Clinical trial NCT04823533: Improving Wellbeing Through the Brain-Gut-Microbiota Axis
Official title: A Psychophysiological Study of the Bidirectional Communication Mechanisms Between the Brain and the Gastrointestinal System and Its Effects on Well-being
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Lifestyle
Keywords: Microbiota
Brain-gut
Wellbeing
Interoception
Probiotic
Electrophysiology
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
Collaborators: name: University of Chile
name: Instituto de Nutrición y Tecnología de los Alimentos
name: University Diego Portales
name: Lallemand SAS
First posted: 2021-03-30
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: BASIC_SCIENCE

Brief summary: Well-being is a state defined as the optimal psychological functioning and the experience associated with it, integrating physical and subjective factors. It has been suggested that the bidirectional interaction between the brain and the rest of the body is fundamental in the regulation of wellbeing levels. In particular, the gastrointestinal system (modulated by the microbiota) sends information that is integrated by the brain, affecting its functioning and mental processes. However, the mechanism of such communication is still unknown. The aim of this proposal is to study the different ways in which psychological processes can influence gut signals and vice versa, and how this relationship might be trained or modified in order to improve wellbeing.

Detailed description: Within the field of Psychology and Contemplative Sciences, the relationship and interdependence between the brain and body have been one of the most prevalent questions when it comes to understanding the psychobiological mechanisms underlying human behavior. It is proposed that the brain should be seen as a dynamic, complex, and self-organized system, which is closely coupled and integrated with whole-body signals, establishing a two-way communication axis. This has been evidenced through an increase in scientific research adopting an embodied perspective that considers both diverse brain measurements as well as signals from other parts of the body, such as the heart and the gastrointestinal system. Recent pieces of evidence have furthermore begun to reveal the different ways in which psychological processes can influence the body, and how this could be trained in order to improve wellness.

Interoception is a cognitive process developed to monitor the internal state of the body and it involves the continuous and dynamic integration of information from different (internal) origins, including respiratory, cardiac, and gastrointestinal systems. New research agendas have started to link interoception to wellbeing, and with the psychopathology of psychiatric conditions, from depression and autism to eating disorders. Interestingly, it has been shown that this ability can be trained through contemplative practices designed to improve body awareness, socio-affective and socio-cognitive capacity. Moreover, some interoceptive dimensions like thirst interoception might be affected by lifestyle and habits such as diet. Altogether, this evidence suggests that understanding the mechanism of brain-body integration represents a promising alternative to improve wellbeing and mental health.

One example of psychophysical integration that has taken much importance in recent years, due to its implications on wellbeing and mental health, is the one established between the brain and the gastrointestinal system. In particular, gut-microbiota research is acquiring special importance because of its implications in psychological states such as stress and anxiety, and psychiatric conditions like depression and autism. It has been shown that microbiota affects brain functioning through different pathways including neural, humoral, and endocrine. However, the mechanism of brain-gut-microbiota integration and its relationship to wellbeing is still unknown. The integration of information through large-scale oscillation coupling has been one of the most validated proposals regarding signal processing and communication. An oscillatory coupling between the brain and the gastrointestinal system was recently described, shedding light on a possible mechanism via which the gastrointestinal system constantly and instantaneously sends information to the brain, which in turn integrates this information either consciously or unconsciously, thus affecting mental processes.

This research proposal aims to study how the brain integrates information from the gut (regulated by the microbiota) and the relevance of this coupling on wellbeing. To do this, the oscillatory coupling between the electroencephalogram (EEG) and electrogastrogram (EGG) signals will be recorded and evaluated. EEGs and EGGs will be recorded under different interventions including training designed to increase interoceptive gastric awareness and treatment with probiotics to modify some microorganisms that have already been associated with mental health. The oscillatory coupling will be compared to the well-being observed after each of the interventions. In this investigation, wellbeing will be defined as optimal psychological functioning, integrating physical and subjective factors, and will be evaluated through different self-reported questionnaires.

