Impact of a Yoga Intervention on Pain and Multiomics in Participants With IBS
Condition: Irritable Bowel Syndrome; Abdominal Pain
MeSH terms: Irritable Bowel Syndrome; Abdominal Pain
Study type: Interventional

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.
    

Intervention name(s): Yoga Program
Intervention type(s): Other
Intervention description(s): Six-week, twice weekly, 60-minute private yoga program (delivered online/virtually via Zoom).
Allocation: Randomized
Intervention model: Crossover Assignment
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.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Irritable bowel syndrome; IBS; Yoga; Microbiome; Abdominal pain; Metagenome; Metabolome