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. 2022 Aug 24;8(8):CD006895.
doi: 10.1002/14651858.CD006895.pub4.

Probiotics for preventing acute upper respiratory tract infections

Yunli Zhao  1 , Bi Rong Dong  2 , Qiukui Hao  1
Affiliations

Probiotics for preventing acute upper respiratory tract infections

Yunli Zhao et al. Cochrane Database Syst Rev. .

Abstract

Background: Probiotics are live micro-organisms that may give a beneficial physiological effect when administered in adequate amounts. Some trials show that probiotic strains can prevent respiratory infections. Even though our previously published review showed the benefits of probiotics for acute upper respiratory tract infections (URTIs), several new studies have been published. This is an update of a review first published in 2011 and updated in 2015.

Objectives: To assess the effectiveness and safety of probiotics (any specified strain or dose), compared with placebo or no treatment, in the prevention of acute URTIs in people of all ages, at risk of acute URTIs.

Search methods: We searched CENTRAL (2022, Issue 6), MEDLINE (1950 to May week 2, 2022), Embase (1974 to 10 May 2022), Web of Science (1900 to 10 May 2022), the Chinese Biomedical Literature Database, which includes the China Biological Medicine Database (from 1978 to 10 May 2022), the Chinese Medicine Popular Science Literature Database (from 2000 to 10 May 2022), and the Master's Degree Dissertation of Beijing Union Medical College Database (from 1981 to 10 May 2022). We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials on 10 May 2022.

Selection criteria: We included individual randomised controlled trials (RCTs) and cluster-RCTs comparing probiotics with placebo or no treatment to prevent acute URTIs. The participants were children, adults, or the elderly in the community, care facilities, schools, or hospitals. Our main outcomes were the number of participants diagnosed with URTIs (at least one event and at least three events), the incidence rate (number of cases/person year) of acute URTIs, and the mean duration of an episode of URTIs. Our secondary outcomes were the number of participants who were absent from childcare centre, school, or work due to acute URTIs; the number of participants who used prescribed antibiotics for acute URTIs; and the number of participants who experienced at least one adverse event from probiotics. We excluded studies if they did not specify acute respiratory infections as 'upper'; studies with more than 50% of participants vaccinated against influenza or other acute URTIs within the last 12 months; and studies with significantly different proportions of vaccinated participants between the probiotics arm and the placebo or no treatment arm.

Data collection and analysis: Two review authors independently assessed the eligibility of trials and extracted data using standard Cochrane methodological procedures. We analysed both intention-to-treat and per-protocol data and used a random-effects model. We expressed results as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

Main results: We included 23 individual RCTs and one cluster-RCT. As one of the individual RCTs did not report outcomes in a usable way, we could only meta-analyse data from 23 trials, involving a total of 6950 participants including children (aged from one month to 11 years old), adults (mean age 37.3), and older people (mean age 84.6 years). One trial reported 22.5% flu-vaccine participants within the last 12 months, and 25.4% flu-vaccine participants during the intervention. Probiotics were more likely to be given with milk-based food in children; administered in powder form in adults; and given with milk-based food or in capsules in the elderly. Most of the studies used one or two strains (e.g. Lactobacillus plantarum HEAL9, Lactobacillus paracasei (8700:2 or N1115)) and 109 or 1011 colony-forming units (CFU)/day of probiotics for more than three months. We found that probiotics may reduce the number of participants diagnosed with URTIs (at least one event) (RR 0.76, 95% CI 0.67 to 0.87; P < 0.001; 16 studies, 4798 participants; low-certainty evidence); likely reduce the number of participants diagnosed with URTIs (at least three events) (RR 0.59, 95% CI 0.38 to 0.91; P = 0.02; 4 studies, 763 participants; moderate-certainty evidence); may reduce the incidence rate (number of cases/person year) of URTIs (rate ratio 0.82, 95% CI 0.73 to 0.92, P = 0.001; 12 studies, 4364 participants; low-certainty evidence); may reduce the mean duration of an episode of acute URTIs (MD -1.22 days, 95% CI -2.12 to -0.33; P = 0.007; 6 studies, 2406 participants; low-certainty evidence); likely reduce the number of participants who used prescribed antibiotics for acute URTIs (RR 0.58, 95% CI 0.42 to 0.81; P = 0.001; 6 studies, 1548 participants; moderate-certainty evidence); and may not increase the number of participants who experienced at least one adverse event (RR 1.02, 95% CI 0.90 to 1.15; P = 0.79; 8 studies, 2456 participants; low-certainty evidence). Evidence showing a decrease in the number of people absent from childcare centre, school, or work due to acute URTIs with probiotics is very uncertain (RR 0.14, 95% CI 0.03 to 0.59; 1 study, 80 participants; very low-certainty evidence). Adverse events from probiotics were minor, and most commonly gastrointestinal symptoms, such as vomiting, flatulence, diarrhoea, and bowel pain. AUTHORS' CONCLUSIONS: Overall, we found that probiotics were better than placebo or no treatment in preventing acute URTIs.

