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.
Men and women aged 30-65 years.
Informed consent for participation in the study.
Serious systemic disease unrelated to obesity such as cancer, severe kidney, or liver disease, known as type 1 or type 2 diabetes.
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.
Pregnancy and lactation.
Patients with severe disorders of eating behavior.
Patients with obesity, without known type 2 diabetes, previously scheduled at the Service of Endocrinology, Diabetes, and Nutrition (UDEN) of the Hospital "Dr. Josep Trueta" of Girona (Spain) will be recruited and studied. Subjects without obesity will also be recruited through a public announcement.
Case-control
Prospective
Not listed
6
Trial groupsSee each trial group below.
Concentration of advanced glycation end products (AGE) receptor agonists.
Enzyme-linked immunosorbent assay (ELISA).
Glycemic variability.
Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
The glycaemic risk measured with low blood glucose index (LBGI)
Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic
Effect on brain structure.
Brain structure will be assessed using magnetic resonance imaging.
Diffusion Tensor Imaging brain sequences
Diffusion Tensor Imaging was acquired at 1.5 T (Philips ingenia) using a single-shot spin echo sequence with echo-planar imaging (EPI), 50 contiguous slices, voxel size 2x2x2.5 mm3, TE/TR of 72/3581 ms/ms, a diffusion-weighting factor b = 800 s/mm2 and diffusion encoding along 32 directions.
Brain iron accumulation
It will be assessed using magnetic resonance imaging using (R2\*)
Resting-state functional brain sequences
It will be assessed using magnetic resonance imaging (T2\*-weighted echo-planar imaging). T2 \* relaxation data will be acquired with a multi-echo gradient sequence with 10 equidistant echoes (first echo = 4.6ms; echo spacing = 4.6ms; repetition time = 1300ms). The value value of T2 \* will be calculated by adjusting the simple exponential terms for the signal decay of the respective echo time values.
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