The MS-Associated Gut Microbiome
2017
Category: Microbiome
Background: An essential function of the gut microbiota is to
regulate immune responses, including T lymphocyte functions in
health and disease.
Objectives: We hypothesized that gut microbiota contribute to the
pathogenesis of MS.
Methods: We analyzed the microbiome of stool samples from
64 treatment-naive MS patients and 68 healthy controls using
amplicon sequencing of the 16S V4 region of the rRNA gene. We
characterized immune profiles of cultured PBMC in response to
specific bacteria harbored by MS patients.
Results: We found that MS patients exhibited impaired in-vitro
Treg differentiation in response to their own microbiota. No major
shifts in microbial community structure were observed. However,
we were able to identify individual microbial taxa that were significantly
associated with MS and studied their ability to regulate
primary human T lymphocyte differentiation in vitro.
We next conducted in-vitro assays to characterize the functional
properties of the MS gut microbiota. We found that MS-associated
Acinetobacter calcoaceticus was sufficient to reduce Treg
differentiation and increase both Th1 and Th2 differentiation. The
expansion of Th1 lymphocytes was recapitulated by Akkermansia
muciniphila, which was also more abundant in MS patients.
In contrast, Parabacteroidesdistasonis, which was significantly
reduced in MS microbiomes, stimulated CD4+ T lymphocyte
differentiation into a CD25+ IL-10+ regulatory phenotype. Our
results suggest that MS-associated changes in microbiota alter
T lymphocyte differentiation in a complex fashion and likely
through multiple mechanisms.
Finally, microbiota transplants from MS patients into germ-free
mice results in more severe experimental autoimmune encephalomyelitis
and reduced Tregs compared to controls.
Conclusion: This study identifies specific human gut bacteria that
regulate adaptive autoimmune responses, suggesting therapeutic
targeting of the microbiota as a novel treatment for MS.
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