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Conflict of interest statement

Yunli Zhao: has declared that they have no conflict of interest. Bi Rong Dong: has declared that they have no conflict of interest. Qiukui Hao: has declared that they have no conflict of interest.

Figures

1
1
Chinese Biomedical Literature Database search strategy.
2
2
Study flow diagram.
3
3
Risk of bias graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
Contour‐enhanced funnel plot of comparison: intention‐to‐treat analysis: probiotics versus placebo ‐ primary outcome measures, outcome: the number of participants who were diagnosed with acute URTIs: at least 1 event.
6
6
Contour‐enhanced funnel plot of comparison: intention‐to‐treat analysis: probiotics versus placebo ‐ primary outcome measures, outcome: the incidence rate of acute URTIs.
1.1
1.1. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 1: The number of participants who were diagnosed with acute URTIs: at least 1 event (age)
1.2
1.2. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 2: The number of participants who were diagnosed with acute URTIs: at least 1 event (treatment dose)
1.3
1.3. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 3: The number of participants who were diagnosed with acute URTIs: at least 1 event (treatment duration)
1.4
1.4. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 4: The number of participants who were diagnosed with acute URTIs: at least 1 event (type of comparator)
1.5
1.5. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 5: The number of participants who were diagnosed with acute URTI: at least 3 events (age)
1.6
1.6. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 6: The number of participants who were diagnosed with acute URTI: at least 3 events (treatment dose)
1.7
1.7. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 7: The number of participants who were diagnosed with acute URTI: at least 3 events (treatment duration)
1.8
1.8. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 8: The number of participants who were diagnosed with acute URTI: at least 3 events (type of comparator)
1.9
1.9. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 9: The incidence rate of acute URTIs (age)
1.10
1.10. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 10: The incidence rate of acute URTIs (treatment dose)
1.11
1.11. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 11: The incidence rate of acute URTIs (treatment duration)
1.12
1.12. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 12: The incidence rate of acute URTIs (type of comparator)
1.13
1.13. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 13: The mean duration of an episode of acute URTIs (age)
1.14
1.14. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 14: The mean duration of an episode of acute URTIs (treatment dose)
1.15
1.15. Analysis
Comparison 1: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 15: The mean duration of an episode of acute URTIs (treatment duration)
2.1
2.1. Analysis
Comparison 2: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ time off from childcare centre, school, or work, Outcome 1: The number of participants who were absent from childcare centre, school, or work due to acute URTIs
3.1
3.1. Analysis
Comparison 3: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 1: The number of participants who used antibiotics for acute URTIs (age)
3.2
3.2. Analysis
Comparison 3: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 2: The number of participants who used antibiotics for acute URTIs (treatment dose)
3.3
3.3. Analysis
Comparison 3: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 3: The number of participants who used antibiotics for acute URTIs (treatment duration)
3.4
3.4. Analysis
Comparison 3: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 4: The number of participants who used antibiotics for acute URTIs (type of comparator)
4.1
4.1. Analysis
Comparison 4: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 1: The number of participants who experienced at least 1 adverse event (age)
4.2
4.2. Analysis
Comparison 4: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 2: The number of participants who experienced at least 1 adverse event (treatment dose)
