# Functional Training Mitigates Reduced Circulating Indole‐3‐Lactate Levels in Persons With Relapsing–Remitting Multiple Sclerosis

## TL;DR

Functional training in people with multiple sclerosis increases a brain-protecting compound linked to gut health.

## Contribution

Shows that both short-term and long-term exercise can boost indole-3-lactate levels in MS patients.

## Key findings

- RRMS patients had lower baseline ILA levels compared to healthy controls.
- A 10-week training program increased the ILA/IAA index, indicating a neuroprotective effect.
- A single exercise session acutely raised ILA and ILA/IAA levels.

## Abstract

Indoles are tryptophan (Trp)‐derived metabolites that are produced by the gut microbiota and may influence the gut‐microbiota‐brain axis in multiple sclerosis (MS). Indole‐3‐lactate (ILA) is reduced in persons with MS and improves MS clinical scores in animal models via its anti‐inflammatory remyelinating properties. The ILA/indole‐3‐acetate (IAA) (ILA/AA) index is considered a neuroprotection index. Physical exercise and diet can modify gut microbiota and indole metabolism.

This secondary analysis of a randomized control trial aimed to assess the effects of acute and chronic exercise on serum indoles in relapsing–remitting MS (RRMS). Thirty‐one RRMS patients (≥ 70% session attendance) completed a 10 week multimodal functional training (60 min, 3×/week) vs. a waitlist control group. Blood samples were collected at baseline and compared to a matched healthy control group, and after 10 weeks for the assessment of chronic effects. Additionally, acute effects of a single bout of exercise were assessed with a blood sample before, during, and immediately after one interim training session. Serum indole concentrations were measured using LC–MS/MS.

Baseline indole levels in RRMS patients differed from those of matched healthy controls, and reduced ILA levels were observed. The 10 week intervention increased the ILA/IAA index, while a single exercise bout induced an increase in both ILA and ILA/IAA.

Multimodal functional training over 10 weeks led to an improved ILA/IAA index suggesting a neuroprotective shift in gut microbiota composition, and a single bout acutely increases the circulating level of ILA. Study registration number: DRKS00017091.