Involvement of the Gut Microbiota-brain Cross-talk in the Loss of Eating Control (GMBCrossTalkFood)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Minutes deep sleep
研究概览
简要总结
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.
详细描述
The study includes a cross-sectional design (comparison of subjects with and without obesity) to assess parameters associated with food addiction through validated questionnaires. The metabolic and behavioral profile of the cohort and medial prefrontal cortex (mPFC) connectivity using fMRI will be characterized. The composition and functionality of the gut metagenome of these subjects will be analyzed in terms of its links to metabolic and behavioral parameters and imaging data. Since miRNAs may act as epigenomic mediators of metagenome effects impacting the brain, a broad profile of miRNAs circulating in plasma will also be analyzed.
Subjects and methods:
A cohort of subjects (n=100, 50% with obesity) will be recruited in whom parameters of food addiction (reward sensitivity, punishment sensitivity, and Yale Food Addiction Scale (YFAS 2.0 score) will be collected. The project will be carried out in subjects with obesity (25 men, 25 women, Body mass index (BMI) > = 30kg/m2) and subjects without obesity, similar in age and sex (25 men, 25 women, BMI <30kg/m2). A comprehensive metabolic profile (body weight, glucose and lipid profile, insulin resistance, blood pressure, and plasma and fecal metabolomics) will be analyzed.
A. Cross-sectional study:
Patients with obesity 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged 30-65 years.
- •Informed consent for participation in the study.
排除标准
- •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.
- •Persons whose liberty is under the legal or administrative requirement.
- •Clinical symptoms and signs of infection in the previous month.
- •Antibiotic, antifungal or antiviral treatment in the previous 3 months.
- •Anti-inflammatory chronic treatment with steroidal and/or non-steroidal anti-inflammatory drugs.
- •Major psychiatric antecedents.
- •Excessive alcohol intake, either acute or chronic (alcohol intake greater than 40 g a day (women) or 80 g/day (men)) or drug abuse.
- •Serum liver enzyme (AST, ALT) activity over twice the upper limit of normal.
- •History of disturbances in iron balance (e.g., genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
- •Creatinine greater than 1.2 and glomerular filtration rate less than
- •Immunosuppressants treatment.
- •Chronic constipation (depositional habit ≥ 7 days)
- •Kidney failure, history of a kidney transplant, or current treatment with dialysis.
- •Treatment with a slimming product during the previous two months.
- •Class III or IV heart failure (according to the New York Heart Association), medical records of ischemic cardiovascular disease.
- •Current treatment for malignant neoplasm.
结局指标
主要结局
Minutes deep sleep
时间窗: 10 days
Mean and standard deviation of minutes deep sleep measures by activity and sleep
The glycaemic risk measured with high blood glucose index (HBGI).
时间窗: 10 days
High blood glucose index (HBGI) is a parameter that quantifies the risk of glycaemic.
The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE).
时间窗: 10 days
measured in mg/dl
Minutes light sleep
时间窗: 10 days
Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.
Visual memory
时间窗: 10 days
It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visual memory.
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
时间窗: 10 days
Impulsivity
时间窗: 10 days
It will be measured by Impulsive Behavior Scale (UPPS-P). The test evaluates: Negative urgency (tendency to act rashly under extreme negative emotions), Lack of Premeditation (tendency to act without thinking), Lack of Perseverance (inability to remain focused on a task) and Sensation Seeking (tendency to seek out novel and thrilling experiences). All items are rated on a four point scale from 1 (strongly agree) to 4 (strongly disagree).
Behavioral inhibition
时间窗: 10 days
It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The scale of sensitivity to punishment is related to the behavioral inhibition system. It is made up of two subscales of 24 items each, where the higher the score, the greater the sensitivity to punishment.
Minutes rapid eye movement (REM)
时间窗: 10 days
Mean and standard deviation of minutes REM measures by activity and sleep tracker device.
Concentration of advanced glycation end products (AGE) receptor agonists.
时间窗: 10 days
Enzyme-linked immunosorbent assay (ELISA).
Glycemic variability.
时间窗: 10 days
Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.
Effect on gut microbiota.
时间窗: 2 months
Gut microbiota will be analysed by metagenomics and metabolomics.
