Skip to main content

Advertisement

Log in

Probiotics in health and disease: fooling Mother Nature?

  • Review
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Probiotics are ubiquitous, consumption by the general public is common, and the dogma remains that they are beneficial for general and gut health. However, evolving evidence suggests a potentially “harmful” impact of many commercially available probiotics. There is also significant variability in formulations that leads to a lack of a universally acceptable definition of probiotics. In this perspective, we review the flaws with definition, relevant observational and randomized studies that showed both positive and negative impacts on health and disease, unbiased interpretation of key trials, emerging evidence from microbiome and immuno-oncological studies, and impact on systemic immunity. We propose that caution be exercised prior to endorsements of their illness-directed consumption and rampant general usage. As a deeper understanding of the human microbiome accrues and our ability to manipulate this complex ecosystem improves, the probiotic of tomorrow might be the precision tool that deals with diseases on a broad front. Gut microbiome, akin to fingerprints, is indigenous to an individual and ‘one size fits all’ prescription strategy should be discouraged until a more universally acceptable ‘favorable taxa’ or a ‘personalized probiotic,’ to complement an individual’s native microbiota, gets fashioned.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002–2012. Natl Health Stat Rep. 2015;79:1–16.

    Google Scholar 

  2. Yi SH, Jernigan JA, McDonald LC. Prevalence of probiotic use among inpatients: a descriptive study of 145 U.S. hospitals. Am J Infect Control. 2016;44(5):548–53.

    PubMed  Google Scholar 

  3. Agerbaek M, Gerdes LU, Richelsen B. Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men. Eur J Clin Nutr. 1995;49(5):346–52.

    CAS  PubMed  Google Scholar 

  4. Rajkumar H, Mahmood N, Kumar M, Varikuti SR, Challa HR, Myakala SP. Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators Inflamm. 2014;2014:348959.

    PubMed  PubMed Central  Google Scholar 

  5. Bjerg AT, Sorensen MB, Krych L, et al. The effect of Lactobacillus paracasei subsp. paracasei L. casei W8(R) on blood levels of triacylglycerol is independent of colonisation. Benef Microbes. 2015;6(3):263–9.

    CAS  PubMed  Google Scholar 

  6. Tyagi AM, Yu M, Darby TM, et al. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression. Immunity. 2018;49(6):1116–1131e1117.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2010;126(3):e526–33.

    PubMed  Google Scholar 

  8. Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959–69.

    CAS  PubMed  Google Scholar 

  9. Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2015;12:CD004827.

    Google Scholar 

  10. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101(4):812–22.

    PubMed  Google Scholar 

  11. Hungin AP, Mulligan C, Pot B, et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice—an evidence-based international guide. Aliment Pharmacol Ther. 2013;38(8):864–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Panigrahi P, Parida S, Nanda NC, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017;548(7668):407–12.

    CAS  PubMed  Google Scholar 

  13. Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8(1):4.

    PubMed  PubMed Central  Google Scholar 

  14. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun. 1999;67(1):302–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Lau CS, Ward A, Chamberlain RS. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis. Infect Drug Resist. 2016;9:275–89.

    PubMed  PubMed Central  Google Scholar 

  16. Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR, Probiotics in Preterm Infants Study Collaborative G. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet. 2016;387(10019):649–60.

    PubMed  Google Scholar 

  17. Allen SJ, Wareham K, Wang D, et al. A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE). Health Technol Assess. 2013;17(57):1–140.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Little P, Stuart B, Wingrove Z, et al. Probiotic capsules and xylitol chewing gum to manage symptoms of pharyngitis: a randomized controlled factorial trial. CMAJ. 2017;189(50):E1543–50.

    PubMed  PubMed Central  Google Scholar 

  19. Freedman SB, Williamson-Urquhart S, Farion KJ, et al. Multicenter trial of a combination probiotic for children with gastroenteritis. N Engl J Med. 2018;379(21):2015–26.

    CAS  PubMed  Google Scholar 

  20. Schnadower D, Tarr PI, Casper TC, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med. 2018;379(21):2002–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371(9613):651–9.

    PubMed  Google Scholar 

  22. Suez J, Zmora N, Zilberman-Schapira G, et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174(6):1406–1423e1416.

    CAS  PubMed  Google Scholar 

  23. Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of probiotics. Expert Opin Drug Saf. 2014;13(2):227–39.

    PubMed  Google Scholar 

  24. Zmora N, Zilberman-Schapira G, Suez J, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell. 2018;174(6):1388–1405e1321.

