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Table 1 Published research examining the effects of probiotics intake on immune and inflammatory markers in animal and human models of MS

From: Immunomodulatory and anti-inflammatory effects of probiotics in multiple sclerosis: a systematic review

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

  1. 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