No abstract

The gut microbiota plays an important role in cardio-metabolic diseases with diet being among the strongest modulators of gut microbiota composition and function. Resistant dietary carbohydrates are fermented to short-chain fatty acids (SCFAs) by the gut bacteria. Fiber and omega-3 rich diets increase SCFAs production and abundance of SCFA-producing bacteria. Likewise, SCFAs can improve gut barrier integrity, glucose, and lipid metabolism, regulate the immune system, the inflammatory response, and blood pressure. Therefore, targeting the gut microbiota with dietary strategies leading to increased SCFA production may benefit cardio-metabolic health. In this review, we provide an overview of the association between diet, SCFAs produced by the gut microbiota and cardio-metabolic diseases. We first discuss the association between the human gut microbiota and cardio-metabolic diseases, then investigate the role of SCFAs and finally explore the beneficial effects of specific dietary interventions that can improve cardio-metabolic outcomes through boosting the SCFA production.

BackgroundAcetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort.ResultsMicrobiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18], P = 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with Coprococcus, Barnesiella, Ruminococcus, and Ruminococcaceae NK4A21 and negative correlations were observed with Lachnoclostridium and Bacteroides. We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = −0.07 [−0.11, −0.04], P = 2.8 × 10–4) and between visceral fat and Lachnoclostridium (Beta [95%CI] = 0.076 [0.042, 0.11], P = 1.44 × 10–5). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect of Lachnoclostridium on visceral fat. The taxonomic diversity showed that Lachnoclostridium and Coprococcus comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that Coprococcus spp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol in Lachnoclostridium spp.ConclusionsOur data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat. Coprococcus may play an important role in host health by its production of vitamins B and SCFAs, whereas Lachnoclostridium might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.

The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions—Mediterranean (M) and high protein (HP)—improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M–HP or HP–M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = −6.98 (−12.30, −1.65) µIU/mL, p = 0.01; HOMA-IR: −1.78 (95% CI: −3.03, −0.52), p = 9 × 10−3); and (ii) improving glycemic variability (−3.13 (−4.60, −1.67) mg/dL, p = 4 × 10−4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.