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

NCT05646901 | Recruiting

• 1 other identifier: GMBCrossTalk-Food-2022.166
• Study Type: observational
• Target: 116
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity

Keywords

Continous Glucose Monitoring; Cognition; Brain Iron content; microRNA

Outcome Measures

Primary Outcomes (27)

• Concentration of advanced glycation end products (AGE) receptor agonists.

  Enzyme-linked immunosorbent assay (ELISA).

  10 days

• Glycemic variability.

  Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.

  10 days

• The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)

  10 days

• The glycaemic risk measured with low blood glucose index (LBGI)

  Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic

  10 days

• The glycaemic risk measured with high blood glucose index (HBGI).

  High blood glucose index (HBGI) is a parameter that quantifies the risk of glycaemic.

  10 days

• The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE).

  measured in mg/dl

  10 days

• Minutes light sleep

  Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.

  10 days

• Minutes deep sleep

  Mean and standard deviation of minutes deep sleep measures by activity and sleep

  10 days

• Minutes rapid eye movement (REM)

  Mean and standard deviation of minutes REM measures by activity and sleep tracker device.

  10 days

• Effect on gut microbiota.

  Gut microbiota will be analysed by metagenomics and metabolomics.

  2 months

• Visual memory

  It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visual memory.

  10 days

• Audioverbal memory

  It will be measured by California Verbal Learning Test (CVLT). Minimum/maximum scale values (0-16), where 16 is a better audioverbal memory.

  10 days

• Depressive symptomatology

  It will be measured by Patient Health Questionnaire-9 (PHQ-9). Minimum/maximum scale values (0-27), where ≥ 20 is severe depression.

  10 days

• Impulsivity

  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).

  10 days

• Food Addiction

  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.

  10 days

• Behavioral inhibition

  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.

  10 days

• Behavioral activation

  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.

  10 days

• Visoconstructive function

  It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visoconstructive function.

  10 days

• Selective and alternating attention

  It will be measured by Trail making test (Part A y B).

  10 days

• Attention and working memory

  It will be measured by the Digits subtest of Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV).

  10 days

• Inhibition

  It will be measured by Stroop Color-Word Test.

  10 days

• Phonemic verbal fluency

  It will be measured by PMR

  10 days

• Semantic verbal fluency

  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.

  10 days

• Binge eating disorder

  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.

  10 days

• Anxiety

  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.

  10 days

• Facial recognition

  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.

  10 days

• Emotion recognition

  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.).

  10 days

Secondary Outcomes (25)

• Effect on brain structure.

  10 days

• Diffusion Tensor Imaging brain sequences

  24 hours

• Brain iron accumulation

  24 hours

• Resting-state functional brain sequences

  24 hours

• Insulin resistance

  10 days

Study Arms (6)

Premenopausal women with obesity

Postmenopausal women with obesity

Men with obesity

Premenopausal women without obesity

Postmenopausal women without obesity

Men without obesity

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

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

You may not qualify if:

• 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 40.
• Immunosuppressants treatment.
• Chronic constipation (depositional habit ≥ 7 days)

Sponsors & Collaborators

• Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta: lead

Study Sites (1)

Institut d'Investigació Biomèdica de Girona (IDIBGI)

Girona, Girona, 17007, Spain

RECRUITING

Related Publications (13)

• Ramirez V, Wiers CE, Wang GJ, Volkow ND. Personality traits in substance use disorders and obesity when compared to healthy controls. Addiction. 2020 Nov;115(11):2130-2139. doi: 10.1111/add.15062. Epub 2020 Apr 29.

  PMID: 32350970 BACKGROUND

• Volkow ND, Wang GJ, Tomasi D, Baler RD. The addictive dimensionality of obesity. Biol Psychiatry. 2013 May 1;73(9):811-8. doi: 10.1016/j.biopsych.2012.12.020. Epub 2013 Jan 29.

  PMID: 23374642 BACKGROUND

• Volkow ND, Wise RA. How can drug addiction help us understand obesity? Nat Neurosci. 2005 May;8(5):555-60. doi: 10.1038/nn1452. No abstract available.

  PMID: 15856062 BACKGROUND

• Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016 Aug;3(8):760-773. doi: 10.1016/S2215-0366(16)00104-8.

