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Annual Review of Medicine

Volume 76, 2025

Probiotics in Health Care: A Critical Appraisal

  • Eamonn M.M. Quigley1 and Fergus Shanahan2
  • 1Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA 2Department of Medicine and Alimentary Pharmabiotic Centre, Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland; email: [email protected]
  • Vol. 76:129-141 (Volume publication date January 2025)
  • First published as a Review in Advance on November 11, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Consumption of probiotic products continues to increase, perhaps driven by an interest in gut health. However, the field is filled with controversy, inconsistencies, misuse of terminology, and poor communication. While the probiotic concept is biologically plausible and in some cases mechanistically well established, extrapolation of preclinical results to humans has seldom been proven in well-conducted clinical trials. With noteworthy exceptions, clinical guidance has often been derived not from large, adequately powered clinical trials but rather from comparisons of disparate, small studies with insufficient power to identify the optimal strain. The separation of probiotics from live biotherapeutic products has brought some clarity from a regulatory perspective, but in both cases, consumers should expect scientific rigor and strong supporting evidence for health claims.

Keyword(s): antibiotic-associated diarrhea, clinical trials, Clostridioides difficile–associated disease, microbiome, necrotizing enterocolitis, probiotics
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2025-01-27
2025-06-16
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Literature Cited

  1. 1.
    Transpar. Mark. Res. 2024.. Global probiotics outlook 2031. Fact Sheet, Transpar. Mark. Res., Wilmington, DE:. https://www.transparencymarketresearch.com/probiotics-market.html
    [Google Scholar]
  2. 2.
    Shanahan F, Dinan TG, Ross P, Hill C. 2021.. Probiotics in transition. . Clin. Gastroenterol. Hepatol. 10::1220–24
     [Google Scholar]
  3. 3.
    Quigley EMM. 2019.. Prebiotics and probiotics in digestive health. . Clin. Gastroenterol. Hepatol. 17::333–44
     [Google Scholar]
  4. 4.
    Orwell G. 1946.. Politics of the English language. . Horizon 13::252–65. https://www.orwellfoundation.com/the-orwell-foundation/orwell/essays-and-other-works/politics-and-the-english-language
    [Google Scholar]
  5. 5.
    Van Baarlen P, Troost F, van der Meer C, et al. 2011.. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. . PNAS 108:(Suppl. 1):4562–69
     [Google Scholar]
  6. 6.
    WHO (World Health Organ.), FAO (Food Agric. Organ.). 2006.. Probiotics in food: health and nutritional properties and guidelines for evaluation. FAO Food Nutr. Pap. 85, FAO, Rome. https://openknowledge.fao.org/server/api/core/bitstreams/382476b3-4d54-4175-803f-2f26f3526256/content
    [Google Scholar]
  7. 7.
    Hill C, Guarner F, Reid G, et al. 2014.. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. . Nat. Rev. Gastroenterol. Hepatol. 11::506–14
     [Google Scholar]
  8. 8.
    Dronkers TMG, Ouwehand AC, Rijkers GT. 2020.. Global analysis of clinical trials with probiotics. . Heliyon 6::e04467
     [Google Scholar]
  9. 9.
    Cordaillat-Simmons M, Rouanet A, Pot B. 2020.. Live biotherapeutic products: the importance of a defined regulatory framework. . Exp. Mol. Med. 52::1397–406
     [Google Scholar]
  10. 10.
    Maldonado-Gómez MX, Martinez I, Bottacini F, et al. 2016.. Stable engraftment of Bifidobacteriumlongum AH1206 in the human gut depends on individualized features of the resident microbiome. . Cell Host Microbe 20::515–26
     [Google Scholar]
  11. 11.
    Salminen S, Collado MC, Endo A, et al. 2021.. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. . Nat. Rev. Gastroenterol. Hepatol. 18::649–67
     [Google Scholar]
  12. 12.
