Clinical trial NCT04315714: Impact of a Yoga Intervention on Pain and Multiomics in Participants With IBS
Official title: Impact of a Yoga Intervention on Chronic Abdominal Pain, and Associations With the Metagenome and Metabolome in Participants With IBS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Abdominal Pain
Keywords: Irritable bowel syndrome
IBS
Yoga
Microbiome
Abdominal pain
Metagenome
Metabolome
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute of Nursing Research (NINR)
First posted: 2020-03-19
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This will be a randomized, controlled trial crossover design, evaluating a yoga intervention, delivered online/virtually via Zoom, with a wait-list control condition for 6 weeks. Study participants will be crossed over to the alternative intervention for an additional 6 weeks, with total intervention time of 12 weeks. Twenty participants with irritable bowel syndrome (IBS) and 20 healthy controls (HC) will be recruited; 10 participants with IBS will be randomized to the yoga intervention at the beginning of the trial, and 10 participants with IBS randomized to the waitlist control condition. Likewise, 10 HC participants will be randomized to the yoga intervention at the beginning of the trial, and 10 HC will be randomized to the waitlist control condition.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research study is to see if a six-week yoga program delivered online/virtually via Zoom, reduces abdominal pain in people with irritable bowel syndrome (IBS). This study also looks at whether the yoga program changes the composition of microorganisms in the gut and their metabolites, and compares the program in people with IBS versus healthy people (also known as "healthy controls" or "HC"). People in this study are randomized (like flipping a coin) to one of two conditions: half of the people attend the online/virtual private yoga program delivered via Zoom for the first six-weeks, and half of the people wait for six-weeks and then attend the online/virtual private yoga program for six-weeks. The hypothesis of this study is that the practice of yoga induces shifts in the gut microbiota and microbial-derived metabolites, which will correlate with diminished abdominal pain.

Detailed description: Chronic abdominal pain is a hallmark feature of irritable bowel syndrome (IBS)1; a prevalent2, costly disorder3 that disproportionately affects the female sex4. IBS is often comorbid with psychiatric disorders and other pain-related conditions, and although pathophysiology is not yet fully understood, alterations in the gut microbiota, epithelial barrier and immune response are among factors noted to play a role5. Bidirectional signaling between the brain, the gut, and its microbiome is relevant to the disorder of IBS, with top-down signaling including through the autonomic nervous system, and bottom-up signaling through microbial-derived intermediates including secondary bile acids, short-chain fatty acids (SCFA), and tryptophan metabolites6. Diet and lifestyle are critical determinants of the microbiota composition7, thus interventions which modulate the microbiota and affect microbial-derived intermediates, have the potential to improve patient symptomatology. A recent meta-analysis of common dietary interventions for IBS, however, demonstrates insufficient evidence to recommend a gluten-free diet, and very low quality evidence supporting the efficacy a low fermentable oligo-di-and monosaccharides and polyols (FODMAP) diet to reduce symptoms of IBS8. Therefore, a need exists to identify alternative lifestyle interventions for patients with IBS, and given the acknowledged role of the microbiota in pathophysiology, enhance our understanding of how such interventions modulate the microbiota, affect microbial-derived intermediates, and influence patient symptoms of chronic abdominal pain.

