ABSTRACT
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.
ABSTRACT
INTRODUCTION: Respiratory tract infections (RTI), such as those caused by influenza viruses and, more recently, the severe acute respiratory syndrome coronavirus-2, pose a significant burden to military health care systems and force readiness. The gut microbiota influences immune function, is malleable, and may provide a target for interventions aiming to reduce RTI burden. This narrative review summarizes existing evidence regarding the effectiveness of probiotics, prebiotics, and synbiotics, all of which are gut microbiota-targeted interventions, for reducing the burden of RTI in military-relevant populations (i.e., healthy non-elderly adults). MATERIALS AND METHODS: A systematic search strategy was used to identify recent meta-analyses and systematic reviews of randomized controlled trials conducted in healthy non-elderly adults which examined effects of probiotics, prebiotics, or synbiotics on the incidence, duration, and/or severity of RTI, or on immune responses to vaccinations against viruses that cause RTI. Relevant randomized controlled clinical trials not included in those reports were also identified. RESULTS: Meta-analyses and multiple randomized controlled trials have demonstrated that certain probiotic strains may reduce the incidence, duration, and/or severity of RTI and improve immune responses to vaccination against RTI-causing pathogens in various populations including healthy non-elderly adults. Fewer randomized controlled trials have examined the effects of prebiotics or synbiotics on RTI-related outcomes in healthy non-elderly adults. Nevertheless, some studies conducted within that population and other populations have observed that certain prebiotics and synbiotics reduce the incidence, duration, and/or severity of RTI or improve immune responses to vaccinations against RTI-causing viruses. However, across all product classes, not all product formulations have shown benefit, and most have not been tested in multiple randomized controlled trials in military-relevant populations. CONCLUSION: Dietary supplementation with certain gut microbiota-targeted interventions, and certain probiotics in particular, may provide viable strategies for reducing RTI-related illness in military personnel. Research in military populations is warranted to fully understand the magnitude of any military health and cost benefits, and to establish definitive recommendations for use.