4.3
4.3. Analysis
Comparison 4: Intention‐to‐treat analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 3: The number of participants who experienced at least 1 adverse event (treatment duration)
5.1
5.1. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 1: The number of participants who were diagnosed with acute URTIs: at least 1 event (age)
5.2
5.2. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 2: The number of participants who were diagnosed with acute URTIs: at least 1 event (treatment dose)
5.3
5.3. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 3: The number of participants who were diagnosed with acute URTIs: at least 1 event (treatment duration)
5.4
5.4. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 4: The number of participants who were diagnosed with acute URTIs: at least 1 event (type of comparator)
5.5
5.5. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 5: The number of participants who were diagnosed with acute URTIs: at least 3 events (age)
5.6
5.6. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 6: The number of participants who were diagnosed with acute URTIs: at least 3 events (treatment dose)
5.7
5.7. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 7: The number of participants who were diagnosed with acute URTIs: at least 3 events (treatment duration)
5.8
5.8. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 8: The number of participants who were diagnosed with acute URTIs: at least 3 events (type of comparator)
5.9
5.9. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 9: The incidence rate of acute URTIs (age)
5.10
5.10. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 10: The incidence rate of acute URTIs (treatment dose)
5.11
5.11. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 11: The incidence rate of acute URTIs (treatment duration)
5.12
5.12. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 12: The incidence rate of acute URTIs (type of comparator)
5.13
5.13. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 13: The mean duration of an episode of acute URTIs (age)
5.14
5.14. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 14: The mean duration of an episode of acute URTIs (treatment dose)
5.15
5.15. Analysis
Comparison 5: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ primary outcome measures, Outcome 15: The mean duration of an episode of acute URTIs (treatment duration)
6.1
6.1. Analysis
Comparison 6: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ time off from childcare centre, school, or work, Outcome 1: The number of participants who experienced time off from childcare centre, school, or work due to acute URTIs
7.1
7.1. Analysis
Comparison 7: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 1: The number of participants who used antibiotics for acute URTIs (age)
7.2
7.2. Analysis
Comparison 7: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 2: The number of participants who used antibiotics for acute URTIs (treatment dose)
7.3
7.3. Analysis
Comparison 7: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 3: The number of participants who used antibiotics for acute URTIs (treatment duration)
7.4
7.4. Analysis
Comparison 7: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ prescribed antibiotics for acute URTIs, Outcome 4: The number of participants who used antibiotics for acute URTIs (type of comparator)
8.1
8.1. Analysis
Comparison 8: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 1: The number of participants who experienced at least 1 adverse event (age)
8.2
8.2. Analysis
Comparison 8: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 2: The number of participants who experienced at least 1 adverse event (treatment dose)
8.3
8.3. Analysis
Comparison 8: Per‐protocol analysis: probiotics versus placebo or no treatment ‐ adverse events, Outcome 3: The number of participants who experienced at least 1 adverse event (treatment duration)
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Gerasimov 2016 {published data only}
    1. Gerasimov SV, Ivantsiv VA, Bobryk LM, Tsitsura OO, Dedyshin LP, Guta NV, et al. Role of short-term use of L. acidophilus DDS-1 and B. lactis UABLA-12 in acute respiratory infections in children: a randomized controlled trial. European Journal if Clinical Nutrition 2016;70(4):463-9. [DOI: 10.1038/ejcn.2015.171] - DOI - PubMed
