Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters

The pathogenesis of multiple sclerosis (MS), an autoimmune
disease affecting the brain and spinal cord, remains poorly understood.
Patients with MS typically present with recurrent episodes of neurological
dysfunctions such as blindness, paresis, and sensory disturbances. Studies on
experimental autoimmune encephalomyelitis (EAE) animal models have led to a
number of testable hypotheses including a hypothetical role of altered gut
microbiota in the development of MS. To investigate whether gut microbiota in
patients with MS is altered, we compared the gut microbiota of 20 Japanese
patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy
Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the
HC18 subjects repeatedly provided fecal samples over the course of months (158
samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by
using a high-throughput culture-independent pyrosequencing method provided
evidence of a moderate dysbiosis in the structure of gut microbiota in patients
with MS. Furthermore, we found 21 species that showed significant differences
in relative abundance between the MS20 and HC40 samples. On comparing MS
samples to the 158 longitudinal HC18 samples, the differences were found to be
reproducibly significant for most of the species. These taxa comprised
primarily of clostridial species belonging to Clostridia clusters XIVa and IV
and Bacteroidetes. The phylogenetic tree analysis revealed that none of the
clostridial species that were significantly reduced in the gut microbiota of
patients with MS overlapped with other spore-forming clostridial species
capable of inducing colonic regulatory T cells (Treg), which prevent
autoimmunity and allergies; this suggests that many of the clostridial species
associated with MS might be distinct from those broadly associated with
autoimmune conditions. Correcting the dysbiosis and altered gut microbiota
might deserve consideration as a potential strategy for the prevention and
treatment of MS.

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