The immune-metabolite axis is the bidirectional, complex communication between the immune system and metabolites produced by host cells and the gut microbiota. Both byproducts play key roles in regulating inflammation, acting through signaling networks that involve various immune cell receptors and epigenetic pathways. Understanding this axis offers potential therapeutic avenues to treat a wide range of chronic inflammatory conditions by modulating metabolite levels through dietary interventions, probiotics, or pharmacological agents.
“Microbes digest carbohydrates that are indigestible by us, and the resulting metabolites are important for maintaining a healthy gut lining. The resulting metabolites also enter the circulatory system and affect the liver, muscles, and, importantly, immune cells. Thus, microbes may contribute to the beneficial effects of health-promoting diets,” according to Renuka Nayak, MD, PhD, Assistant Professor, University of California, San Francisco.
During the Sunday, October 26, session Immune-Metabolite Axis: How Microbial and Host Byproducts Drive Inflammation, Dr. Nayak will discuss therapeutic approaches to treat rheumatoid arthritis (RA) using short-chain fatty acids (SCFA). The session will take place from 10:30–11:30 a.m. in Room W192A-C of McCormick Place. Robert Keskey, MD, PhD, Assistant Professor of Surgery, University of Louisville, whose work focuses on the role of microbial metabolites in host-pathogen interactions, will discuss microbial metabolites that have shown promise in regulating sepsis.
Along with her colleagues, Dr. Nayak’s research on identical twins who are discordant for RA found that the twin with RA had significantly lower concentrations of fecal butyrate and propionate. SCFA-producing bacteria were also decreased in the RA twin. This suggests that low levels of SCFAs may contribute to the development or progression of RA.
“SCFAs like butyrate and propionate are known to have anti-inflammatory properties,” she said. “They can promote the development of regulatory T cells, which help suppress the inflammatory immune response. This has been observed in both animal studies and human trials.”
Dr. Nayak and her fellow researchers have studied whether butyrate supplementation can affect the gut microbiome and immune system in patients with new-onset RA. Early findings showed that butyrate supplementation increased gut microbial diversity and the abundance of certain bacteria linked to a better response to the RA medication methotrexate.
Dr. Nayak’s team discovered that methotrexate responders had higher fecal butyrate concentrations at baseline. Butyrate supplementation in combination with methotrexate was also found to increase gut bacterial diversity. This suggests that the gut microbiome, and SCFAs in particular, may influence how effective standard RA treatments are. Research has also shown that SCFAs can help mitigate osteoclast-mediated arthritic bone erosion, highlighting their potential role in protecting bone health in the context of arthritis.
On-demand access to recorded presentations will be available to registered attendees of ACR Convergence following the annual meeting through October 31, 2026.
Don’t Miss a Session
If you weren’t able to make it to a live session during ACR Convergence 2025 — or you want to revisit a session from the annual meeting — make plans to watch the replay. All registered participants receive on-demand access to scientific sessions after the meeting through October 31, 2026.