Gil‐Campos 2012 {published data only}
    1. Gil-Campos M, López MÁ, Rodriguez-Benítez MV, Romero J, Roncero I, Linares MD, et al. Lactobacillus fermentum CECT 5716 is safe and well tolerated in infants of 1-6 months of age: a randomized controlled trial. Pharmacological Research 2012;65(2):231-8. - PubMed
Gleeson 2010 {published data only}
    1. Gleeson M, Bishop NC, Oliveira M, Tauler P. Daily probiotic's (Lactobacillus casei Shirota) reduction of infection incidence in athletes. International Journal of Sport Nutrition & Exercise Metabolism 2011;21(1):55-64. - PubMed
Gleeson 2012 {published data only}
    1. Gleeson M, Bishop NC, Oliveira M, McCauley T, Tauler P, Lawrence C. Effects of a Lactobacillus salivarius probiotic intervention on infection, cold symptom duration and severity, and mucosal immunity in endurance athletes. International Journal of Sport Nutrition and Exercise Metabolism 2012;22(4):235-42. - PubMed
Guillemard 2010 {published data only}
    1. Guillemard E, Tondu F, Lacoin F, Schrezenmeir J. Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial. British Journal of Nutrition 2010;103(1):58-68. - PubMed
Gutierrez‐Castrellon 2014 {published data only}
    1. Gutierrez-Castrellon P, Lopez-Velazquez G, Diaz-Garcia L, Jimenez-Gutierrez C, Mancilla-Ramirez J, Estevez-Jimenez J, et al. Diarrhea in preschool children and Lactobacillus reuteri: a randomized controlled trial. Pediatrics 2014;133(4):e904-9. - PubMed
Hatakka 2001 {published data only}
    1. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 2001;322(1298):1327-9. - PMC - PubMed
Hatakka 2007 {published data only}
    1. Hatakka K, Blomgren K, Pohjavuori S, Kaijalainen T, Poussa T, Leinonen M, et al. Treatment of acute otitis media with probiotics in otitis-prone children - a double-blind, placebo-controlled randomised study. Clinical Nutrition 2007;26(3):314-21. - PubMed
Haywood 2014 {published data only}
    1. Haywood BA, Black KE, Baker D, McGarvey J, Healey P, Brown RC. Probiotic supplementation reduces the duration and incidence of infections but not severity in elite rugby union players. Journal of Science and Medicine in Sport 2014;17(4):356-60. - PubMed
Hishiki 2020 {published data only}
    1. Hishiki H, Kawashima T, Tsuji NM, Ikari N, Takemura R, Kido H, et al. A double-blind, randomized, placebo-controlled trial of heat-killed Pediococcus acidilactici K15 for prevention of respiratory tract infections among preschool children. Nutrients 2020;12(7):1989. [DOI: 10.3390/nu12071989] - DOI - PMC - PubMed
Hojsak 2015 {published data only}
    1. Hojsak I, Tokić Pivac V, Močić Pavić A, Pasini AM, Kolaček S. Bifidobacterium animalis subsp. lactis fails to prevent common infections in hospitalized children: a randomized, double-blind, placebo-controlled study. American Journal of Clinical Nutrition 2015;101(3):680-4. [DOI: 10.3945/ajcn.114.102004] - DOI - PubMed
Hojsak 2016 {published data only}
    1. Hojsak I, Močić Pavić A, Kos T, Dumančić J, Kolaček S. Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers - randomized, double blind, placebo-controlled study. Clinical Nutrition 2016;35(3):587-91. [DOI: 10.1016/j.clnu.2015.05.004] - DOI - PubMed
Hor 2018 {published data only}
    1. Hor YY, Lew LC, Lau ASY, Ong JS, Chuah LO, Lee YY, et al. Probiotic Lactobacillus casei Zhang (LCZ) alleviates respiratory, gastrointestinal & RBC abnormality via immuno-modulatory, anti-inflammatory & anti-oxidative actions. Journal of Functional Foods 2018;44:235-45. [DOI: 10.1016/j.jff.2018.03.017] - DOI
Kekkonen 2007 {published data only}
    1. Kekkonen RA, Vasankari TJ, Vuorimaa T, Haahtela T, Julkunen I, Korpela R. The effect of probiotics on respiratory infections and gastrointestinal symptoms during training in marathon runners. International Journal of Sport Nutrition & Exercise Metabolism 2007;17(4):352-63. - PubMed
Kloster Smerud 2008 {published data only}
    1. Kloster Smerud H, Ramstad Kleiveland C, Roll Mosland A, Grave G, Birkeland SE. Effect of a probiotic milk product on gastrointestinal and respiratory infections in children attending day-care. Microbial Ecology in Health and Disease 2008;20(2):80-5.
