Elucidating the Effect of Dietary Stearic Acid on the Regional Heterogeneity of the Gut Microbiome and Metabolome: Focus on Bile Acid Metabolism (SAMPill Study)

Stearic acid (18:0) is unique among saturated fatty acids (SFAs) as it does not increase cardiovascular disease (CVD) risk. Prior work by the study investigators suggests that gut microbiome-mediated alterations in secondary bile acid (BA) metabolism as a potential mechanism for the cholesterol-lowering effects of 18:0. However, to test this hypothesis the investigators were limited to traditional fecal sampling methods, which primarily reflect colonic microbes and do not capture regional heterogeneity in microbial communities or BA transformations which occur mainly in the small intestine. Using a novel ingestible device (mini-pill) which provides real-time sampling of the gastrointestinal environment, this study aims to comprehensively investigate the impact of dietary 18:0 on gut microbial BA transformations in modulating cardiometabolic risk. The study design includes a controlled 38-day dietary intervention trial in post-menopausal females using whole-foods enriched in commercially available sources of 18:0. The objectives are to determine the effect of dietary 18:0 on (i) microbiome composition and BA related functional pathways along the GI tract relative to stool; (ii) BA profiles along the GI tract, in stool and plasma; and (iii) FXR activation (reflected by FGF19 levels) and endogenous cholesterol synthesis in mediating the association between BA metabolizing microbes and BA profiles on CVD risk factors. Fecal whole-genome shotgun sequencing, targeted BA profiling, and bioinformatics will be used to address these objectives. Results will contribute to optimizing dietary/nutrient-labeling guidance to reduce CVD risk by expanding the evidence-base for classifying 18:0 and may offer novel strategies for preventing heart disease by targeting specific gut microbes or BA pathways.

Inclusion criteria

• Postmenopausal women (defined as complete natural cessation of menses for >12 months or a bilateral oophorectomy), who are not currently using hormone replacement therapy (HRT) or gender-affirming hormone treatments
• Age >50 years
• BMI >20 to <35 kg/m2, inclusive
• Non-smoker or former smoker who quit > 6 months
• Normotensive with or without medication
• Normal gastrointestinal function with regular bowel movements at least once every other day
• Willingness to swallow the mini-pills
• Willingness to collect and return multiple stool samples
• Adequate refrigerator and freezer space to store study meals
• Intent to remain in the greater Boston area during the intervention periods

Exclusion criteria

• Allergy/intolerance/religious reasons to avoid study meals or food ingredients
• Regular use of dietary supplements, pre/probiotics, laxatives or fiber supplements (except multivitamins) within the past 3 months
• Use of steroids (excluding topical) within the past 3 months
• Regular use of aspirin (except baby aspirin), NSAIDS, or anti diarrheal medication
• Current smokers or former smokers who quit < 6 months ago, and use of nicotine replacement products within the last 6 months
• Chronic constipation
• Use of oral antibiotics within the past 3 months.
• Use of dental prophylaxis within the past 3 months
• Regular use of stomach acid lowering and weight loss medications such as GLP-1 agonists
• Planned colonoscopy 3 months prior to or during the study period
• Swallowing disorder or inability or difficulty taking pills
• Malabsorptive and inflammatory bowel disease, diverticulosis, and history of diverticulitis, gastric esophageal/intestinal surgery, including lap banding or bariatric surgery.
• History of bowel obstruction, gallstones, gastroparesis, pancreas and liver/gallbaldder disorders.
• Any form of active substance abuse or dependence (including drug or alcohol abuse).
• Established major chronic diseases such as CVD, diabetes, active cancer within the last 5 years, or any significant medical condition at the study MD's discretion
• A clinical condition that, in the judgment of the study MD or PI, could potentially pose a health risk to the subject while involved in the study.
• Unwillingness to adhere to study protocol
• Intent to increase or decrease body weight during the study period
• No Social Security number (for payment and IRS forms).
• Individuals who directly report to any member of the research team.