Obesity is characterized by gut microbiota dysbiosis, in which beneficial metabolites such as butyrate are reduced. Butyrate is a short-chain fatty acid produced by microbial fermentation that plays a key role in maintaining intestinal barrier integrity, regulating immune responses, and supporting mitochondrial function. Its depletion contributes to disruption of the intestinal barrier, facilitating the translocation of bacterial components and promoting systemic inflammation mediated by immune cell activation, like monocytes. This chronic inflammatory state is associated with mitochondrial dysfunction and impaired cellular bioenergetics. Butyrate has been investigated for its anti-inflammatory and metabolic effects, however, its direct impact on monocyte mitochondrial function and its relationship with gut microbiota composition in humans remains unclear.
This randomized, double-blind, placebo-controlled trial will evaluate the effect of oral calcium butyrate supplementation (1000 mg/day) compared with placebo for 4 weeks in adults with obesity. The primary objective is to determine the change in monocyte mitochondrial maximal respiration baseline to week 4.
Signing of the informed consent form.
Adults aged ≥18 years of age.
Body mass index (BMI) >30 kg/m².
Both sex
Diabetes mellitus, defined as fasting glucose >126 mg/dL during screening.
Hypertension, defined as blood pressure ≥130/80 mmHg during screening.
Chronic kidney disease or estimated glomerular filtration rate <60 mL/min/1.73 m².
Known liver disease.
Parallel
Placebo
Dietary supplementOral placebo capsules containing maltodextrin, 300 mg per capsule. Participants assigned to the placebo comparator arm will take two capsules once daily, for a total dose of 600 mg/day, for 4 weeks.
Calcium butyrate
Dietary supplementOral calcium butyrate capsules, 500 mg per capsule. Participants assigned to the experimental arm will take two capsules once daily, for a total dose of 1000 mg/day, for 4 weeks.
Monocyte mitochondrial maximal respiration in pmol O₂/min/10⁶
Change in maximal respiration measured in Cluster of differentiation 14 (CD14+) monocytes using extracellular flux mitochondrial stress testing. Maximal respiration will be calculated as peak oxygen consumption rate (OCR) after Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) stimulation minus non-mitochondrial respiration, and compared between the intervention and placebo groups.
Gut microbiota composition as relative abundance percentage
Changes in gut microbiota composition will be assessed by 16 svedberg unit (16S) ribonucleic acid ribosomal (rRNA) sequencing, including alpha diversity (Chao1, Shannon), beta diversity, and relative taxonomic. and compared between the intervention and placebo groups.
Monocyte mitochondrial reserve respiratory capacity in pmol O₂/min/10⁶ cells
Change in reserve respiratory capacity measured in CD14+ monocytes using extracellular flux mitochondrial stress testing, will be calculated as the difference between maximal oxygen consumption rate and basal oxygen consumption rate, and compared between the intervention and placebo groups.
Monocyte Bioenergetic Health Index (BHI) score
Change in Bioenergetic Health Index measured in CD14+ monocytes using extracellular flux mitochondrial stress test. BHI will be calculated as (ATP-linked respiration × spare respiratory capacity) / (proton leak × non-mitochondrial respiration), and compared between the intervention and placebo groups.
Fecal butyrate concentration in µmol/g
Change in fecal butyrate concentration measured in stool samples by gas chromatography, and compared between the intervention and placebo groups.
Body mass index in kg/m²
Change in body mass index calculated as weight in kilograms divided by height in meters squared, and compared between the intervention and placebo groups.
Skeletal muscle mass percentage
Change in skeletal muscle mass measured by bioimpedance, and compared between the intervention and placebo groups.
Waist circumference in centimeter
Change in waist circumference measured at the midpoint between the lower costal margin and the iliac crest at the end of a normal expiration, and compared between the intervention and placebo groups.
Lean body mass percentage
Change in lean body mass measured by bioimpedance, and compared between the intervention and placebo groups.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