Kosek 2019 {published data only}
    1. Kosek MN, Peñataro-Yori P, Paredes-Olortegui M, Lefante J, Ramal-Asayag C, Zamora-Babilonia M, et al. Safety of Lactobacillus Reuteri DSM 17938 in healthy children 2-5 years of age. Pediatric Infectious Disease Journal 2019;38(8):e178-80. [DOI: 10.1097/INF.0000000000002267] - DOI - PMC - PubMed
Kukkonen 2008 {published data only}
    1. Kukkonen K, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al. Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial. Pediatrics 2008;122(1):8-12. - PubMed
Kumpu 2012 {published data only}
    1. Kumpu M, Kekkonen RA, Kautiainen H, Järvenpää S, Kristo A, Huovinen P, et al. Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial. European Journal of Clinical Nutrition 2012;66(9):1020-3. - PubMed
Kumpu 2013 {published data only}
    1. Kumpu M, Lehtoranta L, Roivainen M, Rönkkö E, Ziegler T, Söderlund-Venermo M. The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care. Journal of Medical Virology 2013;85(9):1632-8. - PubMed
Lau 2018 {published data only}
    1. Lau AS, Yanagisawa N, Hor YY, Lew LC, Ong JS, Chuah LO, et al. Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children. Beneficial Microbes 2018;9(1):61-70. [DOI: 10.3920/BM2017.0063] - DOI - PubMed
Lefevre 2015 {published data only}
    1. Lefevre M, Racedo SM, Ripert G, Housez B, Cazaubiel M, Maudet C, et al. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study. Immunity & Ageing 2015;12:24. [DOI: 10.1186/s12979-015-0051-y] - DOI - PMC - PubMed
Lehtoranta 2012 {published data only}
    1. Lehtoranta L, Söderlund-Venermo M, Nokso-Koivisto J, Toivola H, Blomgren K, Hatakka K, et al. Human bocavirus in the nasopharynx of otitis-prone children. International Journal of Pediatric Otorhinolaryngology 2012;76(2):206-11. - PMC - PubMed
Leyer 2009 {published data only}
    1. Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC. Probiotic effects on cold and influenza-like symptom incidence and duration in children. Pediatrics 2009;124(2):e172-9. - PubMed
Li 2014 {published data only}
    1. Li F, Jin X, Liu B, Zhuang W, Scalabrin D. Follow-up formula consumption in 3- to 4-year-olds and respiratory infections: an RCT. Pediatrics 2014;133(6):e1533-40. [DOI: 10.1542/peds.2013-3598] - DOI - PubMed
Lin 2009 {published data only}
    1. Lin JS, Chiu YH, Lin NT, Chu CH, Huang KC, Liao KW, et al. Different effects of probiotic species/strains on infections in preschool children: a double-blind, randomized, controlled study. Vaccine 2009;27(7):1073-9. - PubMed
Little 2017 {published data only}
    1. Little P, Stuart B, Wingrove Z, Mullee M, Thomas T, Johnson S, et al. Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial. Canadian Medical Association Journal 2017;189(50):E1543-50. [DOI: 10.1503/cmaj.170599] - DOI - PMC - PubMed
Luoto 2013 {published data only}
    1. Luoto R, Ruuskanen O, Waris M, Kalliomäki M, Salminen S, Isolauri E. Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. Journal of Allergy and Clinical Immunology 2014;133(2):405-13. - PMC - PubMed
Mai 2021 {published data only}
    1. Mai TT, Thi Thu P, Thi Hang H, Trang TT, Yui S, Shigehisa A, et al. Efficacy of probiotics on digestive disorders and acute respiratory infections: a controlled clinical trial in young Vietnamese children. European Journal of Clinical Nutrition 2021;75(3):513-20. [DOI: 10.1038/s41430-020-00754-9] - DOI - PMC - PubMed
Makino 2010b {published data only (unpublished sought but not used)}
    1. Makino S, Ikegami S, Kume A, Horiuchi H, Sasaki H, Orii N. Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1. British Journal of Nutrition 2010;104(7):998-1006. - PubMed
Maldonado 2012 {published data only}
    1. Maldonado J, Cañabate F, Sempere L, Vela F, Sánchez AR, Narbona E, et al. Human milk probiotic Lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. Journal of Pediatric Gastroenterology and Nutrition 2012;54(1):55-61. - PubMed
Maldonado‐Lobón 2015 {published data only}
    1. Maldonado-Lobón JA, Gil-Campos M, Maldonado J, López-Huertas E, Flores-Rojas K, Valero AD, et al. Long-term safety of early consumption of Lactobacillus fermentum CECT5716: a 3-year follow-up of a randomized controlled trial. Pharmacological Research 2015;95-6:12-9. [DOI: 10.1016/j.phrs.2015.01.006] - DOI - PubMed