    Aguilar-Toalá JE, Arioli S, Behare P, et al. 2021.. Postbiotics—when simplification fails to clarify. . Nat. Rev. Gastroenterol. Hepatol. 18::825–26
     [Google Scholar]
  13. 13.
    Wang Y, Huang Y, Chase RC, et al. 2023.. Global burden of digestive diseases: a systematic analysis of the Global Burden of Diseases Study, 1990 to 2019. . Gastroenterology 165::773–83
     [Google Scholar]
  14. 14.
    Szajewska H, Mrukowicz JZ. 2001.. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. . J. Pediatr. Gastroenterol. Nutr. 33::S17–25
     [Google Scholar]
  15. 15.
    Huang JS, Bousvaros A, Lee JW, et al. 2002.. Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. . Dig. Dis. Sci. 47::2625–34
     [Google Scholar]
  16. 16.
    Allen SJ, Martinez EG, Gregorio GV, Dans LF. 2010.. Probiotics for treating acute infectious diarrhoea. . Cochrane Database Syst. Rev. 11::CD003048
     [Google Scholar]
  17. 17.
    Preidis GA, Weizman AV, Kashyap PC, Morgan RL. 2020.. AGA technical review on the role of probiotics in the management of gastrointestinal disorders. . Gastroenterology 159::708–38
     [Google Scholar]
  18. 18.
    Schnadower D, Tarr PI, Casper TC, et al. 2018.. Lactobacillusrhamnosus GG versus placebo for acute gastroenteritis in children. . N. Engl. J. Med. 379::2002–14
     [Google Scholar]
  19. 19.
    Freedman SB, Williamson-Urquhart S, Farion KJ, et al. 2018.. Multicenter trial of a combination probiotic for children with gastroenteritis. . N. Engl. J. Med. 379::2015–26
     [Google Scholar]
  20. 20.
    Weizman Z. 2019.. Lactobacillus for gastroenteritis in children. . N. Engl. J. Med. 380::e36
     [Google Scholar]
  21. 21.
    Berni Canani R. 2019.. Lactobacillus for gastroenteritis in children. . N. Engl. J. Med. 380::e36
     [Google Scholar]
  22. 22.
    Motamedi H, Fathollahi M, Abiri R, et al. 2021.. A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients. . PLOS ONE 16::e0260667
     [Google Scholar]
  23. 23.
    Di Bella S, Sanson G, Monticelli J, et al. 2024.. Clostridioidesdifficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options. . Clin. Microbiol. Rev. 37::e0013523
     [Google Scholar]
  24. 24.
    Freeman J, Bauer MP, Baines SD, et al. 2010.. The changing epidemiology of Clostridiumdifficile infections. . Clin. Microbiol. Rev. 23::529–49
     [Google Scholar]
  25. 25.
    Karas JA, Enoch DA, Aliyu SH. 2010.. A review of mortality due to Clostridiumdifficile infection. . J. Infect. 61::20
     [Google Scholar]
  26. 26.
    Guh AY, Mu Y, Winston LG, et al. 2020.. Emerging Infections Program Clostridioidesdifficile Infection Working Group: trends in U.S. burden of Clostridioidesdifficile infection and outcomes. . N. Engl. J. Med. 382::1320–30
     [Google Scholar]
  27. 27.
    McFarland LV. 2006.. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridiumdifficile disease. . Am. J. Gastroenterol. 101::812–22
     [Google Scholar]
  28. 28.
    Johnston BC, Goldenberg JZ, Vandvik PO, et al. 2011.. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. . Cochrane Database Syst. Rev. 11::CD004827
     [Google Scholar]
  29. 29.
    Goldenberg JZ, Ma SSY, Saxton JD, et al. 2013.. Probiotics for the prevention of Clostridiumdifficile–associated diarrhea in adults and children. . Cochrane Database Syst. Rev. 5::CD006095
     [Google Scholar]
  30. 30.