Audioverbal memory
时间窗: 10 days
It will be measured by California Verbal Learning Test (CVLT). Minimum/maximum scale values (0-16), where 16 is a better audioverbal memory.
Attention and working memory
时间窗: 10 days
It will be measured by the Digits subtest of Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV).
Inhibition
时间窗: 10 days
It will be measured by Stroop Color-Word Test.
Food Addiction
时间窗: 10 days
It will be measured by Yale Food Addiction Scale.It is a symptom score from 0-11, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, for substance dependence. Food addiction is diagnosed if ≥3 symptoms are reported.
Visoconstructive function
时间窗: 10 days
It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visoconstructive function.
Facial recognition
时间窗: 10 days
It will be measured by Benton Facial Recognition Test. The participant is shown a face and then must recognize it among six faces placed together.
The glycaemic risk measured with low blood glucose index (LBGI)
时间窗: 10 days
Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic
Behavioral activation
时间窗: 10 days
It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The reward sensitivity scale is related to the behavioral activation system. It is made up of two subscales of 24 items each, where the higher the score, the greater the sensitivity to reward.
Semantic verbal fluency
时间窗: 10 days
It will be measured by Animals test. The person must name as many animals as possible in 1 minute. The result is corrected by standard scores, according to age and level of education.
Binge eating disorder
时间窗: 10 days
It will be measured by Binge Eating Scale (BES). The BES is one of the most widely used measures to assess binge eating disorder symptomatology. The BES score ranges from 0 to 46 and its cut-off point is greater than or equal to 27. Subjects with scores higher than 27 are more likely to suffer from binge eating disorder.
Anxiety
时间窗: 10 days
It will be measured by State-Trait Anxiety Inventory (STAI). This questionnaire evaluates state anxiety (S) and trait anxiety (R) through 20 items each, with a likert-type response scale of four alternatives. In the case of state anxiety, the scale goes from 0 (not at all) to 3 (a lot), while for trait anxiety it goes from 0 (almost never) to 3 (almost always). The higher the score, the greater the anxiety in both concepts.
Depressive symptomatology
时间窗: 10 days
It will be measured by Patient Health Questionnaire-9 (PHQ-9). Minimum/maximum scale values (0-27), where ≥ 20 is severe depression.
Selective and alternating attention
时间窗: 10 days
It will be measured by Trail making test (Part A y B).
Phonemic verbal fluency
时间窗: 10 days
It will be measured by PMR
Emotion recognition
时间窗: 10 days
It will be measured by Pictures of Facial Affect. The participant will be shown pictures of people and has to recognize what emotion the subjects of the pictures are expressing ( happiness, sadness, etc.).
次要结局
- Diffusion Tensor Imaging brain sequences(24 hours)
- Brain iron accumulation(24 hours)
- The percentage of time in hypoglycaemia (glucose level below 70mg/dl)(10 days)
- The percentage of time in glucose range (glucose level above 200 mg/dl)(10 days)
- Effect on brain structure.(10 days)
- Minutes slight activity(10 days)
- Calories(10 days)
- Glycosylated hemoglobin (HbA1c) value(10 days)
- The percentage of time in hyperglycaemia (glucose level above 250 mg/dl)(10 days)
- The percentage of time in glucose range (glucose level below 100 mg/dl)(10 days)
- The percentage of time in glucose range (glucose level between 126-139 mg/dl)(10 days)
- Steps(10 days)
- Minutes null activity(10 days)
- Minutes awake(10 days)
- Number time awake(10 days)
- Resting-state functional brain sequences(24 hours)
- Insulin resistance(10 days)
- Markers of chronic inflammation: C-reactive protein, IL-6, adiponectin and soluble, tumor necrosis factor-α receptor fractions.(2 months)
- Burned calories(10 days)
- Distance(10 days)
- Minutes asleep(10 days)
- Bed time(10 days)
- The percentage of time in glucose range (glucose level between 140-199 mg/dl)(10 days)
- Minutes mean activity(10 days)
- Minutes high activity(10 days)
研究者
José Manuel Fernández-Real
Principal investigator, clinical professor, section chief of Endocrinology and Nutrition Department of Josep Trueta University Hospital
Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta