. 2022 Jan 5;35(1):e00338-20. doi: 10.1128/CMR.00338-20

TABLE 3.

Microbial intervention in multiple sclerosis

Source	Study design	Sample size (n)	Study population	Microbial strains	Study duration	Key finding(s)
Fecal microbiota transplantation
Makkawi et al., 2018 (447)	Human (SPMS) Case report	1 participant	A 61-yr-old woman with MS	Not mentioned.	>10 yrs	Amelioration of the Expanded Disability Status Scale (EDSS).
Cekanaviciute et al., 2017 (123)	Preclinical animal study	142 participants	71 MS patients not undergoing treatment and 71 healthy controls	Human MS or healthy fecal microbiota transplantation	70 days	Immunoregulatory effects in MS via healthy human gut microbiota transplantation.
Berer et al., 2017 (120)	Preclinical animal study	38 participants	20 humanized transgenic 6-wk-old, germ-free RR mice MS-FMT; 18 humanized transgenic 6-wk-old, germ-free RR mice HT-FMT	The transplantation of fecal samples was from selected healthy and MS twin pairs.	12 wks	MS-FMT contributed or spontaneous autoimmune encephalomyelitis in mouse models.

Probiotics
Salehipour et al., 2017 (448)	Randomized, placebo-controlled, double-blind trial	24 participants	MOG-induced EAE in female C57BL/6 mice, 8 to 10 wks old, n = 8 per group	Treatment (T) groups: T1, L. plantarum; T2, B. animalis; T3, both probiotics; 10⁹ CFU	22 days	T1, T2, and remarkably 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.
						Inhibition of proinflammatory cytokines, resulting in the suppression of leukocyte infiltration, proliferation of autoreactive T cells into CNS.
Salami et al., 2019 (449)	Randomized, placebo-controlled, double-blind trial	58 participants	20 to 60 yrs, n = 24 per group	Probiotic capsules containing Bifidobacterium infantis, B. lactis, Lactobacillus reuteri, L. casei, L. fermentum, L. plantarum, and 2 × 10⁹ CFU.	16 wks	Decrease in several inflammatory markers, such as hs-CRP levels and IL-6.
Salami et al., 2019 (449)	Randomized, placebo-controlled, double-blind trial	58 participants	20 to 60 yrs, n = 24 per group		16 wks	Enhancement in levels of nitric oxide and IL-10.
Secher et al., 2017 (450)	Preclinical animal study	60 to 80 participants	MOG-induced EAE in male C57/BL6Jmice, 8 to 12 wks old, n = 30–40 per group	The archetypal K-12 E. coli strain MG1655 and the probiotic E. coli Nissle 1917 (ECN)	30 days	EAE progression and severity is correlated with variation in the intestinal barrier function is associated with the impact of probiotic treatment on improving the intestinal permeability may be beneficial in controlling CNS pathogenesis and neuroinflammation.