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

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

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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.

Originele taal-2	English
Artikelnummer	2180316
Tijdschrift	Gut Microbes
Volume	15
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1080/19490976.2023.2180316
Status	Published - 2023

Bibliografische nota

Funding Information:
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. We thank all study participants for their valuable contribution. We sincerely appreciate all who provided logistic support for sample collection (nurses and health practitioners in the National MS Center as well as Annick Van Merhaegen-Wieleman and Tatjana Reynders in University Hospital Brussels). We are grateful for the support of Chloë Verspecht, Duyen Nguyen, Leen Rymenans, Lindsey De Commer and other members of the Raes Lab for assistance in laboratory work and logistics or participation in helpful discussions. We thank Kristin Verbeke for facilitating measurements of moisture content in fecal samples.

Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.

Copyright:
Copyright 2023 Elsevier B.V., All rights reserved.

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10.1080/19490976.2023.2180316Licentie: CC BY-NC

94743280Final published version, 2,71 MBLicentie: CC BY-NC

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title = "Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis",

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.",

keywords = "Humans, Multiple Sclerosis, Gastrointestinal Microbiome, Bacteroides 2, EDSS-Plus, gut microbiome, long-term disability worsening, neurofilament light chain",

author = "Lindsay Devolder and Ayla Pauwels and {Van Remoortel}, Ann and Gwen Falony and Sara Vieira-Silva and Guy Nagels and {De Keyser}, Jacques and Jeroen Raes and D'Hooghe, {Marie B}",

note = "Funding Information: 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. We thank all study participants for their valuable contribution. We sincerely appreciate all who provided logistic support for sample collection (nurses and health practitioners in the National MS Center as well as Annick Van Merhaegen-Wieleman and Tatjana Reynders in University Hospital Brussels). We are grateful for the support of Chlo{\"e} Verspecht, Duyen Nguyen, Leen Rymenans, Lindsey De Commer and other members of the Raes Lab for assistance in laboratory work and logistics or participation in helpful discussions. We thank Kristin Verbeke for facilitating measurements of moisture content in fecal samples. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. Copyright: Copyright 2023 Elsevier B.V., All rights reserved.",

year = "2023",

doi = "10.1080/19490976.2023.2180316",

language = "English",

volume = "15",

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AU - Pauwels, Ayla

AU - Van Remoortel, Ann

AU - Falony, Gwen

AU - Vieira-Silva, Sara

AU - Nagels, Guy

AU - De Keyser, Jacques

AU - Raes, Jeroen

AU - D'Hooghe, Marie B

N1 - Funding Information: 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. We thank all study participants for their valuable contribution. We sincerely appreciate all who provided logistic support for sample collection (nurses and health practitioners in the National MS Center as well as Annick Van Merhaegen-Wieleman and Tatjana Reynders in University Hospital Brussels). We are grateful for the support of Chloë Verspecht, Duyen Nguyen, Leen Rymenans, Lindsey De Commer and other members of the Raes Lab for assistance in laboratory work and logistics or participation in helpful discussions. We thank Kristin Verbeke for facilitating measurements of moisture content in fecal samples. Publisher Copyright: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. Copyright: Copyright 2023 Elsevier B.V., All rights reserved.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

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SN - 1949-0976

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ER -

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

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