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Updated: Sep 9, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Stool Glial Fibrillary Acidic Protein Is Elevated in Progressive Multiple Sclerosis
Luke A Schwerdtfeger1, Federico Montini1,2, Martina Antonini Cencicchio2
1Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Objectives:
The gut microbiota and altered intestinal physiology have been implicated in multiple sclerosis (MS). Enteric glial cells regulate enteric nervous and immune function and express glial fibrillary acidic protein (GFAP) and S100β. Serum GFAP and neurofilament light chain can predict disease worsening; however, no clear markers differentiate relapsing from progressive disease.
Methods:
To investigate enteric glial function in MS, we measured stool GFAP (st-GFAP) using an enzyme-linked immunosorbent assay in 31 healthy controls (HCs), 77 patients with relapsing remitting MS (RRMS), and 53 patients with progressive MS (ProgMS). Participants underwent clinical follow-up at 2 and 5 years after stool donation.
Results:
We found higher st-GFAP levels in patients with ProgMS compared with those with RRMS and HCs. St-GFAP was positively correlated with baseline Expanded Disability Status Scale (EDSS) score, 25-foot walk time, and an increased EDSS score at 2 and 5 years. We found enteric glial hyperplasia in the colonic mucosa of a patient with primary progressive MS, as indicated by GFAP and S100β immunoreactivity, an effect not observed in duodenum tissue in patients with RRMS from our Milan cohort. St-GFAP in patients with ProgMS was negatively associated with Eubacterium hallii.
Discussion:
These exploratory data indicate an altered enteric glial phenotype in patients with ProgMS and suggest that st-GFAP may be a prognostic biomarker.
Insights
Higher levels of stool glial fibrillary acidic protein (GFAP) are found in progressive multiple sclerosis (MS) patients, suggesting it may be a prognostic biomarker for disease worsening.
Area of Science:
- Neuroimmunology
- Gastroenterology
- Microbiome research
Background:
- Multiple sclerosis (MS) is linked to gut microbiota and intestinal changes.
- Enteric glial cells, expressing GFAP and S100β, influence gut nervous and immune systems.
- Current serum markers like GFAP and neurofilament light chain predict worsening but don't distinguish MS subtypes.
Purpose of the Study:
- To investigate enteric glial cell function in MS.
- To assess stool GFAP (st-GFAP) as a potential biomarker differentiating MS disease courses.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) measured st-GFAP in healthy controls (HCs), relapsing-remitting MS (RRMS), and progressive MS (ProgMS) patients.
- Clinical follow-up at 2 and 5 years assessed disease progression.
- Enteric glial hyperplasia was examined via GFAP and S100β immunoreactivity in colonic and duodenal tissue.
Main Results:
- st-GFAP levels were significantly higher in ProgMS compared to RRMS and HCs.
- st-GFAP correlated positively with baseline and longitudinal Expanded Disability Status Scale (EDSS) scores and 25-foot walk time.
- Enteric glial hyperplasia was observed in a primary progressive MS patient's colonic mucosa.
- st-GFAP showed a negative association with *Eubacterium hallii* in ProgMS patients.
Conclusions:
- Exploratory findings suggest an altered enteric glial phenotype in progressive MS.
- st-GFAP may serve as a prognostic biomarker for MS disease progression.
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