Impact of a Yoga Intervention on Pain and Multiomics in Participants With IBS

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.