Investigation of the Mechanisms of the Gut-brain Axis in Binge Eating and Obesity.

Condition(s) studied

Investigational drug(s) / intervention(s)

Psychobiotic treatment: The dietary supplementation will follow established guidelines, recommending an intake of 16 g of prebiotic per day, distributed across three meals, for a duration of 12 weeks.

Placebo treatment: The control group will receive identical packaging that matches the experimental treatment in taste and appearance and will follow the same guidelines for consuming the placebo. For ethical reasons, after the end of the RCT, the control group will be given the option to receive the same prebiotic supplement.

Study summary

Binge Eating Disorder (BED) is a recently recognized eating disorder, characterized by recurrent episodes of overeating with a loss of control. Highly comorbid with obesity, BED is associated with poor outcomes in weight loss treatments and presents unique challenges due to its distinct neuro-psycho-biological mechanisms, which remain poorly understood. The Microbiota-Gut-Brain Axis (MGBA) is a bidirectional communication system linking the gut microbiota with the central nervous system, that plays a critical role in regulating appetite, mood, and eating behavior. Dysregulations in MGBA may contribute to the development and maintenance of BED, offering a novel framework for understanding its complex mechanisms and identifying new therapeutic targets. Psychobiotics -pre-, pro-, or symbiotics that modulate the microbiota- emerge as a promising treatment strategy to address BED symptoms by influencing MGBA activity.

The goal of this randomized clinical trial (RCT) is to investigate the role of psychobiotics in modulating the gut-brain axis and improving binge eating in adults, with a particular focus on evaluating these effects independently of obesity status. This project stands out for its comprehensive approach to understanding BED, integrating psychological, neurofunctional, hormonal, and microbiota factors that contribute to this complex disorder.

The main questions it aims to answer are:

* What specific alterations in the MGBA pathways are associated with BED?
* Can psychobiotic supplementation effectively reverse microbiota alterations and modulate MGBA activity, ultimately improving BED symptoms? Researchers will compare participants receiving psychobiotics to those receiving a look-alike substance that contains no drug (a placebo) to evaluate whether psychobiotics impact endocrine hormones, neurofunction, psychological and behavioral factors related to eating regulation, and BED symptoms.

Participants will:

* Undergo an assessment protocol that includes microbiota sampling, blood tests for hormone analysis, neurofunctional evaluations, and psychological/behavioral assessments before and after the psychobiotics/ placebo intervention.
* Take psychobiotics or a placebo daily for 12 weeks and receive well-being monitoring
* Participate in follow-up visits three months after the intervention to monitor changes in BED symptoms and related parameters.

Eligibility

Primary outcome measure(s)

• Gut Microbiota outcomes - Gut-Bacteria Composition — Change measures: baseline and end of treatment at 12 weeks
  Stool samples from each participant will be fermented by the prebiotic to allow direct comparison of individual alterations in vitro and in vivo of the microbiome. Changes in gut-bacteria composition and its adhesion into the mucus layer will be analyzed.
• Gut Microbiota outcomes - Molecules released by the gut-bacteria — Change measures: baseline and end of treatment at 12 weeks
  Stool samples from each participant will be fermented by the prebiotic to allow direct comparison of individual alterations in vitro and in vivo of the microbiome. Molecules released by the bacteria, including short-chain fatty acids (SCFA), lipopolysaccharides (LPS), gamma-aminobutyric acid (GABA), dopamine, and serotonin, which modify host metabolism and central regulation of appetite directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, will be traced during fermentations.
• Psycho-behavioral outcomes - Three Factor Eating Questionnaire-21 — Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
  Three Factor Eating Questionnaire-21 (TFEQ-21): assesses psychopathology and behaviors related to eating disorders, generating 3 subscales: emotional eating; compulsive eating; restraint eating.
• Psycho-behavioral outcomes - Eating Expectancy Inventory — Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
  \- The Eating Expectancy Inventory (EEI): evaluates cognitive expectations regarding eating
• Psycho-behavioral outcomes - Negative urgency subscale — Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
  Negative urgency subscale from the Urgency, Premeditation, Perseverance, and Sensation Seeking scales (UPPS): assesses the tendency to act rashly/impulsively when experiencing negative emotions.
• Psycho-behavioral outcomes - Difficulties in Emotion Regulation Scale — Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
  Difficulties in Emotion Regulation Scale (DERS): self-report measure developed to assess difficulties in emotional dysregulation.
• Psycho-behavioral outcomes - Distress Tolerance Scale — Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
  The Distress Tolerance Scale (DTS): scale that assesses ability to experience, tolerate, and function in a context of emotional distress
• Neurofunctioning outcomes - Default mode network — Change measures: baseline and end of treatment at 12 weeks
  Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The DMN is involved in self-referential processing, which includes monitoring the external environment as well as physical and emotional states.
• Neurofunctioning outcomes - Salience network — Change measures: baseline and end of treatment at 12 weeks
  Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The DMN is involved in self-referential processing, which includes monitoring the external environment as well as physical and emotional states. The SN is involved in detecting the salience of stimuli, integrating emotional arousal, food, and reward processing.
• Neurofunctioning outcomes - Meso/Paralimbic network — Change measures: baseline and end of treatment at 12 weeks
  Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The MPN is involved in processing emotional information and interoceptive awareness.
• Neurofunctioning outcomes - Executive network — Change measures: baseline and end of treatment at 12 weeks
  Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The EN is involved in cognitive control and inhibitory processes, such as the termination of food consumption
• Appetitive hormones outcomes - Ghrelin — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: * Ghrelin is an orexigenic hormone with stimulatory effects on appetite and food intake.
• Appetitive hormones outcomes - Glucagon-Like Peptide 1 — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: * Glucagon-Like Peptide 1 (GLP-1) have an anorexigenic effect and are thought to contribute to impaired satiation and binge eating tendencies. GLP-1 has been the target of novel therapeutics for weight loss, but few studies have examined its impact on BED.
• Appetitive hormones outcomes - Peptide YY — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: \- Peptide YY (PYY) have an anorexigenic effect and are thought to contribute to impaired satiation and binge eating tendencies.
• Appetitive hormones outcomes - Leptin — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: * Leptin acts as a regulatory signal reflecting the adipose tissue stores. Both insufficiency and resistance to its actions promote hunger and increased food intake. Leptin can decrease food reward and act in the central nervous system as regulators of energy homeostasis.
• Appetitive hormones outcomes - Insulin — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: Insulin can decrease food reward and act in the central nervous system as regulators of energy homeostasis.
• Appetitive hormones outcomes - Cortisol — Change measures: baseline and end of treatment at 12 weeks
  Assessment of appetitive hormones that modulate eating behavior: \- Cortisol is responsible for the stress response, acting on the hypothalamic-pituitary axis, and it is associated with increased eating

Trial sites (1)

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