, 49, 50] indicate that, like a double-edge sword, excessive SCFA beyond physiological concentration can interfere with biological functioning of host. To the best of our knowledge, this is the first study to show that higher fecal SCFA excretion and circulating SCFA are presented in schizophrenia.…”

“…To the best of our knowledge, this is the first study to show that higher fecal SCFA excretion and circulating SCFA are presented in schizophrenia. Generally, circulating SCFAs may better represent SCFA production and absorption[50]. Increased SCFA in both circulation and feces of patients with schizophrenia suggests that SCFA production by microbiota is too excessive in gut to be decreased to normal level by increasing absorption.…”