    Videlock EJ, Cremonini F. 2012.. Meta-analysis: probiotics in antibiotic-associated diarrhoea. Aliment. . Pharmacol. Ther. 35::1355–69
     [Google Scholar]
  31. 31.
    Gao XW, Mubasher M, Fang CY, et al. 2010.. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacilluscasei LBC80R for antibiotic-associated diarrhea and Clostridiumdifficile–associated diarrhea prophylaxis in adult patients. . Am. J. Gastroenterol. 105::1636–41
     [Google Scholar]
  32. 32.
    Johnson S, Maziade PJ, McFarland LV, et al. 2012.. Is primary prevention of Clostridiumdifficile infection possible with specific probiotics?. Int. J. Infect. Dis. 16::e786–92
     [Google Scholar]
  33. 33.
    Ma Y, Yang JY, Peng X, et al. 2020.. Which probiotic has the best effect on preventing Clostridiumdifficile–associated diarrhea? A systematic review and network meta-analysis. . J. Dig. Dis. 21::69–80
     [Google Scholar]
  34. 34.
    Allen SJ, Wareham K, Wang D, et al. 2013.. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridiumdifficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. . Lancet 382::1249–57
     [Google Scholar]
  35. 35.
    Guo Q, Goldenberg JZ, Humphrey C, et al. 2019.. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. . Cochrane Database Syst. Rev. 4::CD004827
     [Google Scholar]
  36. 36.
    Goldenberg JZ, Yap C, Lytvyn L, et al. 2017.. Probiotics for the prevention of Clostridiumdifficile–associated diarrhea in adults and children. . Cochrane Database Syst. Rev. 12::CD006095
     [Google Scholar]
  37. 37.
    Kelly CR, Fischer M, Allegretti JR, et al. 2021.. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioidesdifficile infections. . Am. J. Gastroenterol. 116::1124–47
     [Google Scholar]
  38. 38.
    Jones IH, Hall NJ. 2020.. Contemporary outcomes for infants with necrotizing enterocolitis—a systematic review. . J. Pediatr. 220::86–92
     [Google Scholar]
  39. 39.
    Stanikova A, Jouza M, Bohosova J, et al. 2023.. Role of the microbiome in pathophysiology of necrotising enterocolitis in preterm neonates. . BMJ Paediatr. Open 7::e002172
     [Google Scholar]
  40. 40.
    Morgan RL, Preidis GA, Kashyap PC, et al. 2020.. Probiotics reduce mortality and morbidity in preterm, low-birth-weight infants: a systematic review and network meta-analysis of randomized trials. . Gastroenterology 159::467–80
     [Google Scholar]
  41. 41.
    Szajewska H, Berni Canani R, Domellöf M, et al. 2023.. Probiotics for the management of pediatric gastrointestinal disorders: position paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. . J. Pediatr. Gastroenterol. Nutr. 76::232–47
     [Google Scholar]
  42. 42.
    Fallon EM, Nehra D, Potemkin AK, et al. 2012.. A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis. . J. Parenter. Enter. Nutr. 36::506–23
     [Google Scholar]
  43. 43.
    Sharif S, Meader N, Oddie SJ, et al. 2020.. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. . Cochrane Database Syst. Rev. 10::CD005496
     [Google Scholar]
  44. 44.
    Agha L, Staiger D, Brown C, et al. 2023.. Association of hospital adoption of probiotics with outcomes among neonates with very low birth weight. . JAMA Health Forum 4::e230960
     [Google Scholar]
  45. 45.
    Singh P, Lembo A. 2021.. Emerging role of the gut microbiome in irritable bowel syndrome. . Gastroenterol. Clin. N. Am. 50::523–45
     [Google Scholar]
  46. 46.
    McFarland LV, Dublin S. 2008.. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. . World J. Gastroenterol. 14::2650–61
     [Google Scholar]
  47. 47.
    Hoveyda N, Heneghan C, Mahtani KR, et al. 2009.. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. . BMC Gastroenterol. 9::15
     [Google Scholar]
  48. 48.
