Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials

Abstract

Background: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking.

Methods: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies.

Results: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events.

Conclusions: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Keywords: Autoimmune disease; Gut microbiota-based therapies; Meta-analysis; Probiotics; Systematic review.

Fig. 1

Flow diagram

Fig. 2

Risk of bias summary

Fig. 3

Risk of bias graph

Fig. 4

Outcomes of SLE and LN (A SLEDAI; B IgG level)

Fig. 5

Outcomes of RA (A DAS28; B tender joint counts; C swollen joint counts)

Fig. 6

Outcomes of MS: EDSS

Fig. 7

Outcomes of T1DM: HbA1c

Fig. 8

Outcomes of ulcerative colitis (A Endoscopy Score; B Ineffective rate; C Disease activity; D Relapse rate; E ESR; F: CRP)

Fig. 9

Adverse events of gut microbiota-based therapies for ulcerative colitis

Fig. 10

Potential molecular mechanism of probiotics in the treatment of autoimmune diseases (The mechanism is summarized from [, , , , –, –158]. AhR: aryl hydrocarbon receptor; CNS: central nervous system; FFARs: free fatty acid receptors; GLP1: glucagon-like protein-1; GPRs: G-binding protein receptors; H2: histamine receptor 2; PYY: peptide tyrosine tyrosine; SCFAs: short-chain fatty acids)