Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth

Abstract

Objective: We aimed at determining the relationship of the gut microbiota and short chain fatty acids with obesity and fat partitioning and at testing potential differences in the ability of gut microbiota to ferment equal amounts of carbohydrates (CHO) between lean and obese youth.

Research design and methods: We analyzed the gut microbiota of 84 youth in whom body fat distribution was measured by fast-magnetic resonance imaging, de novo lipogenesis (DNL) quantitated using deuterated water, and the capability of gut flora to ferment CHO was assessed by ¹³C-fructose treatment in vitro.

Results: A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and SC fat (all P < .05). Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat (all P < .05) and with hepatic DNL (P = .01, P = .09, P = .04, respectively). Moreover, the rate of CHO fermentation from the gut flora was higher in obese than in lean subjects (P = .018).

Conclusions: These data demonstrate that obese youth show a different gut flora composition than lean and that short chain fatty acids are associated with body fat partitioning and DNL. Also, the gut microbiota of obese youth have a higher capability than the gut flora of lean to oxidize CHO.

Figure 1.

Distribution of abundant OTUs among samples. This heatmap shows the abundance (shades of gray) of common OTU with samples as rows and OTU as columns. The samples were clustered based on the entire community, not just the OTU shown in this figure. The blue bars on the sides of the heatmap indicate the BMI category of the subject, whereas the colored blocks along the top indicate the phyla that the OTU belongs to. Eighty-four subjects were included in the analysis.

Figure 2.

Association of plasma concentrations of SCFA with baseline BMI and changes of BMI over time. Association between SCFA and BMI for (A) acetate (r² = 0.11, P = .004) (B) propionate (r² = 0.25, P < .001), and (C) butyrate (r² = 0.23, P < .001) independent of age, gender, and ethnicity. Changes of BMI per year are positively correlated with plasma levels of (D) acetate (r² = 0.08, P = .0018), (E) propionate (r² = 0.158, P = .004), and (F) butyrate (r² = 0.083, P = .016), independent of age, gender, follow-up time, ethnicity, and baseline BMI. The SCFA are expressed in uM/L and changes of BMI over time are expressed as delta BMI/year. A general linear model was used to assess the studied associations and age, gender and ethnicity were used as covariates; 84 subjects were analyzed at baseline and 72 subjects were analyzed at follow-up.

Figure 3.

Relationship between SCFA and hepatic de novo lipogenesis and differences in gut flora capability to ferment carbohydrates between lean and obese. Plasma concentrations of (A) acetate were associated with fasting hepatic DNL (P = .01) and (B) the same trend was observed for propionate (P = .09), whereas (C) concentrations of butyrate were associated with delta increase of hepatic DNL (P = .04) after a carbohydrates load (75 g of glucose and 25 g of fructose). The DNL is expressed in percent and the SCFA are expressed in uM/L. A Spearman correlation was used to analyze the data (n = 14). (D) The gut flora of obese individuals have a higher ability to ferment carbohydrates (express as ¹³CO₂ derived from the ¹³C fructose) than the gut flora of lean subjects (P = .018). The production of ¹³CO₂ is expressed as parts per thousand in each 100:1 fecal sample. A Mann-Whitney test was used to analyze the data (n = 17).