Effects of Lactobacillus casei Strain T2 (IBRC-M10783) on the Modulation of Th17/Treg and Evaluation of miR-155, miR-25, and IDO-1 Expression in a Cuprizone-Induced C57BL/6 Mouse Model of Demyelination

Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: a comprehensive review

“…Four human studies were structured as double-blind, placebo-controlled RCTs, 60 , 61 , 63 , 64 and the remaining two were prospective cohort studies. 46 , 47 , The animal models of MS included EAE ( n = 27), cuprizone- 45 , 71 or gliotoxin-induced demyelination, 52 and Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). 43 …”

“…lactis BB12 T4 : B. animalis subsp. LMG S-28195 T5 : T1+ T2 T6 : T3+ T4 Each 2 × 10 9 CFU/300 µL orally C : vehicle Proph & Thera 15 doses over 3 wks (5 doses pre-EAE) CD : ↓ EAE incidence & median score at peak (T1-T6); ↓ myelin loss, astrocytosis, & spinal cord immune cell infiltration (T5/T6); delayed EAE onset (T1,T2, T5, T6); dose-response relationship observed with T5/T6 IM : ↓ proliferative response to MBP, IFN-γ, TNF-α, IL-17 (T5/T6); ↑ TGF-β, IL-16 (T5/T6) MM : NA MC : NA Baken et al 73 UN M Lewis rats 6–8 wko n = 8/g gpSCH-induced EAE T : L. casei strain Shirota, 1 mL of 1 × 10 9 CFU/mL C : 1 mL saline/peptone Proph & Thera Daily for 35 d (starting 8 d pre-EAE) CD : ↓ body weight; ↑ EAE incidence, duration, CDS, & CDI; earlier EAE onset IM : NA MM : NA MC : NA Gharehkhani Digehsara et al 71 UN F C57BL6 mice 8–10 wko Cuprizone (4 wks) T1 : L. casei 4 wks, cuprizone 4 wks T2 : Cuprizone 4 wks, L. casei 4 wks T3 : Cuprizone 4 wks, L. casei 4 wks w/ Vitamin D3 (20 IU/d) C1 : L. casei 4 wks, 1 × 10 9 CFU/mL C2 : Cuprizone 4 wks, 0.2% w/w All admin orally C3 : normal control Proph & Thera CD : more normal & significant Y-maze alternation behavior (T1-T3) IM : ↓ IL-17 (T1-T3), T3 more pronounced; ↑ TGF-β (T1-T3) MM : NA MC : ↓ expression of IDO gene & miR-155 (T1-T3, C2); ↑ expression of miR-25 (C2), trending in T1-T3 Kobayashi et al 68 UN M & F Lewis rats 7 wko & 2 wko n = 8/g gpSCH- or gpMBP-induced EAE T1 : L. casei strain S...…”

“…More studies investigated the effects of Lactobacillus spp. [48][49][50]52,53,59,67,68,[71][72][73][74][75][76] and probiotic combinations [43][44][45]48,50,53,69 rather than Bifidobacterium spp. [51][52][53]68 and E. coli Nissle 1917, 54,55 and just a single study utilized E. faecium.…”

“…51,59,68,[72][73][74][75] It should also be noted that only four of the studies were classified as high quality, all of which reported positive results with probiotics. 44,45,50,53 The majority of studies reported favorable secondary immunological findings, with elevated levels of anti-inflammatory cytokines (IL-10, IL-4, TGFβ) 43,48,50,53,55,59,69,71,74 and CD4+ CD25+ FoxP3 + Tregs 44,50,54,55,69,74 and reduced levels of proinflammatory cytokines (IL-17, IL-1, IL-6, TNF-α, IFN-γ), 43,48,50,53,55,67,69,71,75 chemokines (CCL3, CCL4, CXCL5, CXCL13), 49 and T H 1 and T H 17 cells. 43,54,55,67,69,74,75 Multiple Lactobacillus spp.…”

miR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review

“…The results of recent studies based on the EAE model induced by cuprizone (a copper chelator molecule that affects oligodendrocytes) confirmed that decreasing expression of miR-155-3p can prevent microglia activation, myelin damage, and MS progression [ 90 , 91 ]. Analysis of miR-155 expression carried out on a mouse model allowed revealing the effect of the probiotic bacteria, Lactobacillus casei, on the recovery of demyelinated animals by regulating the immune response [ 92 ]. Another research conducted on the cuprizone-induced demyelination model evaluated the miRNAs expression and predicted their target genes according to the micro-RNA database (miRDB).…”