Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis

Lindsay Devolder; Ayla Pauwels; Ann Van Remoortel; Gwen Falony; Sara Vieira-Silva; Guy Nagels; Jacques De Keyser; Jeroen Raes; Marie B D'Hooghe

doi:10.1080/19490976.2023.2180316

Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis

Gut Microbes. 2023 Jan-Dec;15(1):2180316. doi: 10.1080/19490976.2023.2180316.

Authors

Lindsay Devolder^{1

2

3}, Ayla Pauwels^{1

2

3

4

5}, Ann Van Remoortel⁵, Gwen Falony^{1

2

6}, Sara Vieira-Silva^{1

2

6}, Guy Nagels^{3

4

7}, Jacques De Keyser^{3

4}, Jeroen Raes^{1

2}, Marie B D'Hooghe^{3

4

5}

Affiliations

¹ Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
² Center for Microbiology, VIB Center for Microbiology, VIB, Leuven, Belgium.
³ Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium.
⁴ Department of Neurology, Universitair Ziekenhuis Brussel, Jette, Belgium.
⁵ National Multiple Sclerosis Center, Melsbroek, Belgium.
⁶ Institute of Medical Microbiology and Hygiene, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
⁷ St. Edmund Hall, University of Oxford, Oxford, UK.

Abstract

Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice.

Trial registration: ClinicalTrials.gov NCT04929145.

Keywords: Bacteroides 2; EDSS-Plus; gut microbiome; long-term disability worsening; multiple sclerosis; neurofilament light chain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gastrointestinal Microbiome*
Humans
Multiple Sclerosis*

Associated data

ClinicalTrials.gov/NCT04929145

Grants and funding

This work was co-funded by the Vlaams instituut Biotechnologie; the Rega Institute for Medical Research, KU Leuven, and an FWO research grant (G038318N) awarded to MD and JR; Research Foundation Flanders.