Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial.

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• This RCT identified a correlation between gut microbiome and secondary bile acid in relation to Mediterranean diet interventions.

• Fourteen specific faecal bile acids were associated with higher BMI and triglyceride levels.

• A Mediterranean diet is reported to have a positive effect on BMI and triglycerides, however these results may be influenced by an individual’s gut microbial bile acid metabolism.

Introduction:

A randomised control trial was conducted to investigate the effect of microbiome metabolism of bile acids (BA) of the Mediterranean diet in patients with a high metabolic risk.

Method:
A total of 284 participants (88% male; range as 31.9 to 82.0 years; mean BMI of 31 kg/m², SD 3.9) were randomised into three groups: a healthy guideline group, calorie-restricted Mediterranean diet plus 28g walnuts (MedDiet), and a MedDiet group including 3-4 cups green tea. Faecal bile acids (BAs), microbiome sequencing and serum lipids were assessed at baseline, 6 months, and 18 months.

Results:

• The MedDiet interventions improved BMI (p<0.001), triglycerides (p=0.046), and TC/HDLc ratio (p<0.01) over 18 months compared to the HDG group;

•The BMI-lowering effect of the MedDiet was more pronounced in participants with lower baseline 12-dehydrocholic acid (12-DHCA) (q<0.001) taurocholic acid (TCA) (q=0.003), taurolithocholic acid 3-sulfate (TLCA-S) (q=0.009) and glycocholenoic-sulfate (GCOA-S)(q<0.001) than the HDG group;

•Compared with the HDG group,the MedDiet interventions resulted in a larger reduction in certain fecal bile acids (p<0.05);

• Furthermore, the study reported a significant correlation between the abundance and microbial species of the gut microbiome and the secondary bile acid (BA) pool across all participants (p= 0.001);

• Higher concentrations of specific BA species families were positively associated with increased triglycerides levels and TC/HDLc ratios across all participants (p=0.001).

Conclusion:

This RCT demonstrates that Mediterranean diet interventions have an effect on BMI and lipid markers and that these results may differ depending on an individual's baseline fecal profile. Overall the findings highlight the importance of gut microbial bile acid metabolism in shaping personalised responses to dietary interventions.

• This study demonstrates that gut microbiome diversity influences the composition of the secondary bile acids.

• Elevated levels of bile acids were reported to be associated with higher BMI, while UDCA, HCA and LCA were associated with high-density lipoprotein (HDLc) levels.

• Healthcare practitioners may therefore consider assessing a patient's faecal microbiome and bile acid profiles to better understand an individual's response to a recommended dietary intervention.

• These findings may encourage practitioners to consider the Mediterranean diet to optimise the gut microbiome and support bile acid metabolism.

• This study was limited in that the study population comprised largely males (88%). Future research is needed to include more diverse populations.

• Further in-depth studies are also required to investigate the mechanism through which bile acids influence metabolic health.