Exploring the Impact of Indole-3-Lactate in the Gut-Brain Axis and Multiple Sclerosis: Larissa Jank, MD

WATCH TIME: 5 minutes

"We identified indole-3-lactate (I3LA) as a signaling molecule of the gut brain axis. We found that ILA signals direct from the gut microbiome, so from the bacteria in the gut to the immune system. This finding is interesting for us because it might explain these correlations in dysregulated ILA levels in patients with multiple sclerosis and disease progression.”

Indole-3-lactic acid (I3LA) is a widely known metabolite that plays an important role in tryptophan metabolism. Indole derivatives, including I3LA, are recognized as key contributors to immune cell differentiation and cytokine synthesis through the activation of aryl hydrocarbon receptors, thereby influencing immune modulation.¹ Additionally, these indole derivatives have been implicated in the regulation of allergic responses, which highlights their potential involvement in immune-related pathways in diseases such as multiple sclerosis (MS).

Larissa Jank, MD, postdoctoral researcher, department of neurology, John Hopkins School of Medicine, presented on the link between I3LA and MS in the Whitaker Platform session at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 31 to June 3, in Aurora, Colorado.² In her presentation, she discussed that I3LA not only influences inflammatory cells but also oligodendroglia cells, in particular, which she noted plays an important role in MS disease pathology.

At the meeting, Jank sat down in an interview with NeurologyLive® to provide an overview of her presentation and the main takeaways. She talked about how I3LA mediates its effects on immune, glial, and oligodendroglia cells, and how it acts on specific receptors, altering the cellular metabolism. Jank also spoke about the role of the gut microbiome in breaking down I3LA, potentially influencing its beneficial effects and producing breakdown products with therapeutic properties. In addition, she mentioned some of the limitations of studying substances and mouse models in relation to aging and translation to human patients.

Click here for more coverage of CMSC 2023.

REFERENCES
1. Kim K, Kim H, Sung GY. Effects of Indole-3-Lactic Acid, a Metabolite of Tryptophan, on IL-4 and IL-13-Induced Human Skin-Equivalent Atopic Dermatitis Models. Int J Mol Sci. 2022;23(21):13520. Published 2022 Nov 4. doi:10.3390/ijms232113520
2. Jank L. Indole-3-Lactate, a Gut-Microbiota Derived Metabolite Reduced in Multiple Sclerosis, Dampens Neuroinflammation and Promotes Remyelination. Presented at: 2023 CMSC Annual Meeting; held May 31-June 3; Aurora, CO. SYM13.