Dr. Shailesh Shahi has been awarded a three-year research grant from the National Multiple Sclerosis Society (NMSS) for his project titled, “Determining how obesity alters the gut microbiota to drive the severity of CNS autoimmune inflammatory disease.”

Multiple Sclerosis (MS) is a complex neuroinflammatory autoimmune disease influenced by both genetic and environmental factors. Epidemiological studies show that approximately 50–56% of individuals with MS are overweight or obese. Moreover, obesity is associated with a higher risk of developing MS, more severe disease progression, and earlier disability onset. Over the last five decades, the global rise in obesity rates has paralleled an increase in MS incidence, highlighting the need to explore obesity as a key modifier of disease risk and progression.

Emerging research suggests that the gut microbiota plays a critical role in both MS and obesity. However, the specific contribution of obesity-induced changes in gut microbiota to MS severity remains poorly understood.

Dr. Shahi’s preliminary data, along with findings from other studies, indicate that both diet-induced and genetically predispose obesity lead to an expansion of hydrogen sulfide (H₂S)-producing Proteobacteria in the gut. While low levels of H₂S produced by the host are essential for physiological balance, excessive production by gut bacteria has been linked to systemic and neurological inflammation.

This NMSS-funded project aims to investigate whether obesity-driven shifts in the gut microbiome specifically the overproduction of bacterial H₂S exacerbate MS severity by promoting pro-inflammatory immune responses. Dr. Shahi will explore how these microbial changes influence autoreactive CD4⁺ T cells in the gut, which may migrate to other tissues, including the central nervous system, and intensify disease symptoms.

Importantly, the study will also evaluate whether pharmacologically inhibiting bacterial H₂S production, particularly when combined with current MS disease modifying therapies such as interferon beta or B-cell depletion therapy, can reduce disease severity in the context of obesity. Dr. Shahi’s long-term goal is to develop new therapeutic strategies that improve treatment outcomes for individuals with MS, especially those affected by obesity.

“We’re excited to build on compelling preliminary data that suggest a mechanistic link between gut-derived hydrogen sulfide and increased MS severity. Our hope is that this research will pave the way for microbiota-targeted therapies that can enhance current MS treatment strategies, particularly for patients with obesity.”

This work represents a promising step toward a more personalized, gut-focused approach to MS treatment and may have broader implications for other autoimmune and inflammatory diseases influenced by obesity and the gut microbiome.