Obesity
Conditions
Keywords
Obesity, Butyrate, Gut microbiota, mitochondria, monocyte, short chain fatty acid
Brief summary
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.
Detailed description
The study will consist of a screening phase (pre-admission) and two visits, followed by asynchronous follow-up. Pre-admission visit Participants meeting inclusion criteria (presence of obesity) will be recruited through advertisements published on official institutional platforms. Informed consent will be explained and signed prior to any study-related procedures. Participants will be informed about the study characteristics, procedures, risks, and expected benefits, including dietary intervention and biochemical assessments. A clinical history will be obtained, including identification data, contact information, medical history, and current or recent use of medications and supplements. Anthropometric measurements (weight and height) will be obtained for BMI calculation. Blood pressure will be measured after at least 5 minutes of rest, with two readings per arm separated by 3 minutes and averaged. A blood sample will be collected to determine glucose, creatinine, and liver function tests. Eligible participants will receive a stool collection kit with instructions for microbiota analysis and will be instructed to return the sample at the next visit. Visit 1: Baseline Anthropometric measurements will be recorded (weight, height, waist circumference). Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function. The stool sample collected will be received for microbiota and short-chain fatty acids analysis. Intervention Participants will be randomly assigned to either: Butyrate supplement group, or placebo group. An isocaloric maintenance diet will be prescribed (50% carbohydrates, 20% protein, 30% fat, 25 g/day fiber), including menus and food lists. Study capsules will be provided along with: Instructions for administration, adherence logbook, identification of adverse event monitoring (nausea, vomiting, abdominal discomfort, diarrhea, constipation, headache, dizziness, fatigue) Visit 2: Final (After 4 weeks of intervention) Nutritional and Clinical Assessment Anthropometric measurements will be recorded (weight, height, waist circumference). Body composition will be assessed using bioimpedance (fat mass, lean mass). Blood pressure will be measured following standardized procedures. A 24-hour dietary recall will be administered. The International Physical Activity Questionnaire will be applied. A blood sample will be collected to assess: Glucose, A blood sample will be collected to assess: Glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, liver enzymes, C-reactive protein, interleukin 6 and mitochondrial function and mitochondrial function. The stool sample collected will be received for microbiota and short-chain fatty acids analysis. Capsule count and adherence log review will be conducted. The adverse events questionnaire will be administered.
Interventions
DIETARY_SUPPLEMENTPlacebo
Oral 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.
DIETARY_SUPPLEMENTCalcium butyrate
Oral 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.
Sponsors
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signing of the informed consent form. * Adults aged ≥18 years of age. * Body mass index (BMI) \>30 kg/m². * Both sex
Exclusion criteria
* 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. * Secondary causes of obesity or diabetes, including Cushing syndrome, clinical or subclinical hypothyroidism, or pheochromocytoma. * Catabolic diseases such as cancer or acquired immunodeficiency syndrome. Drug treatment: * Antihypertensive drugs or treatment (thiacycline, loop or potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, alpha blockers, calcium antagonists, beta blockers). * Treatment with hypoglycemic agents (sulfonylureas, biguanides, incretins) or insulin and antidiabetic drugs. * Treatment with statins, fibrates or other drugs to control dyslipidemia. * Use of antibiotics in the three months prior to the study. * Use of steroid drugs, chemotherapy, immunosuppressants, or radiation therapy. * Anorexigenic or that accelerate weight loss such as sibutramine or orlistat. * Supplements with any of the functional foods used in the study. * Probiotic, prebiotic or symbiotic supplements. * Chronic proton pump inhibitor use or use within the last 2 weeks. * Chronic use of laxatives, antispasmodics, or medications affecting intestinal motility. * Current tobacco use. * Daily alcohol consumption \>1 drink/day during the last month. * Use of recreational psychoactive substances. * Pregnancy or lactation. * Bariatric surgery or participation in intensive weight loss programs. * Weight loss ≥3 kg in less than 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monocyte mitochondrial maximal respiration in pmol O₂/min/10⁶ | From baseline to week 4 of the intervention | 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 | From baseline to week 4 of the intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monocyte mitochondrial reserve respiratory capacity in pmol O₂/min/10⁶ cells | From baseline to week 4 of the intervention | 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 | From baseline to week 4 of the intervention | 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 | From baseline to 4 week of the intervention | Change in fecal butyrate concentration measured in stool samples by gas chromatography, and compared between the intervention and placebo groups. |
Countries
Mexico
Contacts
CONTACTMartha Guevara, MD, PhD
CONTACTLilia Noriega, PhD
STUDY_DIRECTORMartha Guevara, PhD
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Outcome results
None listed