Efficacy and safety of gastrointestinal microbiome supplementation for allergic rhinitis: A systematic review and meta-analysis with trial sequential analysis

Allergic rhinitis (AR) is a non-infective chronic inflammatory disease of nasal mucosa.To evaluate the efficacy and safety of gastrointestinal microbiome supplementation (GMS) for patients with allergic rhinitis (AR), concerning improvement on symptoms and signs, laboratory outcomes, quality of life, and medication scores.Five English databases were searched up to Dec 12th, 2022. Probiotics, prebiotics, and synbiotics were main therapies or adjuvants in experimental groups. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.4 Software, with meta-influence analyses, subgroup-analyses, meta-regression, and publication bias performed for exploration of heterogeneity by Stata V.14. Trial sequential analyses were performed by TSA 0.9, and quality of the results was accessed through the GRADE-pro GDT.Finally, extracted from 53 articles, 65 RCTs involving 3,634 participants with sound worldwide representativeness were included. Primary results showed better improvement in GMS groups on TNSS (WMD=1.05, P for WMD=0.004, 95%CI:0.34 to 1.76), overall nasal condition (WMD=1.25, P for WMD<0.001, 95%CI:0.90 to 1.61), overall quality of life (WMD=6.16, P for WMD<0.001, 95%CI:4.92 to 7.40) and medication score (WMD=0.42, P for WMD=0.42, 95%CI:-0.06 to 0.90).However, GMS groups were inferior than the controls concerning reduction on serum total IgE (WMD=-1.81) and ratios of serum Th1/Th2 (WMD=-1.06). Meta-regressions suggested significant (p<0.05) variations of the effects in some comparisons. In addition, results of sub-group analyses firstly revealed potential influence between final results and the variables above. Instantly after intervention, the GRADE levels of evidence were sound, including "High ⨁⨁⨁⨁" in 10, "Moderate ⨁⨁⨁◯" in 33, and "Low ⨁⨁◯◯" in nine comparisons. However, overall certainties decreased obviously during follow-ups.Overall, our pooled results firstly revealed that GMS yielded acceptable benefits for patients with AR compared with controls with sound certainties, after balancing the benefits and harms.