Orally Ingested Probiotics, Prebiotics, and Synbiotics as Countermeasures for Respiratory Tract Infections in Non-elderly Adults: A Systematic Review and Meta-analysis

Document Type

Journal Article

Publication Date



Advances in nutrition (Bethesda, Md.)




common cold; coronavirus; dietary supplement; fermentable fiber; gut microbiome; influenza; respiratory illness; respiratory infection


BACKGROUND: The impact of gut microbiota-targeted interventions on the incidence, duration, and severity of respiratory tract infections (RTI) in non-elderly adults, and factors moderating any such effects, are unclear. OBJECTIVES: This systematic review and meta-analysis aimed to determine the effects of orally ingested probiotics, prebiotics, and synbiotics versus placebo on RTI incidence, duration, and severity in non-elderly adults, and to identify potential sources of heterogeneity. METHODS: Studies were identified by searching CENTRAL, PubMed, Scopus, and Web of Science up to December 2021. English-language peer-reviewed publications of randomized, placebo-controlled studies that tested an orally ingested probiotic, prebiotic or synbiotic intervention of any dose for ≥ 1 week in adults 18-65 yr were included. Results were synthesized using intention-to-treat and per protocol random effects meta-analysis. Heterogeneity was explored by sub-group meta-analysis and meta-regression. Risk of bias (RoB) was assessed using the Cochrane RoBv.2 tool for randomized trials. RESULTS: Forty-two manuscripts reporting effects of probiotics (n = 38), prebiotics (n = 2), synbiotics (n = 1) or multiple -biotic types (n = 1) were identified (n = 9,179 subjects). Probiotics reduced the risk of experiencing ≥ 1 RTI (relative risk = 0.91 [95%CI: 0.84, 0.98] P = 0.01), and total days (rate ratio = 0.77 [0.71, 0.83] P < 0.001), duration (Hedges's g = -0.23 [-0.39, -0.08] P = 0.004) and severity (Hedges's g = -0.16 [-0.29, -0.03] P = 0.02) of RTI. Effects were relatively consistent across different strain combinations, doses and durations, though reductions in RTI duration were larger with fermented dairy as the delivery matrix, and beneficial effects of probiotics were not observed in physically active populations. Overall RoB was rated as "some concerns" for most studies. CONCLUSIONS: Orally ingested probiotics, relative to placebo, modestly reduce the incidence, duration and severity of RTI in non-elderly adults. Physical activity and delivery matrix may moderate some of these effects. Whether prebiotic and synbiotic interventions confer similar protection remains unclear due to few relevant studies. PROSPERO registration: CRD42020220213.


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