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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Gut microbiota and metabolites are linked to disease progression in multiple sclerosis
Luke A Schwerdtfeger1, Federico Montini1, Toby B Lanser1
1Ann Romney Center for Neurologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Abstract:
Progressive multiple sclerosis (MS) is a neurological disease with limited understanding of the biology associated with transition from relapsing to progressive disease. Intestinal microbes and metabolites are altered in MS, but relation to disease progression is largely unknown. We investigate microbiota and metabolites in subjects with stable MS, those who worsened, and in those with relapsing MS who became progressive over 2 years. We find that Eubacterium hallii, Butyricoccaceae, Blautia, and other short-chain fatty-acid-producing microbes have beneficial associations with worsening of disability, 3T magnetic resonance imaging (MRI) measures, cognition, and quality of life, while Alistipes is detrimentally associated. Global metabolomics identified serum and stool metabolites that are altered in progressive MS and in relapsing subjects who transitioned to progressive disease. Most fecal metabolites associated with disease progression are decreased, suggesting a deficiency of protective factors in the gut. Using a unique MS cohort, our findings identify gut microbiome and metabolite pathways influencing progressive MS.
Insights
Gut microbes like Eubacterium hallii and short-chain fatty-acid producers may protect against progressive multiple sclerosis (MS) worsening. Decreased protective gut metabolites suggest a potential deficiency in progressive MS patients.
Area of Science:
- Neuroimmunology
- Microbiome Research
- Metabolomics
Background:
- Progressive multiple sclerosis (MS) pathogenesis remains poorly understood, particularly the transition from relapsing to progressive disease.
- Alterations in intestinal microbiota and metabolites are observed in MS, but their direct role in disease progression is unclear.
Purpose of the Study:
- To investigate the relationship between gut microbiota composition, metabolite profiles, and disease progression in multiple sclerosis (MS).
- To identify specific microbial and metabolic signatures associated with worsening disability, cognitive decline, and quality of life in MS patients.
Main Methods:
- Analysis of fecal microbiota and serum/fecal metabolomics in a cohort of stable MS, worsening MS, and relapsing MS patients transitioning to progressive disease over two years.
- Correlation of microbial and metabolite data with clinical outcomes, including disability scores and 3T magnetic resonance imaging (MRI) measures.
Main Results:
- Beneficial associations were found between short-chain fatty-acid-producing microbes (e.g., Eubacterium hallii, Butyricoccaceae, Blautia) and improved disability, MRI, cognition, and quality of life.
- Alistipes showed detrimental associations with disease progression.
- Decreased fecal metabolites, potentially protective factors, were identified in progressive MS and in patients transitioning to progressive disease.
Conclusions:
- Gut microbiome composition and specific metabolites are linked to multiple sclerosis (MS) disease progression.
- Deficiencies in protective gut metabolites may contribute to the worsening of MS.
- Targeting gut microbiome and metabolite pathways could offer novel therapeutic strategies for progressive MS.
