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
Affiliations
Lindsay Devolder
Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Ayla Pauwels
Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Ann Van Remoortel
National Multiple Sclerosis Center, Melsbroek, Belgium
Gwen Falony
Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Sara Vieira-Silva
Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Guy Nagels
Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium
Jacques De Keyser
Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium
Jeroen Raes
Laboratory of Molecular Bacteriology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Marie B. D’Hooghe
Center for Neurosciences, Vrije Universiteit Brussel, Jette, Belgium
ABSTRACTPredicting 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.