    Moayyedi P, Ford AC, Talley NJ, et al. 2010.. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. . Gut 59::325–32
     [Google Scholar]
  49. 49.
    Ford AC, Quigley EMM, Lacy BE, et al. 2014.. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. . Am. J. Gastroenterol. 109::1547–61
     [Google Scholar]
  50. 50.
    Ford AC, Harris LA, Lacy BE, et al. 2018.. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. . Aliment. Pharmacol. Ther. 48::1044–60
     [Google Scholar]
  51. 51.
    Goodoory VC, Khasawneh M, Black CJ, et al. 2023.. Efficacy of probiotics in irritable bowel syndrome: systematic review and meta-analysis. . Gastroenterology 165::1206–18
     [Google Scholar]
  52. 52.
    Goethel A, Croitoru K, Philpott DJ. 2018.. The interplay between microbes and the immune response in inflammatory bowel disease. . J. Physiol. 596::3869–82
     [Google Scholar]
  53. 53.
    Zhang L, Agrawal M, Ng SC, Jess T. 2024.. Early-life exposures and the microbiome: implications for IBD prevention. . Gut 73::541–49
     [Google Scholar]
  54. 54.
    Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall FJ. 2006.. Probiotics for maintenance of remission in Crohn's disease. . Cochrane Database Syst. Rev. 4::CD004826
     [Google Scholar]
  55. 55.
    Mallon P, McKay D, Kirk SJ, Gardiner K. 2007.. Probiotics for induction of remission in ulcerative colitis. . Cochrane Database Syst. Rev. 4::CD005573
     [Google Scholar]
  56. 56.
    Rahimi R, Nikfar S, Rahimi F, et al. 2008.. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease. . Dig. Dis. Sci. 53::2524–31
     [Google Scholar]
  57. 57.
    Naidoo K, Gordon M, Fagbemi AO, et al. 2011.. Probiotics for maintenance of remission in ulcerative colitis. . Cochrane Database Syst. Rev. 12::CD007443
     [Google Scholar]
  58. 58.
    Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. 2017.. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. . Aliment. Pharmacol. Ther. 46::389–400
     [Google Scholar]
  59. 59.
    Jia K, Tong X, Wang R, Song X. 2018.. The clinical effects of probiotics for inflammatory bowel disease: a meta-analysis. . Medicine 97::e13792
     [Google Scholar]
  60. 60.
    Astó E, Méndez I, Audivert S, et al. 2019.. The efficacy of probiotics, prebiotic inulin-type fructans, and synbiotics in human ulcerative colitis: a systematic review and meta-analysis. . Nutrients 11::E293
     [Google Scholar]
  61. 61.
    Limketkai BN, Akobeng AK, Gordon M, Adepoju AA. 2020.. Probiotics for induction of remission in Crohn's disease. . Cochrane Database Syst. Rev. 7::CD006634
     [Google Scholar]
  62. 62.
    Kaur L, Gordon M, Baines PA, et al. 2020.. Probiotics for induction of remission in ulcerative colitis. . Cochrane Database Syst. Rev. 3::CD005573
     [Google Scholar]
  63. 63.
    Iheozor-Ejiofor Z, Kaur L, Gordon M, et al. 2020.. Probiotics for maintenance of remission in ulcerative colitis. . Database Syst. Rev. 3::CD007443
     [Google Scholar]
  64. 64.
    Singh S, Stroud AM, Holubar SD, et al. 2015.. Treatment and prevention of pouchitis after ileal pouch–anal anastomosis for chronic ulcerative colitis. . Cochrane Database Syst. Rev. 11::CD001176
     [Google Scholar]
  65. 65.
    Xiao W, Zhao X, Li C, et al. 2023.. The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch–anal anastomosis: a meta-analysis. . Technol. Health Care 31::401–15
     [Google Scholar]
  66. 66.
