Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome

Sukirth M Ganesan; Meeta Yadav; Sudeep Ghimire; Peter C Lehman; Apurva J Patel; Sydney Woods; Heena Olalde; Jemmie Hoang; Mishelle Paullus; Catherine Cherwin; Christine Gill; Tracey Cho; Ashutosh K Mangalam

doi:10.1002/acn3.70212

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Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome

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Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome

Sukirth M Ganesan, Meeta Yadav, Sudeep Ghimire, Peter C Lehman, Apurva J Patel, Sydney Woods, Heena Olalde, Jemmie Hoang, Mishelle Paullus, Catherine Cherwin, …

Annals of clinical and translational neurology, Vol.13(2), pp.256-269

02/2026

DOI: 10.1002/acn3.70212

PMCID: PMC12883679

PMID: 41051180

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Abstract

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurological impairment. While the gut microbiota's role in MS is extensively studied, the association between the oral microbiota and MS remains underexplored, particularly in North American cohorts. This study aimed to investigate the microbiota (bacterial) composition as well as functional pathways and immune profiles of the oral cavity in 60 patients with relapsing-remitting MS (RRMS), stratified by treatment status, compared to 44 healthy controls (HC). Unstimulated saliva was collected for genomic DNA extraction and salivary cytokine quantification. Oral bacterial composition and diversity were analyzed using 16S rRNA sequencing, with functional pathways inferred using PICRUSt2. Salivary cytokine levels were measured via multiplex immunoassays. LEfSe and random forest models identified key discriminatory taxa, and correlations between microbiota and cytokines were assessed using Spearman's rank analysis. RRMS patients exhibited distinct microbial communities compared to HC and a higher Bacteroidota to Firmicutes ratio. Key taxa such as Campylobacter, Lachnoanaerobaculum, and Porphyromonas were enriched in RRMS. Functional profiling revealed 49 differentially abundant pathways, including the enrichment of lipopolysaccharide biosynthesis in MS. Elevated levels of IFN-γ, IL-6, and other cytokines correlated with the altered microbiome. IL-21, elevated in HC, correlated with anti-inflammatory pathways, suggesting a protective role in immune homeostasis. This study provides, for the first time, insights into oral microbiome-host interactions in North American RRMS patients, underscoring the interplay between microbial dysbiosis, functional pathways, and immune dysregulation. The oral microbiome shows potential as a biomarker for MS-related immune alterations.

Cytokines

Inflammation

Multiple Sclerosis

oral microbiome

dysbiosis

UIOWA OA Agreement

Details

Title: Subtitle: Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome
Creators: Sukirth M Ganesan - University of Iowa
Meeta Yadav - University of Iowa
Sudeep Ghimire - University of Iowa
Peter C Lehman - University of Iowa
Apurva J Patel - University of Iowa
Sydney Woods - Department of Periodontics, University of Iowa College of Dentistry and Dental Clinics, Iowa City, Iowa, USA
Heena Olalde - University of Iowa
Jemmie Hoang - University of Iowa
Mishelle Paullus - University of Iowa
Catherine Cherwin - University of Iowa
Christine Gill - University of Iowa
Tracey Cho - University of Iowa
Ashutosh K Mangalam - University of Iowa
Resource Type: Journal article
Publication Details: Annals of clinical and translational neurology, Vol.13(2), pp.256-269
DOI: 10.1002/acn3.70212
PMID: 41051180
PMCID: PMC12883679
NLM abbreviation: Ann Clin Transl Neurol
ISSN: 2328-9503
eISSN: 2328-9503
Publisher: Wiley
Grant note: Carver Trust Department of Pathology, University of Iowa 10.13039/100000002 / National Institute of Health, USA 1P20NR018081-01 / NINR NIH HHS University of Iowa Environmental Health Sciences Research Center 5T90DE023520 / NIH HHS 1I01CX002212 / US department of Veterans Affairs 1RO1AI137075 / National Institute of Allergy and Infectious Diseases, USA T32AI007260 / NIH HHS
Language: English
Electronic publication date: 10/06/2025
Date published: 02/2026
Academic Unit: Neurology; Pathology; Iowa Neuroscience Institute; Nursing; Medicine Administration; Periodontics
Record Identifier: 9984969243602771

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