Manipulation of the gut microbiota: probiotics and fecal microbiota transplantation as a treatment option for recurrent Clostridium difficile infection

Wiktoria Feret, Magdalena Nalewajska, Kazimierz Ciechanowski


Diarrhea and other gastrointestinal symptoms are possible side effects of long-term antibiotic therapy. The most common etiology of hospital-acquired diarrhea is Clostridium difficile infection (CDI). It has been demonstrated that probiotic use may be beneficial in the prevention of antibiotic-associated diarrhea. There is also growing evidence that a fecal microbiota transplant may reduce the duration and recurrence of CDI. In this review, we update the current knowledge on both modalities in the prevention of resistant CDI and as useful adjuncts to standard treatment.


fecal microbiota transplantation; clostridium difficile; probiotics; microbiome; microbiota

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Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis 2019;38(7):1211-21.

Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med 2015;372(16):1539-48.

Evans CT, Safdar N. Current trends in the epidemiology and outcomes of Clostridium difficile infection. Clin Infect Dis 2015;60 Suppl 2:S66-71.

Ng SC, Hart AL, Kamm MA, Stagg AJ, Knight SC. Mechanisms of action of probiotics: Recent advances. Inflamm Bowel Dis 2009;15(2):300-10.

Cremonini F, Di Caro S, Santarelli L, Gabrielli M, Candelli M, Nista EC, et al. Probiotics in antibiotic-associated diarrhoea. Dig Liver Dis 2002;34 Suppl 2:S78-80.

Rolfe RD. The role of probiotic cultures in the control of gastrointestinal health. J Nutr 2000;130(2S Suppl):396S-402S.

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

Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev 2017;12(12):CD006095.

Ma Y, Yang JY, Peng X, Xiao KY, Xu Q, Wang C. Which probiotic has the best effect on preventing Clostridium difficile-associated diarrhea? A systematic review and network meta-analysis. J Dig Dis 2020;21(2):69-80.

Thornhill MH, Dayer MJ, Durkin MJ, Lockhart PB, Baddour LM. Risk of adverse reactions to oral antibiotics prescribed by dentists. J Dent Res 2019;98(10):1081-7. doi: 10.1177/0022034519863645.

Aabed K, Shafi Bhat R, Moubayed N, Al-Mutiri M, Al-Marshoud M, Al-Qahtani A, et al. Ameliorative effect of probiotics (Lactobacillus paracaseii and Protexin®) and prebiotics (propolis and bee pollen) on clindamycin and propionic acid-induced oxidative stress and altered gut microbiota in a rodent model of autism. Cell Mol Biol (Noisy-le-grand) 2019;65(1):1-7.

Wei Y, Yang F, Wu Q, Gao J, Liu W, Liu C, et al. Protective effects of bifidobacterial strains against toxigenic Clostridium difficile. Front Microbiol 2018;9:888.

Xu Q, Gu S, Chen Y, Quan J, Lv L, Chen D, et al. Protective effect of Pediococcus pentosaceus LI05 against Clostridium difficile infection in a mouse model. Front Microbiol 2018;9:2396.

Golić N, Veljović K, Popović N, Djokić J, Strahinić I, Mrvaljević I, et al. In vitro and in vivo antagonistic activity of new probiotic culture against Clostridium difficile and Clostridium perfringens. BMC Microbiol 2017;17(1):108.

Evans M, Salewski RP, Christman MC, Girard SA, Tompkins TA. Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial. Br J Nutr 2016;116(1):94-103.

Barker AK, Duster M, Valentine S, Hess T, Archbald-Pannone L, Guerrant R, et al. A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO). J Antimicrob Chemother 2017;72(11):3177-80.

McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW, Moyer KA, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994;271(24):1913-8.

Kabbani TA, Pallav K, Dowd SE, Villafuerte-Galvez J, Vanga RR, Castillo NE, et al. Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers. Gut Microbes 2017;8(1):17-32.

Tariq R, Pardi DS, Bartlett MG, Khanna S. Low cure rates in controlled trials of fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Clin Infect Dis 2019;68(8):1351-8. doi: 10.1093/cid/ciy721.

Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2016;315(2):142-9.

Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, et al. Systematic review: adverse events of fecal microbiota transplantation. PLoS One 2016;11(8):e0161174.

Grigoryan Z, Shen MJ, Twardus SW, Beuttler MM, Chen LA, Bateman- -House A. Fecal microbiota transplantation: uses, questions, and ethics. Med Microecol 2020;6:100027.

Park S, Seo GS. Fecal microbiota transplantation: Where is it leading? Gastroenterol Hepatol 2014;10(5):307-9.

Bibbò S, Settanni CR, Porcari S, Bocchino E, Ianiro G, Cammarota G, et al. Fecal microbiota transplantation: screening and selection to choose the optimal donor. J Clin Med 2020;9(6):1757.

Bafeta A, Yavchitz A, Riveros C, Batista R, Ravaud P. Methods and reporting studies assessing fecal microbiota transplantation: a systematic review. Ann Intern Med 2017;167(1):34-9.

Cohen NA, Livovsky DM, Yaakobovitch S, Ben Yehoyada M, Ben Ami R, Adler A, et al. A Retrospective Comparison of Fecal Microbial Transplantation Methods for Recurrent Clostridium Difficile Infection. Isr Med Assoc J 2016;18(10):594-9.


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