Involvement of the Gut Microbiota-brain Cross-talk in the Loss of Eating Control

Summary

Overweight and obesity are increasingly prevalent worldwide. These bodyweight disorders are closely related to deficiencies in the control of food intake. A potential yet unexplored mechanism to explain the loss of eating control is the interaction between the gut microbiota and the brain. The mechanisms underlying the communication between the gut microbiome and the host remain largely unexplored. These mechanisms could occur in part through small non-coding RNAs, called microRNAs (miRNAs). miRNAs regulate epigenetic mechanisms to control gene expression. Two hypotheses have been proposed: I. The interaction between the gut microbiota and the brain and its associated epigenetic changes play an important role in the overweight-related loss of eating control and metabolic imbalance. II.The composition and functionality of the gut microbiota are associated with circulating microRNAs and glycemic variability and modify the effect of physical activity on cognitive parameters and brain microstructure (R2\*). The study includes a cross-sectional design (comparison of subjects with and without obesity) to evaluate parameters associated with food addiction through validated questionnaires. The metabolic and behavioral profiles of the cohort will be characterized. The medial prefrontal cortex connectivity will be studied using functional magnetic resonance imaging (fMRI). The composition and functionality of the gut metagenome of the subjects will be analyzed in association with metabolic and behavioral parameters and imaging data. miRNAs can act as mediators of epigenomics of the effects of the metagenome that impact the brain, therefore it will be analyzed a broad profile of miRNAs circulating in plasma.

Eligibility

Inclusion Criteria:

1. Men and women aged 30-65 years.
2. Informed consent for participation in the study.

Exclusion Criteria:

1. Serious systemic disease unrelated to obesity such as cancer, severe kidney, or liver disease, known as type 1 or type 2 diabetes.
2. Systemic diseases with intrinsic inflammatory activity such as rheumatoid arthritis, Crohn's disease, asthma, chronic infection (e.g., HIV, active tuberculosis), or any type of infectious disease.
3. Pregnancy and lactation.
4. Patients with severe disorders of eating behavior.
5. Persons whose liberty is under the legal or administrative requirement.
6. Clinical symptoms and signs of infection in the previous month.
7. Antibiotic, antifungal or antiviral treatment in the previous 3 months.
8. Anti-inflammatory chronic treatment with steroidal and/or non-steroidal anti-inflammatory drugs.
9. Major psychiatric antecedents.
10. Excessive alcohol intake, either acute or chronic (alcohol intake greater than 40 g a day (women) or 80 g/day (men)) or drug abuse.
11. Serum liver enzyme (AST, ALT) activity over twice the upper limit of normal.
12. History of disturbances in iron balance (e.g., genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
13. Creatinine greater than 1.2 and glomerular filtration rate less than 40.
14. Immunosuppressants treatment.
15. Chronic constipation (depositional habit ≥ 7 days)
16. Kidney failure, history of a kidney transplant, or current treatment with dialysis.
17. Treatment with a slimming product during the previous two months.
18. Class III or IV heart failure (according to the New York Heart Association), medical records of ischemic cardiovascular disease.
19. Current treatment for malignant neoplasm.

Conditions2

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