Short‐chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset

Objective The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged...

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Published in:Annals of clinical and translational neurology Vol. 11; no. 1; pp. 169 - 184
Main Authors: Schoeps, Vinicius A., Zhou, Xiaoyuan, Horton, Mary K., Zhu, Feng, McCauley, Kathryn E., Nasr, Zahra, Virupakshaiah, Akash, Gorman, Mark P., Benson, Leslie A., Weinstock‐Guttman, Bianca, Waldman, Amy, Banwell, Brenda L., Bar‐Or, Amit, Marrie, Ruth Ann, Domselaar, Gary, O'Mahony, Julia, Mirza, Ali I., Bernstein, Charles N., Yeh, E. Ann, Casper, T. Charles, Lynch, Susan V., Tremlett, Helen, Baranzini, Sergio, Waubant, Emmanuelle
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01.01.2024
John Wiley and Sons Inc
Wiley
Subjects:
Animals
Body mass index
Breastfeeding & lactation
Canada
Case-Control Studies
Child
Confounding (Statistics)
Cytomegalovirus
Encephalomyelitis, Autoimmune, Experimental
Ethnicity
Fatty acids
Fatty Acids, Volatile
Guardians
Humans
Microbiota
Multiple Sclerosis
Pediatrics
Canada
United States > US
San Francisco California
California
ISSN:2328-9503, 2328-9503
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Summary:Objective The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric‐onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. Methods A multicenter case–control study in which 35 pediatric‐onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self‐reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co‐occurrence networks and for predicting functional abundances based on marker gene sequences. Results Two microbial co‐occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short‐chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family‐level findings from an independent Canadian‐US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. Interpretation Our results suggest that short‐chain fatty acid producers may be important contributors to multiple sclerosis onset.
Bibliography:These authors contributed equally to this work.
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ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.51944