Objective: To investigate the effect of hyperbaric oxygen therapy (HBOT) on gut microbiota in a preclinical model of PD.

Background: Humans have coevolved with complex communities of gut microbiota that control immune function locally and systemically, and modulate immune system development and responses. Microbiota distortions along the brain-gut axis associated with intestinal inflammation contribute to α-syn misfolding, initiation and progression of PD. Treatments being developed in our lab such as adoptive cellular therapy (ACT) using antigen specific T cells, and Hyperbaric Oxygen therapy (HBO) have the potential to modulate α-syn pathology, restore gut microbiota homeostasis and slow disease progression.

Method: M83^+/- mice, expressing the A53T mutation found in a subset of human patients with familial PD, received α-syn preformed fibrils (PFFs) at 8 weeks of age. HBO treatments started 4 weeks after PFF injections. Animals received HBO every day for 1h, at 2ATA for 8 weeks after PFF injections. Fecal pellets were collected at baseline prior to start of HBO, and the end of HBO treatment and were frozen for 16S rDNA microbiota analysis.

Results: In animals that were treated with HBO, we observed less overall microbiota distortions, based on alpha-diversity measures. Previously we have demonstrated that treatments such as ACT can result in an enrichment of potentially beneficial bacteria such as Bifidobacterium which has been associated with gut homeostasis and neuroprotection. HBO can modulate microbiota composition in traumatic brain injury and spinal cord injury, hence we examined (N=6/group) the relationship between gut microbiota composition in response to HBO in a PD model (M83^+/- + PFFs). We found that HBO prevented PFF-associated distortion in microbiota diversity (Shannon index). We also found a statistically significant increase in Prevotellaceae (p<0.02) associated with HBO, potentially associated with reduced levels of inflammatory markers. Interestingly, a reduction in Prevotellaceae has been observed in PD patients. Prevotellaceae can produce SCFAs, and have been shown to inversely correlate with symptoms in PD patients.

Conclusion: Microbiota changes resulting from HBO can influence gut inflammation. Thus, microbiota targeting interventions may offer new alternative avenues for managing GI symptoms and slow progression in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hyperbaric-oxygen-therapy-for-parkinsons-disease-via-modulation-of-gut-microbiota/