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Oral gut microbiota manipulation by antibiotics and probiotics influences neuroimmune responses in a progressive model of multiple sclerosis

AuthorsMestre, Leyre ; Carrillo-Salinas, F. J.; Mecha, Miriam ; Feliú, Ana; Espejo, Carmen; Villar, L.M.; Guaza, Carmen
KeywordsImmune Function
Microglial cells
Myelin diseases
Issue Date12-Jul-2019
CitationXIV European Meeting on Glial Cells in Health and disease in Porto, Portugal, 10-13 July, 2019
AbstractOn the last decade, cumulative evidence reported a relationship between gut microbiota and MS. Both gut microbiota eradication and probiotic administration attenuated the clinical severity of autoimmune models of MS (EAE). However, an unresolved question is to what extent manipulations of gut microbiota affect the course of the disease. Particularly, the relevance of gut microbiota on the progressive forms of MS is a field little explored. Here, we addressed how gut microbiota manipulation by antibiotics and/or probiotics influences the establishment of clinical symptomatology in the TMEV-IDD model of progressive MS. Experimental groups are showed in the scheme below. Main results reveal that motor disability can be prevented in TMEV-mice treated with antibiotic mix (ABX) during the presyntomatic stage (55-70dpi); the attenuation of motor deficits was maintained in mice treated with ABX until day 85dpi (symptomatic phase). The beneficial effect was less powerful in ABX-mice that stopped the treatment at day 70pi and gut microbiota started recolonization in the presence of the probiotic (Vivomixx) for 15 days. Accordingly, the increased regulatory CD39+ T and CD5CD1high B cells in the CNS of ABX- treated mice was reverted after ABX cessation an probiotic administration. Likewise, the proinflammatory cytokines IL-1β and TNF-α increased and the anti-inflammatory cytokines IL-4 and IL-10 decreased in the CNS of TMEV mice that interrupted oral ABX and received Vivomixx. In this scenario, microglia also undergoes morphological changes upon the different microbiota challenges. Mainly, cells show transitioning morphology from thin cell bodies with numerous branched extensions to round, amoeboid cells with fewer branches in TMEV-ABX mice increasing the percentage of Iba-1 staining area versus TMEV mice. Astrocytes also show morphological changes under microbiota manipulation. We also addressed the therapeutic effect of oral Vivomixx on the symptomatic stage. Similarly to ABX, the probiotic treatment improves motor disability of TMEV-mice; however, the underlying mechanisms were different: Thus, regulatory B cells acquired more prominence and microglial cells spread more branches than observed in the CNS of ABX-TMEV-mice. Our results support the relevance of the gut microbiota-CNS axis on neurodegenerative diseases particularly, on the progressive forms of MS.
Appears in Collections:(IC) Comunicaciones congresos
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