    CAS  PubMed  Google Scholar 

  25. LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med. 1997;337(8):536–42.

    CAS  PubMed  Google Scholar 

  26. Million M, Raoult D. Publication biases in probiotics. Eur J Epidemiol. 2012;27(11):885–6.

    PubMed  Google Scholar 

  27. Piewngam P, Zheng Y, Nguyen TH, et al. Pathogen elimination by probiotic Bacillus via signalling interference. Nature. 2018;562(7728):532–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Sassone-Corsi M, Nuccio SP, Liu H, et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature. 2016;540(7632):280–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Omenetti S, Pizarro TT. The Treg/Th17 axis: a dynamic balance regulated by the gut microbiome. Front Immunol. 2015;6:639.

    PubMed  PubMed Central  Google Scholar 

  30. Browne HP, Forster SC, Anonye BO, et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature. 2016;533(7604):543–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14.

    Google Scholar 

  32. Zhao L. The gut microbiota and obesity: from correlation to causality. Nat Rev Microbiol. 2013;11(9):639–47.

    CAS  PubMed  Google Scholar 

  33. Yacoub R, Jacob A, Wlaschin J, McGregor M, Quigg RJ, Alexander JJ. Lupus: The microbiome angle. Immunobiology. 2018;223(6–7):460–5.

    CAS  PubMed  Google Scholar 

  34. Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014;38:1–12.

    PubMed  Google Scholar 

  35. Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124(10):4204–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Karbach SH, Schonfelder T, Brandao I, et al. Gut microbiota promote angiotensin II-induced arterial hypertension and vascular dysfunction. J Am Heart Assoc. 2016. https://doi.org/10.1161/JAHA.116.003698.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Huda MN, Lewis Z, Kalanetra KM, et al. Stool microbiota and vaccine responses of infants. Pediatrics. 2014;134(2):e362–72.

    PubMed  PubMed Central  Google Scholar 

  38. Atarashi K, Tanoue T, Ando M, et al. Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell. 2015;163(2):367–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Abid MB. Could the menagerie of the gut microbiome really cure cancer? Hope or hype. J Immunother Cancer. 2019;7(1):92.

    PubMed  PubMed Central  Google Scholar 

  40. Tanoue T, Morita S, Plichta DR, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565(7741):600–5.

    CAS  PubMed  Google Scholar 

  41. Gopalakrishnan V, Spencer C, McQuade J, et al. The gut microbiome of metastatic melanoma patients initiating systemic therapy is influenced by host factors including diet, probiotic and antibiotic use. P505. The Annual Meeting of the Society for Immunotherapy of Cancer. November 7–11, 2018. Washington, DC.

  42. “Global Probiotics Market Will Reach USD 65.87 Billion by 2024: Zion Market Research.” “GlobeNewswire”, 21 June 2018, globenewswire.com/news-release/2018/06/21/1527822/0/en/Global-Probiotics-Market-Will-Reach-USD-65-87-Billion-by-2024-Zion-Market-Research.html. Accessed 7 Mar 2019.

  43. “Global Antihypertensive Drugs Market US$ 23.1 Billion by 2023.” Healthcare Market Research and Consulting Services, IHealthcareAnalyst, Inc, 28 Sept. 2018, www.ihealthcareanalyst.com/global-antihypertensive-drugs-market/. Accessed 7 Mar 2019.

  44. Venugopalan V, Shriner KA, Wong-Beringer A. Regulatory oversight and safety of probiotic use. Emerg Infect Dis. 2010;16(11):1661–5.

    PubMed  PubMed Central  Google Scholar 

  45. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;2:CD006895.

    Google Scholar 

  46. Barrett HL, Dekker Nitert M, Conwell LS, Callaway LK. Probiotics for preventing gestational diabetes. Cochrane Database Syst Rev. 2014;2:CD009951.

    Google Scholar 

  47. Shane AL, Mody RK, Crump JA, et al. Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017;65(12):1963–73.

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

MBA conceived of the idea, performed the literature search, wrote the manuscript, and drew the table. CJK co-wrote the manuscript. Both authors performed a critical revision of the manuscript.

Corresponding author

Correspondence to Muhammad Bilal Abid.

Ethics declarations

Conflict of interest

The authors declare no potential conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abid, M.B., Koh, C.J. Probiotics in health and disease: fooling Mother Nature?. Infection 47, 911–917 (2019). https://doi.org/10.1007/s15010-019-01351-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-019-01351-0

Keywords

Navigation