Examining the Impact of a Prebiotic Diet Containing Galactooligosaccharides (GOS) and Polydextrose (PDX) on Inflammation in a Mouse Model of Colitis

Project: Research project

Project Details

Description

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition of the gastrointestinal tract thought be driven by interactions between environmental, microbial and immunologic factors within the gut mucosa of a host with underlying genetic susceptibility, though the specific mechanisms ultimately leading to disease development and progression are incomplete and poorly understood1,2. Alterations in the intestinal microbiome have been described in patients as well as in animal models of IBD3, though further work is needed to elucidate specific microbial changes and underlying biological mechanisms linking the microbiome to disease pathogenesis in order to develop microbial-based therapeutic strategies4.
Interestingly, circadian rhythms have recently emerged as important regulators of the microbiota-gut-brain axis5,6, and a growing body of evidence shows that gut bacterial communities are sensitive to disruptions of the circadian clock system7. Furthermore, disruptions of circadian rhythms and sleep, a key rhythmic output of the circadian clock, have been implicated in IBD: shift workers, who are exposed to chronic circadian rhythm disruption, are at increased risk of developed IBD8. Patients with IBD experience sleep disturbances that may increase the risk for disease flares9. Alterations in the expression of circadian clock genes have been demonstrated in the intestine of IBD patients early in the course of disease10. In animal models of IBD, disruption of sleep and circadian rhythms has been shown to cause earlier disease onset and more severe inflammation11,12. Taken together, these associations and findings suggest a potential role for interactions between the circadian clock system, sleep and the microbiome in the pathogenesis of IBD.
In preliminary work, we along with collaborators have found that a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) leads to improved sleep during experimentally-mediated sleep disruption and recovery as well as protection against stress-induced learning deficits using an acute social defeat stress exposure model. The prebiotic diet also causes significant changes to the fecal microbiome and metabolome, in particular a relative increase in the abundance of the bacterium Parabacteroides distasonis, which positively correlates with sleep measures. These findings of GOS/PDX prebiotic diet-induced microbial changes and enhanced resilience to the physiological challenges of sleep disruption and acute stress exposure raise the question of whether similar protection exists against intestinal inflammation in models of colitis. This proposal will examine whether the GOS/PDX prebiotic diet can reduce inflammation and disease severity in a mouse model of colitis induced by exposure to dextran sodium sulfate (DSS)13. The proposed studies are expected to generate hypotheses for further experiments and to inform approaches in humans involving prebiotic, probiotic and/or other microbial-based approaches to improve gut health in order to ameliorate and possibly treat the underlying symptoms and intestinal inflammation characteristic of IBD.
StatusActive
Effective start/end date7/1/216/30/22

Funding

  • Digestive Health Foundation (Turek AGMT 9/13/21)

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