A lifestyle intervention of increasing interest in IBS research is physical activity; a recent systematic review suggests exercise to improve gastrointestinal (GI) symptoms, anxiety, depression, stress, and quality of life9. The practice of yoga, in particular, benefits anxiety, quality of life and GI symptoms in patients with IBS10, although physiological underpinnings of this effect remain understudied in IBS. A recent meta-analysis of randomized controlled trials comparing the practice of yoga asanas (body postures) with active controls across patient populations, reports yoga to improve cortisol, cytokines, autonomic measures, fasting blood glucose and lipids11. An additional pathway by which yoga may affect symptomatology in IBS is along the gut microbiota-skeletal muscle axis. Preclinical findings report the gut microbiota to influence skeletal muscle mass and function in mice, with germ free mice displaying altered amino acid metabolism12. Importantly, this gut-muscle axis appears bi-directional, in that microbiota may modulate muscle function through nutrient synthesis and biotransformation, whereas regular exercise can modulate the composition of the microbiota, and enhance gut microbiota diversity13. Exercise training has been found to increase concentrations of SCFA including butyrate14, a microbial end product with beneficial effects upon intestinal inflammation, immunity and gut barrier function15, and levels of which have been noted as altered in patients with IBS in comparison with healthy controls (HC)16. The gut microbiota of patients with IBS compared with HC, consistently includes lower microbial α-diversity, decreased levels of Bacteroidetes, increased levels of Firmicutes, and increased F/B ratio17. Metagenomics and metabolomics used in combination, can provide a comprehensive overview of microbiome-host interactions18. This was demonstrated by a recent investigation of children with IBS and HC, in which IBS children were found to be enriched in bacterial taxa (e.g. Flavonifractor plautii), metagenomics functional profile (e.g. amino acid metabolism), higher-order metabolites (e.g. secondary bile acids), and associations were noted with abdominal pain19.

The investigators of this study hypothesize that participants with IBS differ from HC in lower microbial α-diversity and reduced SCFA (specifically butyrate), which will be associated with abdominal pain. Furthermore, the investigators of this study hypothesize that the practice of yoga induces shifts in the gut microbiota and microbial-derived metabolites, specifically butyrate, which will correlate with diminished abdominal pain. To test these hypotheses, the investigators of this study propose the following two aims:

Specific Aim 1: Identify differences in microbial features and metabolites among participants with IBS and HC at baseline, and evaluate associations with participant characteristics

Specific Aim 2: Determine if a 6-week yoga intervention delivered online/virtually via Zoom, reduces abdominal pain among participants with IBS, and evaluate associations with microbial features and metabolites.

Findings from this study will enhance our understanding of the interplay between the microbiota, microbial-derived intermediates and pain in patients with IBS. Furthermore, this research will facilitate the identification of relevant microbial features and metabolites that may prove modifiable, and work towards diminishing the public health burden surrounding chronic pain.

Eligibility criteria: Inclusion Criteria:

* Ability to read/write in English
* Access to smartphone/computer/email; Internet and camera access for online/virtual yoga sessions via Zoom
* Physical ability to engage in twice weekly yoga for 6 weeks (60 minutes each session), with physical clearance provided by current healthcare provider
* Diagnosis of IBS and IBS subtype (for cases), with documentation provided by current healthcare provider
* Self-report average, abdominal pain over past 7 days ≥ 3 (for cases: on 0-10 scale)
* Willingness to participate in all study procedures

Exclusion Criteria:

* Regular yoga practice (past 3 months)
* Recent antibiotic use (past 3 months)
* Consumption of a strict vegan/vegetarian diet
* Plan to initiate prebiotic/synbiotic/probiotic use during study period
* Any medical condition (cardiac, pulmonary, neurological, musculoskeletal, immunological etc.) that would preclude engagement in the yoga intervention
* Any organic gastrointestinal condition (inflammatory bowel disease: Crohn's disease, Ulcerative Colitis, active H. pylori infection, etc.)
* Severe comorbid pain or psychiatric condition requiring recent hospitalization
* Pregnancy, or plans to become pregnant during study period
* Unwilling to participate in study procedures

Primary outcomes:
measure: Changes in Abdominal Pain
timeFrame: 6 weeks
Secondary outcomes:
measure: Baseline Metagenomics
timeFrame: Baseline
measure: Baseline Metabolomics
timeFrame: Baseline
measure: Changes in Metagenomics
timeFrame: 6 weeks
measure: Changes in Metabolomics
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland, Baltimore, School of Nursing
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Kristen R Weaver, PhD
role: PRINCIPAL_INVESTIGATOR
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