Short-chain fatty acids are associated with adiposity, energy and glucose homeostasis among different metabolic phenotypes in the Nutritionists’ Health Study

Abstract

Purpose: The gut microbiome is associated with obesity, mainly mediated by bacteria-produced short-chain fatty acids (SCFAs). It is unknown how SCFA concentrations are associated among the phenotypes metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese/overweight (MHO), and metabolically unhealthy obese/overweight (MUO). We compared plasma and fecal SCFA concentrations among adult women categorized according to the metabolic phenotypes mentioned above and examined associations between SCFA and adiposity and components of energy and glucose homeostasis.Methods: This was a cross-sectional study involving 111 participants. Body composition was assessed by DEXA. Energy and glycemic homeostasis were assessed by the standard mixed-meal tolerance test coupled with indirect calorimetry. SCFAs were quanti ed by gas chromatography and mass spectrometry. Results: Only plasma propionate was increased in the MHNW phenotype compared to the MHO and MUO phenotypes [p<0.05]. Fecal propionate and butyrate concentrations and plasma propionate concentrations were inversely associated with total and visceral adiposity [p<0.05]. Fecal and plasma SCFA concentrations were associated with reduced glucose, insulin, and HbA1c levels, increased fasting and postprandial GLP-1 levels and more preserved beta-cell function [p<0.05]. Fecal and plasma SCFA concentrations were positively correlated with resting energy expenditure and lipid oxidation rate and inversely correlated with oxidation rate of carbohydrates [p<0.05].Conclusion: These ndings reinforce the concept that fecal and plasma SCFA concentrations are linked to speci c components of energy and glucose homeostasis and body adiposity. On the other hand, it was not possible to discriminate the different metabolic phenotypes of adiposity based on the determination of fecal SCFA concentration.

Advances in fecal microbiota transplantation for the treatment of diabetes mellitus

“…Propionic acid regulates gluconeogenesis via GPR41 and affects glucose metabolism. Butyrate stimulates the secretion of GLP-1 by activating peroxisome proliferator-activated receptor γ (PPARγ) and increases the number and activity of regulatory T-lymphocytes by inhibiting the recruitment of neutrophils and effector T-cells, ultimately reducing inflammation and enhance insulin sensitivity ( He et al., 2020 ; Palmnäs-Bédard et al., 2022 ; Portincasa et al., 2022 ; Solar et al., 2023 ). Butyrate and acetate supplementation protects nonobese diabetic (NOD) mice from developing autoimmune diabetes ( Mariño et al., 2017 ).…”