    Emile SH, Horesh N, Freund MR, et al. 2023.. A systematic review and meta-analysis of randomized clinical trials on the prevention and treatment of pouchitis after ileoanal pouch anastomosis. . J. Gastrointest. Surg. 27::2650–60
     [Google Scholar]
  67. 67.
    Kristensen N, Bryrup T, Allin KH, et al. 2016.. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. . Genome Med. 8::52
     [Google Scholar]
  68. 68.
    Suez J, Zmora N, Zilberman-Schapira G, et al. 2018.. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. . Cell 174::1406–23.e16
     [Google Scholar]
  69. 69.
    Panigrahi P, Parida S, Nanda NC, et al. 2017.. A randomized synbiotic trial to prevent sepsis among infants in rural India. . Nature 548::407–12
     [Google Scholar]
  70. 70.
    Hao Q, Lu Z, Dong BR, et al. 2011.. Probiotics for preventing acute upper respiratory tract infections. . Cochrane Database Syst. Rev. 9::CD006895
     [Google Scholar]
  71. 71.
    King S, Glanville J, Sanders ME, et al. 2014.. Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis. . Br. J. Nutr. 112::41–54
     [Google Scholar]
  72. 72.
    Hao Q, Dong BR, Wu T. 2015.. Probiotics for preventing acute upper respiratory tract infections. . Cochrane Database Syst. Rev. 2::CD006895
     [Google Scholar]
  73. 73.
    King S, Tancredi D, Lenoir-Wijnkoop I, et al. 2019.. Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis. . Eur. J. Public Health 29::494–99
     [Google Scholar]
  74. 74.
    Chan CKY, Tao J, Chan OS, et al. 2020.. Preventing respiratory tract infections by synbiotic interventions: a systematic review and meta-analysis of randomized controlled trials. . Adv. Nutr. 11::979–88
     [Google Scholar]
  75. 75.
    Rashidi K, Razi B, Darand M, et al. 2021.. Effect of probiotic fermented dairy products on incidence of respiratory tract infections: a systematic review and meta-analysis of randomized clinical trials. . Nutr. J. 20::61
     [Google Scholar]
  76. 76.
    Cuello-Garcia CA, Brożek JL, Fiocchi A, et al. 2015.. Probiotics for the prevention of allergy: a systematic review and meta-analysis of randomized controlled trials. . J. Allergy Clin. Immunol. 136::952–61
     [Google Scholar]
  77. 77.
    Sun S, Chang G, Zhang L. 2022.. The prevention effect of probiotics against eczema in children: an update systematic review and meta-analysis. . J. Dermatol. Treat. 33::1844–54
     [Google Scholar]
  78. 78.
    Poon T, Juana J, Noori D, et al. 2020.. Effects of a fermented dairy drink containing Lacticaseibacillusparacasei subsp. paracasei CNCM I-1518 (Lactobacilluscasei CNCM I-1518) and the standard yogurt cultures on the incidence, duration, and severity of common infectious diseases: a systematic review and meta-analysis of randomized controlled trials. . Nutrients 12::3443
     [Google Scholar]
  79. 79.
    Merenstein D, Pot B, Leyer G, et al. 2023.. Emerging issues in probiotic safety: 2023 perspectives. . Gut Microbes 15::2185034
     [Google Scholar]
  80. 80.
    FDA (Food Drug Adm.). 2023.. FDA raises concerns about probiotic products sold for use in hospitalized preterm infants. Press Release, FDA, Washington, DC:, Oct. 26. https://www.fda.gov/news-events/press-announcements/fda-raises-concerns-about-probiotic-products-sold-use-hospitalized-preterm-infants
    [Google Scholar]
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Probiotics in Health Care: A Critical Appraisal
Annual Review of Medicine 76, 129 (2025); https://doi.org/10.1146/annurev-med-042423-042315
/content/journals/10.1146/annurev-med-042423-042315
/content/journals/10.1146/annurev-med-042423-042315
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