Manti 2020 {published data only}
    1. Manti S, Parisi GF, Papale M, Licari A, Salpietro C, Miraglia Del Giudice M, et al. Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray for treatment of upper respiratory tract infections in children: a pilot study on short-term efficacy. Italian Journal of Pediatrics 2020;46(1):42. [DOI: 10.1186/s13052-020-0798-4] - DOI - PMC - PubMed
Maya‐Barrios 2021 {published data only}
    1. Maya-Barrios A, Lira-Hernandez K, Jiménez-Escobar I, Hernández L, Ortiz-Hernandez A, Jiménez-Gutiérrez C, et al. Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 as adjuvants to improve evolution of pharyngitis/tonsillitis in children: randomised controlled trial. Beneficial Microbes 2021;12(2):137-45. [DOI: 10.3920/BM2020.0171] - DOI - PubMed
Meng 2016 {published data only}
    1. Meng H, Lee Y, Ba Z, Peng J, Lin J, Boyer AS, et al. Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. Molecular Nutrition & Food Research 2016;60(5):1161-71. [DOI: 10.1002/mnfr.201500665] - DOI - PubMed
Michael 2020 {published data only}
    1. Michael DR, Jack AA, Masetti G, Davies TS, Loxley KE, Kerry-Smith J, et al. A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being. Scientific Reports 2020;10(1):4183. [DOI: 10.1038/s41598-020-60991-7] - DOI - PMC - PubMed
Moyad 2010 {published data only}
    1. Moyad MA, Robinson LE, Zawada ET, Kittelsrud J, Chen DG, Reeves SG. Immunogenic yeast-based fermentate for cold/flu-like symptoms in nonvaccinated individuals. Journal of Alternative & Complementary Medicine 2010;16(2):213-8. - PMC - PubMed
Mullish 2021 {published data only}
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Murata 2018 {published data only}
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Nocerino 2017 {published data only}
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Pitkaranta 2003 {published data only (unpublished sought but not used)}
    1. Pitkaranta A, Hatakka K, Blomgren K, Pohjavuori S, Korpela R. Probiotics in prevention of acute otitis media in otitis prone children. In: 8th International Symposium on Recent Advances in Otitis Media. 2003. [ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=cctr&NEWS=...
Pregliasco 2008 {published data only}
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Ringel‐Kulka 2015 {published data only}
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Sanz 2006 {published data only}
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Stojković 2016 {published data only}
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Tajima 1995 {published data only}
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Turchet 2003 {published data only}
    1. Turchet P, Laurenzano M, Auboiron S, Antoine JM. Effect of fermented milk containing the probiotic Lactobacillus casei DN-114001 on winter infections in free-living elderly subjects: a randomised, controlled pilot study. Journal of Nutrition, Health and Aging 2003;7(2):75-7. - PubMed
Turner 2017 {published data only}
    1. Turner RB, Woodfolk JA, Borish L, Steinke JW, Patrie JT, Muehling LM, et al. Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection - a randomised controlled trial. Beneficial Microbes 2017;8(2):207-15. [DOI: 10.3920/BM2016.0160] - DOI - PMC - PubMed
West 2011 {published data only}
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West 2014 {published data only}
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Zhang 2018 {published data only}
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References to studies awaiting assessment

Kaplan 1968 {published data only}
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References to ongoing studies

NCT01782118 {published data only}
    1. NCT01782118. LGG for prevention of infectious complications during PPI treatment in children [Effectiveness of Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children with gastroesophageal reflux disease treated with proton pump inhibitors: randomized double-blind placebo, controlled trial]. clinicaltrials.gov/show/NCT01782118 (first received 1 February 2013).

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