Impact of Indole 3-Lactate Supplementation in Multiple Sclerosis Animal Models: Larissa Jank, MD

WATCH TIME: 4 minutes

"In our new finding, [indole 3-lactate] supplementation not only blocks neuroinflammation and enhances remyelination but also restores this imbalance of circulatory metabolites."

Metabolites originating from the gut microbiome, such as indoles, exhibit dysregulation in multiple sclerosis (MS). In MS, research shows there is a notable decrease in circulating indole 3-lactate (ILA), having a more pronounced reduction in progressive forms compared with relapsing-remitting disease. Additionally, the elevated ratio of indole 3-acetate to ILA in MS is associated with increased disease severity. In a recent preclinical study, findings showed that supplementation of ILA reduced neuroinflammation and promoted remyelination in MS.¹ These results identified a novel mechanism by which gut metabolite imbalance in MS impacts neuroinflammation and suggests ILA supplementation is a potential restoring treatment.

The findings were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, in West Palm Beach, Florida, by lead author Larissa Jank, MD, in a session on emerging concepts in MS. In the study, investigators used 2 animal models induced by subcutaneous immunization with a myelin peptide with adjuvants, and cuprizone-induced toxic demyelination, to assess ILA's effect on central nervous system immune infiltration, reactive gliosis and remyelination. At the conclusion of the study, findings showed that ILA restored the MS associated indole metabolite imbalance by reducing circulating levels of the remyelination-blocking metabolite IAA.

Jank, postdoctoral researcher, department of neurology, Johns Hopkins School of Medicine, sat down in an interview with NeurologyLive® at the forum to discuss why ILA supplementation impacts circulating indole 3-acetate levels in MS. In addition, she talked about how the oxidative pathways for ILA and indole 3-acetate differ, and its implications that it may have for MS severity. Furthermore, Jank spoke about the next steps with the ongoing microbiome studies in aiming to reveal more knowledge about the impact of ILA on gut microbiome composition and function.

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REFERENCES
1. Jank L, Singh S, Dhukhwa A, et al. Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation. Presented at ACTRIMS Forum 2024; February 29 to March 2; West Palm Beach, Florida. S1.3.