Dr. Shailesh Shahi has been awarded a three-year, $999,265 grant from the Department of Defense Multiple Sclerosis Research Program (DoD-MSRP) for his project titled “Impact of Obesity-Driven Gut Microbiota Alterations on Multiple Sclerosis.”

Multiple sclerosis (MS) is a complex neuroinflammatory disease influenced by both genetic and environmental factors. Among these, obesity is a major modifiable environmental risk factor that worsens MS severity and reduces the effectiveness of disease-modifying therapies. However, the mechanisms by which obesity contributes to MS treatment resistance and increased disease severity remain unclear.

Recent research has underscored the gut microbiota as a critical mediator in the etiopathogenesis of both obesity and MS. Dr. Shahi’s published work and preliminary findings using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS reveal that diet-induced obesity leads to significant changes in gut microbial composition specifically, an enrichment of hydrogen sulfide (H₂S)-producing bacteria, upregulation of microbial H₂S metabolic pathways, and increased fecal H₂S levels. These obesity-associated increases in H₂S-producing bacteria are accompanied by heightened pro-inflammatory immune responses, supporting a potential mechanistic link between gut microbiota alterations and the exacerbation of MS pathology.

This DoD-funded project aims to investigate whether inhibiting bacterial H₂S production alone or in combination with existing MS therapies can reduce inflammation and thereby mitigate MS severity in the context of obesity.

Upon completion of this study, Dr. Shahi expects to gain critical insights into how obesity-induced gut microbiota changes influence MS progression. These findings are anticipated to lay the groundwork for future translational research assessing the clinical potential of targeting bacteria-derived H₂S as a novel therapeutic approach for MS in obese individuals an underserved patient population for whom current therapies are often less effective.

Ultimately, this work represents a significant step toward Dr. Shahi’s long-term goal of developing microbiota-targeted, personalized treatment strategies for improving outcomes in MS patients affected by obesity.