Table 1.

Published research examining the effects of probiotics intake on immune and inflammatory markers in animal and human models of MS

Author	Sample	Supplementation	Duration	Measurements	Findings
Salehipour et al., 2017 [35]	MOG-induced EAE in Female C57BL/6 mice, 8–10 weeks old, n = 8 per group	Treatment (T) groups: T1: L. plantarum T2: B. animalis T3: Both of probiotics. 109 CFU	22 days	- CD4+, CD25+, Foxp3+, IL-10, IL-4, TGF-β, GATA3 - IFN-γ, IL-17, IL-6, T-bet, and ROR-γt	T1, T2, and T3 (particularly in T3): - Mitigation of EAE in mice through motivating polarization of CD4+ T-cells toward T-reg by induction of anti-inflammatory cytokines and transcription factors and inhibition of pro-inflammatory cytokines, thereby suppressing autoreactive T-cells proliferation and leukocyte infiltration into CNS
Secher et al., 2017 [51]	MOG-induced EAE in male C57/BL6Jmice, 8–12 weeks old, n = 30–40 per group	T groups: T1: E. coli Nissle T2: archetypal. 108 CFU	30 days	- Z0–1, Claudin-8, Reg3γ, Reg3β - CD4+, IFN-γ, IL-17, and TNF-α	- Reduced the severity of EAE induced by immunization with the MOG35-55 peptides - Decreased secretion of inflammatory cytokines and an increased production of the anti-inflammatory cytokine by autoreactive CD4 T-cells, in peripheral lymph nodes and CNS - Increased numbers of MOG-specific CD4+ T-cells in the periphery contrasting with severely reduced numbers in the CNS - Repaired intestinal permeability dysfunction
Kobayashi et al., 2012 [52]	PLP-induced EAE in SJL/J and MOG-induced EAE in C57BL/6 Female mice, 7 weeks old, n = 15 per group	- T group: L. casei 0.6–1.2 × 109 CFU	50 days	- IL-17 and IFN-γ, IL-10 protein levels and mRNA, - CD4+, CD25+, CD8+ T-reg cells	- Non-significant neurological symptoms or histopathological changes of the spinal cord (SC) in either model - Improve neurological symptoms in the PLP-induced EAE in SJL/J mouse Unregulated IL-17 production by antigen-stimulated lymphocytes of draining lymph nodes on day 7 - Enhanced production of IL-10 and an increase in the percentage of CD4+CD25+ T-reg - Strong expression of IL-17 mRNA on day 12, but this expression was not enhanced by LcS administration
Kwon et al., 2013 [53]	MOG-induced EAE in C57BL/6mice 6–8 weeks old, n = 10 per group	The IRT 5 probiotics contains 108 CFU/g of each strain: L. casei, L. acidophilus, L. reuteni, B. bifidum, Streptococcus thermophiles. (final 5 × 108 CFU)	30 days	IL-4 (Th2) and IL-10 (Th2) and CD4+ T-cells, Foxp3+, IL-2 - CD3+, Gr1+ or/and CD11b+ monocyte, B220+ B cells - Th1/Th17; IFN-γ, TNFα and IL-17 protein levels and mRNA, IL-1β	- Prophylactic and therapeutic effects - A T-cell-mediated inflammatory autoimmune disease of the CNS - Pretreatment of IRT5 probiotics expressively suppressed EAE development - Delayed the disease onset of EAE - Inhibited the pro-inflammatory Th1/Th17 polarization, while inducing IL-10+ producing or/and Foxp3+ T-reg, both in the peripheral immune system and at the site of inflammation
Lavasani et al., 2010 [54]	MOG-induced EAE in Female C57BL/6mice, 8–10 weeks, n = 5 per group	T1: L. paracasei, DSM 13434; T2: L. plantarum, DSM 15312; T3: L. plantarum, DSM 15313; T4: L. paracasei, PCC, 101; T5: L. delbrueckii, subsp. L. bulgaricus, DSM 20081. T6: T1, T2, and T3. 109 CFU	25 days	- Th2 type cytokines, - IL-4, IL-10, TGF-β1 CD25, CD4+T-cells IL-27, TNF-α, IFN-γ, IL-17	- T1, T2, and T3 reduced inflammation in CNS and autoreactive T-cell responses - T1 and T2 induced CD4+CD25+Foxp3+ T-reg in MLNs and enhanced production of serum TGF- β1, while T3 increased serum IL-27 levels - T6 suppressed the progression and reversed the clinical and histological signs of EAE - The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood
Kouchaki et al., 2016 [50]	18 to 55 years, n = 30 per group	probiotic capsule: L. acidophilus L. casei B. bifidum L. fermentum 2 × 109 CFU	12 weeks	B cell- hs-CRP	Decreased serum insulin, hs-CRP- improve B cell function concentration
Salami et al., 2019	20 to 60 years n = 24 per group	Probiotic capsules: B. infantis, B. lactis, L. reuteri, L. casei, L. plantarum and L. fermentum 2 × 109 CFU	16 weeks	- IL-6, TNF-α, hs-CRP - IL-10	- Reduction in some of inflammatory markers - Increase in IL-10 and nitric oxide levels

Abbreviations: CD cluster of differentiation, CFU colony-forming unit, CNS central nervous system, EAE experimental autoimmune encephalomyelitis, GATA3 GATA binding protein 3, GM-CSF granulocyte-macrophage colony-stimulating factor, hs-CRP high-sensitivity C-reactive protein, IL interleukin, IFN-γ interferon gamma, MLNs mesenteric lymph nodes, MOG myelin oligodendrocyte glycoprotein, PLP proteolipid protein. ROR-γt RAR-related orphan receptor gamma, Th T-helper cells, TNFα tumor necrosis factor alpha, TGF-β transforming growth factor beta; T-reg regulatory T-cell