Abstract
BackgroundRecent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.DesignTwenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.ResultsConsumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.ConclusionsIn this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.
Highlights
With the continuous rise in obesity prevalence (NCD Risk Factor Collaboration, 2016a), the number of obese adults with metabolic syndrome and type 2 diabetes mellitus (DM2) has quadrupled over the last decade (NCD Risk Factor Collaboration, 2016b)
There were no significant differences in baseline characteristics between subjects who later received an autologous or allogeneic fecal microbiota transplantation (FMT) (Table 1)
We found a significant reduction in the fasting blood glucose level [from 5.8 (5.5–6.4) to 5.6 mmol/L (5.3–6.2), p = 0.02], a numeric, but non-significant, decrease in the fasting insulin levels [from 102 (62–124) to 83 (57–107), p = 0.25], and a borderline significant decrease in homeostatic model assessment of insulin resistance (HOMA-IR) [from 3.7 (2.3–4.6) to 2.8 (2.2–3.8), p = 0.056]
Summary
With the continuous rise in obesity prevalence (NCD Risk Factor Collaboration, 2016a), the number of obese adults with metabolic syndrome and type 2 diabetes mellitus (DM2) has quadrupled over the last decade (NCD Risk Factor Collaboration, 2016b). We have previously shown that transplantation of lean donor fecal microbiota can transiently improve insulin sensitivity in obese subjects with metabolic syndrome (Vrieze et al, 2012; Kootte et al, 2017). Mediterranean diet was associated with alterations in specific fecal bacterial species including an increase in the levels of A. muciniphila This well-studied bacterial species has previously been linked with improved glucose and cholesterol metabolism (Dao et al, 2016; Depommier et al, 2019) as well as healthy and Mediterranean diets (Liu et al, 2019; Rinott et al, 2020). Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome
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