Selected Clostridia Strains from The Human Microbiota and their Metabolite, Butyrate, Improve Experimental Autoimmune Encephalomyelitis.
Laura Calvo-BarreiroHerena EixarchThais CornejoCarme CostaMireia CastilloLeyre MestreCarmen GuazaMaría Del Carmen Martínez-CuestaTakeshi TanoueKenya HondaJuan José González-LópezXavier MontalbanCarmen EspejoPublished in: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2021)
Gut microbiome studies in multiple sclerosis (MS) patients are unravelling some consistent but modest patterns of gut dysbiosis. Among these, a significant decrease of Clostridia cluster IV and XIVa has been reported. In the present study, we investigated the therapeutic effect of a previously selected mixture of human gut-derived 17 Clostridia strains, which belong to Clostridia clusters IV, XIVa, and XVIII, on the clinical outcome of experimental autoimmune encephalomyelitis (EAE). The observed clinical improvement was related to lower demyelination and astrocyte reactivity as well as a tendency to lower microglia reactivity/infiltrating macrophages and axonal damage in the central nervous system (CNS), and to an enhanced immunoregulatory response of regulatory T cells in the periphery. Transcriptome studies also highlighted increased antiinflammatory responses related to interferon beta in the periphery and lower immune responses in the CNS. Since Clostridia-treated mice were found to present higher levels of the immunomodulatory short-chain fatty acid (SCFA) butyrate in the serum, we studied if this clinical effect could be reproduced by butyrate administration alone. Further EAE experiments proved its preventive but slight therapeutic impact on CNS autoimmunity. Thus, this smaller therapeutic effect highlighted that the Clostridia-induced clinical effect was not exclusively related to the SCFA and could not be reproduced by butyrate administration alone. Although it is still unknown if these Clostridia strains will have the same effect on MS patients, gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a beneficial effect on MS clinical course.
Keyphrases
- multiple sclerosis
- end stage renal disease
- regulatory t cells
- chronic kidney disease
- ejection fraction
- newly diagnosed
- endothelial cells
- immune response
- mass spectrometry
- escherichia coli
- ms ms
- fatty acid
- metabolic syndrome
- gene expression
- spinal cord injury
- prognostic factors
- high resolution
- skeletal muscle
- white matter
- toll like receptor
- single cell
- insulin resistance
- patient reported
- optical coherence tomography
- induced pluripotent stem cells
- high glucose
- atomic force microscopy
- high speed