Gut Microbial Interactions Reveal a New Mechanism for Suppressing Neuroinflammation
Professor Bong-Soo Kim
Department of Nutritional Science and Food Management
A collaborative research team led by Professor Bong-Soo Kim of the Department of Nutritional Science and Food Management at Ewha Womans University and Professor Yoon-Kyung Lee of Soonchunhyang University have identified a mechanism by which metabolites generated through gut microbial interactions can reach the brain and suppress neuroinflammation.
The findings provide new insight into the connection between the gut microbiome, immune system, and brain and may contribute to the development of microbiome-based therapeutic strategies for autoimmune diseases such as multiple sclerosis (MS). The study was published online in July in Experimental & Molecular Medicine (Impact Factor: 17.5; top 2.1% in JCR).
MS is an autoimmune disease in which immune cells attack the brain and spinal cord, causing inflammation and neurological damage. Although various treatments are available, limitations including immune-related adverse effects and disease recurrence highlight the need for new therapeutic approaches. The gut microbiome has recently gained attention as a key regulator of the gut–brain axis, but the mechanisms by which microbial interactions generate metabolites that influence neuroinflammation remain poorly understood.
Through analyses of large-scale cohorts from diverse populations, the research team observed a consistent reduction of the genus Veillonella in individuals with MS. Among several human-derived Veillonella ratti strains examined, V. ratti MHL0042 showed a particularly strong ability to alleviate disease severity. The researchers therefore administered MHL0042 to mice with experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, to investigate its biological effects and mechanism of action.
MHL0042 reshaped the disrupted gut microbial ecosystem by promoting microbial interactions throughout the intestinal tract. It reduced bacteria carrying pldA, a gene involved in phosphatidylethanolamine metabolism, resulting in increased levels of dioleoyl phosphatidylethanolamine (DOPE).
Importantly, elevated DOPE was detected not only in the intestine but also systemically and in the central nervous system. MHL0042 treatment reduced CNS inflammation, including CD4⁺ IFN-γ⁺ T cells and activated microglia in the spinal cord. Administration of DOPE alone also alleviated EAE symptoms and suppressed microglial activation, demonstrating that DOPE is an important mediator of the protective effects induced by MHL0042.
This study demonstrates how gut microbial interactions can generate a bioactive metabolite that acts beyond the intestine to regulate neuroinflammation. Future clinical studies will be needed to evaluate the safety and efficacy of V. ratti MHL0042 and DOPE in humans and to determine how individual differences in gut microbiome composition influence DOPE production.
Professor Bong-Soo Kim said, “Our study reveals a new mechanism by which metabolites generated through microbial interactions within the gut microbiome can regulate immune responses in the brain. These findings provide a scientific basis for developing microbiome-based personalized therapies, therapeutic adjuvants, and dietary interventions for multiple sclerosis and other neuroinflammatory diseases.”