Abstract

Epidemiological studies suggest a positive association between obesity and fecal short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary carbohydrates, while animal models suggest increased energy harvest through colonic SCFA production in obesity. However, there is a lack of human population-based studies with dietary intake data, plasma SCFAs, gut microbial, and anthropometric data. In 490 Chinese adults aged 30–68 years, we examined the associations between key plasma SCFAs (butyrate/isobutyrate, isovalerate, and valerate measured by non-targeted plasma metabolomics) with body mass index (BMI) using multivariable-adjusted linear regression. We then assessed whether overweight (BMI ≥ 24 kg/m2) modified the association between dietary-precursors of SCFAs (insoluble fiber, total carbohydrates, and high-fiber foods) with plasma SCFAs. In a sub-sample (n = 209) with gut metagenome data, we examined the association between gut microbial SCFA-producers with BMI. We found positive associations between butyrate/isobutyrate and BMI (p-value < 0.05). The associations between insoluble fiber and butyrate/isobutyrate differed by overweight (p-value < 0.10). There was no statistical evidence for an association between microbial SCFA-producers and BMI. In sum, plasma SCFAs were positively associated with BMI and that the colonic fermentation of fiber may differ for adults with versus without overweight.

Highlights

  • Overall and central obesity are major risk factors for a wide range of chronic diseases, including cardiometabolic diseases [1,2,3]

  • We first examined the associations between plasma short-chain fatty acids (SCFAs) and body mass index (BMI) and waist-to-height ratio (WHtR) and found that butyrate/isobutyrate was positively associated with BMI (p-value = 0.04) and WHtR (p-value = 0.003), and isovalerate (p-value = 0.04) and total SCFAs (p-value = 0.03) were positively associated with WHtR

  • We found no association between the total relative abundance (p-value > 0.05) of microbial SCFA producers with plasma SCFAs, a few specific species were associated with butyrate/isobutyrate, valerate, isovalerate, and/or total plasma SCFAs (Table S9) at p-value < 0.05, including Faecalibacterium prausnitzii

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Summary

Introduction

Overall and central obesity are major risk factors for a wide range of chronic diseases, including cardiometabolic diseases [1,2,3]. Recent evidence has shown that the gut microbiota and microbiota-mediated metabolites like short-chain fatty acids (SCFAs) influence diet-induced obesity [4,5]. SCFAs like butyrate are major products of microbiota fermentation of dietary carbohydrates, especially soluble fiber and resistant starch [4]. Fiber-rich diets and Mediterranean diets have been shown to be positively associated with weight loss [6,7] and increased serum [8] and fecal SCFAs [9], respectively. Studies have yielded incongruent results for the SCFA-obesity association, which involves various factors like diet and gut microbiota. Whereas several studies have demonstrated that dietary SCFA supplementation may be beneficial to weight loss through appetite regulation [10,11]

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