Objective: To examine the associations of fecal bile acid (BAs), interacting with the Mediterranean diet (MedDiet), with body adiposity and lipid biomarkers and explore the gut microbiome’s role in BA metabolism.
Method: In the 18-month DIRECT-PLUS Trial, 284 participants (mean 51 y, 88% men) were randomized to one of the three isocaloric interventions: healthy dietary guidelines, MedDiet, and MedDiet+polyphenols and measured for baseline fecal BA levels by LC-MS. Their gut microbiomes were profiled by shotgun metagenomics.
Results: Among 39 detected BAs, 4 were associated with body mass index (BMI) and 11 were associated with serum lipids (Fig. 1A). For example, per 1-SD increment in isoursodeoxycholic acid-sulfate level was associated with a 3.0 kg/m2 increase in BMI (95% confidence interval [CI]: 1.8-4.2) and 12.5 mg/dL increase in triglycerides (95% CI: 5.4-19.7). The MedDiet’s effects for reducing BMI varied by BA levels (Fig. 1B). For example, this effect was more pronounced in those with lower 12-dehydrocholic acid levels (qinter=0.004). We identified several Ruminococcus spp. as major BA metabolizers and their role in modifying fecal BAs’ association with body adiposity and lipid levels (Fig. 1C-D).
Conclusion: The gut microbial metabolism of BAs is associated with host adiposity and lipid profiles and potentially modifies the beneficial effects of MedDiet on cardiometabolic health.
P. Gao: None. Z. Mei: None. F. Wang: None. D. Dong: None. M. Stampfer: Advisory Panel; Elysium Health. I. Shai: None. D. Wang: None.
National Institutes of Health (R00DK119412, R01NR01999, and R01AG077489)