Interventions related to improving body awareness and contemplative practices, in general, are helping to improve the levels of wellness around the world and in Chile, representing an accessible and cheap way to manage psychological conditions regardless of socioeconomic and demographic aspects, contributing to the development of new therapeutic strategies. Additionally, a strong relationship between diet, microbiota, and health has now been demonstrated. Thus, understanding the mechanism via which the microbiota communicates with the brain, the susceptibility of this communication to microbiota changes, and the relationship of this process with participants' diet could provide relevant information when making decisions related to eating habits and lifestyles.

Eligibility criteria: Inclusion Criteria:

1. Healthy adults of ≥ 18 to \& 65 years old of age.
2. Able to provide written consent.
3. Willing to provide stool samples and complete questionnaires, records, and diaries associated with the study
4. Willingness to discontinue consumption of probiotic supplements for the duration of the study.

Exclusion Criteria:

1. Concurrent consumption of probiotics. Subjects will be eligible for participation, however, after a four (4) week wash-out period.
2. Known to be pregnant or breastfeeding or planning on becoming pregnant in the next two (2) months.

   Positive pregnancy test in women of childbearing potential.
3. Use of antibiotic drugs (e.g., neomycin, rifaximin) within 1 month of the screening visit. The screened participant would be eligible to participate four (4) weeks after completing their course of antibiotics (wash-out period).
4. Subject with diabetes or metabolic diseases.
5. Subject with depression or psychiatric and neurological diseases.
6. Subject with IBS or gastrointestinal diseases.
7. Subject with immune disorders or with possible immune-deficient status (e.g. due to surgery).
8. Milk or soy allergy.

Primary outcomes:
measure: Difficulties in Emotion Regulation Scale (DERS) at baseline
timeFrame: Week 0
measure: Difficulties in Emotion Regulation Scale (DERS) after intervention
timeFrame: Week 4
measure: Difficulties in Emotion Regulation Scale (DERS) - follow up
timeFrame: Week 12
measure: Ryff Scales of Psychological Well-Being (PWB) at baseline
timeFrame: Week 0
measure: Ryff Scales of Psychological Well-Being (PWB) post intervention
timeFrame: Week 4
measure: Ryff Scales of Psychological Well-Being (PWB) - follow-up
timeFrame: Week 12
measure: Satisfaction With Life Scale (SWLS) at baseline
timeFrame: Week 0
measure: Satisfaction With Life Scale (SWLS) post intervention
timeFrame: Week 4
measure: Satisfaction With Life Scale (SWLS) - follow-up
timeFrame: Week 12
measure: The State-Trait Anxiety Inventory (STAI) - State at baseline
timeFrame: Week 0
measure: The State-Trait Anxiety Inventory (STAI) - State post intervention
timeFrame: Week 4
measure: The State-Trait Anxiety Inventory (STAI) - State - follow-up
timeFrame: Week 12
measure: Positive and Negative Affect Schedule (PANAS) at baseline
timeFrame: Week 0
measure: Positive and Negative Affect Schedule (PANAS) post intervention
timeFrame: Week 4
measure: Positive and Negative Affect Schedule (PANAS) - follow-up
timeFrame: Week 12
measure: The Five Facet Mindfulness Questionnaire (FFMQ) at baseline
timeFrame: Week 0
measure: The Five Facet Mindfulness Questionnaire (FFMQ) post intervention
timeFrame: Week 4
measure: The Five Facet Mindfulness Questionnaire (FFMQ) - follow-up
timeFrame: Week 12
measure: Gut microbiota
timeFrame: Week 0
measure: Water load test (Gastric Interoception) at baseline
timeFrame: Week 0
measure: Water load test (Gastric Interoception) post intervention
timeFrame: Week 4
measure: Water load test (Gastric Interoception) - follow-up
timeFrame: Week 12
measure: Multidimensional questionnaire of interoceptive awareness (MAIA) at baseline
timeFrame: Week 0
measure: Multidimensional questionnaire of interoceptive awareness (MAIA) post intervention
timeFrame: Week 4
measure: Multidimensional questionnaire of interoceptive awareness (MAIA) follow-up
timeFrame: Week 12
measure: Brain-gut coupling using the modulation index
timeFrame: Week 0
Secondary outcomes:
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Pontificia Universidad Católica de Chile
state: Region Metropolitana
Study officials:
References: