Elucidating the Effect of Dietary Stearic Acid on the Regional Heterogeneity of the Gut Microbiome and Metabolome: Focus on Bile Acid Metabolism
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Relative Abundance of Gut Microbial Taxa (%)
研究概览
简要总结
Stearic acid and palmitic acid are two common consumed saturated fatty acids found in foods. Palmitic acid is associated with increases in blood cholesterol, whereas stearic acid is generally considered neutral with respect to blood cholesterol. However, the mechanisms underlying these different effects are not fully understood. The goal of this clinical trial is to determine how replacing dietary palmitic acid with stearic acid affects microorganisms living in the gastrointestinal tract (gut microbiome) and the metabolites they produce, including secondary bile acids, and whether these changes influence heart and metabolic health in postmenopausal women. The main question it aims to answer is whether the cholesterol lowering effect of dietary stearic acid, compared to dietary palmitic acid is due to changes in the composition and function of the gut microbiome and bile acid metabolism. Participants will consume a controlled diet high in palmitic acid for a 10-day run-in period, followed by a controlled diet high in stearic acid for 28 days. During the study, participants will provide biological samples, including blood samples collected in both fasting and non-fasting states, for assessment of cardiometabolic outcomes. Participants will also swallow mini-pills designed to collect samples from different regions of the gastrointestinal tract to assess the gut microbiome and related metabolites. Results will contribute to understanding the relationship between stearic acid mediated microbiota effects on cardiometabolic heath.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Palmitic Acid Run-In Followed by Stearic Acid Diet
A controlled 38-day intervention with a10 day run-in phase with a diet high in palmitic acid to stabilize baseline variables, followed by a 28 diet phase with a diet high in stearic acid
干预措施: High Palmitic Acid Diet (Other)
Palmitic Acid Run-In Followed by Stearic Acid Diet
A controlled 38-day intervention with a10 day run-in phase with a diet high in palmitic acid to stabilize baseline variables, followed by a 28 diet phase with a diet high in stearic acid
干预措施: High Stearic Acid Diet (Other)
结局指标
主要结局
Relative Abundance of Gut Microbial Taxa (%)
时间窗: End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.
Gut microbial composition in gastrointestinal luminal and stool samples will be assessed using whole-genome shotgun metagenomic sequencing and reported as relative abundance (%). Alpha and beta diversity will also be evaluated as part of the microbiome analyses.
Relative Abundance of Gut Microbial Functional Pathways (%)
时间窗: End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.
Gut microbial functional pathways in gastrointestinal luminal and stool samples will be assessed from whole-genome shotgun metagenomic sequencing data using bioinformatic pathway analysis and reported as relative abundance (%). Analyses will include pathways related to bile acid metabolism as well as other microbial metabolic pathways.
Concentrations of Bile Acids in Gastrointestinal Luminal Samples (nmol/mL)
时间窗: End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.
Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in gastrointestinal luminal samples using targeted mass spectrometry and reported as nmol/mL.
Concentrations of Bile Acids in Plasma (nmol/mL)
时间窗: End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.
Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in fasting and postprandial plasma using targeted mass spectrometry and reported as nmol/mL.
Concentrations of Bile Acids in Stool (nmol/mg dry weight)
时间窗: End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.
Primary and secondary bile acids, including conjugated and unconjugated bile acids, will be quantified in stool using targeted mass spectrometry, normalized to fecal dry weight, and reported as nmol/mg dry weight.
次要结局
- Plasma Metabolite Concentrations (µmol/L)(End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.)
- Fecal Metabolite Concentrations (nmol/mg dry weight)(End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.)
- Serum Cholesterol metabolism markers(End of the 10-day palmitic acid run-in period and end of the 28-day stearic acid intervention period.)
研究者
Nirupa Matthan
Scientist 1/Associate Professor
Tufts University