The role of superoxide dismutase SOD-1 in microbe-gut-brain interaction

This NIH-funded investigation titled, "The role of superoxide dismutase SOD-1 in microbe-gut-brain interaction," a five-year, $1.6 million study probing how an intestinal gene, SOD-1, may mediate communication between gut microbes and the nervous system and contribute to neurodegenerative disease. Chang, a researcher at Rowan University School of Osteopathic Medicine who arrived from SUNY Binghamton, is motivated both scientifically and personally: a family history of ALS informs his interest in how mutations in SOD-1 can disrupt normally healthy gut-brain relationships and potentially trigger or influence diseases such as ALS, Parkinson's, and Alzheimer's. The project centers on understanding how a mutated form of SOD-1, first identified in the 1990s, alters interactions among the gut microbiome, intestinal physiology, immune responses, and brain function. Chang emphasizes that a healthy gut microbiome supports immunity and has broader effects on psychological status, aging, dementia risk, and neurodegeneration.

This study seeks to trace mechanisms by which specific microbes or microbe-derived signals influence brain physiology, and how SOD-1 mutations in the gut may change that signaling in ways that promote disease. By examining the intestinal expression and function of SOD-1, the research aims to identify new genetic, molecular, and protein-level layers of regulation that link gut microbes to neural outcomes. The work will address how the presence of SOD-1 mutations in a subset of the population relates to clinical disease expression, noting that familial ALS-hereditary cases tied to mutations like SOD-1 accounts for roughly ten percent of ALS cases, while most cases remain sporadic without a clearly defined etiology. Chang's approach positions the gut microbiome as a potentially transformative axis for therapeutic discovery: if specific microbial interactions or SOD-1-dependent pathways can be linked causally to neurodegeneration, they could yield novel targets for interventions aimed at improving ALS and related conditions. The study is framed as foundational research to map connections between intestinal genes, microbial communities, and brain physiology rather than as an immediate cure; nevertheless,

The researchers hope that uncovering these pathways will eventually inform therapies that improve patient outcomes. The NIH grant supports multi-year investigation into these mechanisms, with the goal of elucidating how an intestinal gene like SOD-1 can tip the balance from a healthy microflora-“brain relationship toward pathological processes that culminate in neurodegenerative disease. This project integrates genetics, microbiology, neurobiology, and clinical perspective, reflecting Chang's commitment to translating insights about gut-brain biology into potential strategies for understanding and, ultimately, mitigating diseases such as ALS.