Exopolysaccharides in immunomodulation of ulcerative colitis: A systematic review and meta-analysis of randomized controlled trials in an animal model

Exopolysaccharides (EPS) are produced by microorganisms and can serve as crucial immunomodulatory agents. However, their effectiveness in regulating inflammatory cytokines and inducing remission of ulcerative colitis (UC), a chronic and non-specific inflammatory ailment that affects around 5 million adults worldwide, remains largely unknown. The objective of this study was to conduct a thorough analysis and evaluation of the effects of exopolysaccharides on the immune system in animals with ulcerative colitis in randomized preclinical trials. The literature was performed according to the protocol registered in PROSPERO (CRD42022348361) and PRISMA guidelines. PubMed, Science Direct, Scopus, Web of Science, LiLacs, ScieLo, Cochrane and TripDatabase databases were reviewed for randomized preclinical studies that met the inclusion and exclusion criteria defined between January 2013 and July 2022. Methodological quality was assessed by SYRCLE “Risk of Bias” (RoB) and meta-analysis was performed with Review Manager 5.3 software using a random effects model. A total of six studies met the inclusion criteria and were at low risk of bias. Meta-analysis showed that EPS significantly decreased both pro-inflammatory cytokines: Tumor necrosis factor alpha (TNF-α) (SMD= -375.31, 95% CI (-628.23–122.39), p= 0.004); Interferon-gamma (IFN-γ) (SMD= -144.19, 95% CI (-261–26.54) p= 0.02); Interleukin-6 (IL-6) (SMD= -481.78, CI 95% (-771.00–192.56) p=0.001), how to recover colon length (SMD: 9.24, CI 95 % (4.38 - 14.09), p = 0.0002) and disease activity index (DAI) (SMD: -13.29, 95% CI(-19.04–7.55), p=0.00001), while they showed no effects against the anti-inflammatory cytokines IL-10 (SDM: 683.59, 95% CI (-86.41-1453.60, p = 0.08) and IL-4 (SMD: 16.05, CI 95% (-52.27-84.37), p=0.65). The meta-analysis results indicated that EPS could be an alternative or adjuvant treatment for UC, mainly regulating of pro-inflammatory agents. However, studies of intracellular signaling are needed to offer more elucidative evidence.