  PMID: 27475769 BACKGROUND

• Gearhardt AN, Corbin WR, Brownell KD. Development of the Yale Food Addiction Scale Version 2.0. Psychol Addict Behav. 2016 Feb;30(1):113-21. doi: 10.1037/adb0000136.

  PMID: 26866783 BACKGROUND

• Kalon E, Hong JY, Tobin C, Schulte T. Psychological and Neurobiological Correlates of Food Addiction. Int Rev Neurobiol. 2016;129:85-110. doi: 10.1016/bs.irn.2016.06.003. Epub 2016 Jul 22.

  PMID: 27503449 BACKGROUND

• Gupta A, Osadchiy V, Mayer EA. Brain-gut-microbiome interactions in obesity and food addiction. Nat Rev Gastroenterol Hepatol. 2020 Nov;17(11):655-672. doi: 10.1038/s41575-020-0341-5. Epub 2020 Aug 27.

  PMID: 32855515 BACKGROUND

• Gearhardt AN, Boswell RG, White MA. The association of "food addiction" with disordered eating and body mass index. Eat Behav. 2014 Aug;15(3):427-33. doi: 10.1016/j.eatbeh.2014.05.001. Epub 2014 May 27.

  PMID: 25064294 BACKGROUND

• Arnoriaga-Rodriguez M, Mayneris-Perxachs J, Burokas A, Contreras-Rodriguez O, Blasco G, Coll C, Biarnes C, Miranda-Olivos R, Latorre J, Moreno-Navarrete JM, Castells-Nobau A, Sabater M, Palomo-Buitrago ME, Puig J, Pedraza S, Gich J, Perez-Brocal V, Ricart W, Moya A, Fernandez-Real X, Ramio-Torrenta L, Pamplona R, Sol J, Jove M, Portero-Otin M, Maldonado R, Fernandez-Real JM. Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids. Cell Metab. 2020 Oct 6;32(4):548-560.e7. doi: 10.1016/j.cmet.2020.09.002.

  PMID: 33027674 BACKGROUND

• Arnoriaga-Rodriguez M, Mayneris-Perxachs J, Contreras-Rodriguez O, Burokas A, Ortega-Sanchez JA, Blasco G, Coll C, Biarnes C, Castells-Nobau A, Puig J, Garre-Olmo J, Ramos R, Pedraza S, Brugada R, Vilanova JC, Serena J, Barretina J, Gich J, Perez-Brocal V, Moya A, Fernandez-Real X, Ramio-Torrenta L, Pamplona R, Sol J, Jove M, Ricart W, Portero-Otin M, Maldonado R, Fernandez-Real JM. Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways. Gut. 2021 Dec;70(12):2283-2296. doi: 10.1136/gutjnl-2020-323371. Epub 2021 Jan 29.

  PMID: 33514598 BACKGROUND

• Williams MR, Stedtfeld RD, Tiedje JM, Hashsham SA. MicroRNAs-Based Inter-Domain Communication between the Host and Members of the Gut Microbiome. Front Microbiol. 2017 Sep 27;8:1896. doi: 10.3389/fmicb.2017.01896. eCollection 2017.

  PMID: 29021788 BACKGROUND

• Arnoriaga-Rodriguez M, Mayneris-Perxachs J, Burokas A, Perez-Brocal V, Moya A, Portero-Otin M, Ricart W, Maldonado R, Fernandez-Real JM. Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile. Microbiome. 2020 Apr 30;8(1):59. doi: 10.1186/s40168-020-00837-6.

  PMID: 32354351 BACKGROUND

• Mayneris-Perxachs J, Arnoriaga-Rodriguez M, Luque-Cordoba D, Priego-Capote F, Perez-Brocal V, Moya A, Burokas A, Maldonado R, Fernandez-Real JM. Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status. Microbiome. 2020 Sep 20;8(1):136. doi: 10.1186/s40168-020-00913-x.

  PMID: 32951609 BACKGROUND

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• José Manuel Fernández-Real, M.D., Ph.D.

  Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José Manuel Fernández-Real, M.D., Ph.D.

CONTACT

+34 972 94 02 00; jmfreal@idibgi.org

Marisel Rosell Díaz, M.D., MSc.

CONTACT

+34 972 94 02 00; mrosell@idibgi.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, clinical professor, section chief of Endocrinology and Nutrition Department of Josep Trueta University Hospital

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 12, 2022
• Study Start: December 12, 2022
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

ES (1)