doi: 10.56294/shp2024145

ReviEW

Fecal microbiota transplantation as an effective therapeutic alternative

El trasplante de microbiota fecal como alternativa terapéutica eficaz

Juliana Stupnik¹ *, Gerardo Laube¹ *

¹Universidad Abierta Interamericana, Facultad de Medicina y Ciencias de la Salud, Carrera de Medicina. Buenos Aires, Argentina.

Cite as: Stupnik J, Laube G. Fecal microbiota transplantation as an effective therapeutic alternative. South Health and Policy. 2024; 3:145. https://doi.org/10.56294/shp2024145

Submitted: 09-08-2023                  Revised: 19-10-2023                   Accepted: 07-04-2024                 Published: 08-04-2024

Editor: Dr. Telmo Raúl Aveiro-Róbalo

Corresponding author: Juliana Stupnik *

ABSTRACT

Antibiotic-associated diarrhoea was a common complication of antimicrobial treatment, mainly caused by an imbalance in the gut microbiota. Clostridioides difficile was identified as the most frequent causative agent, capable of triggering pseudomembranous colitis, especially in vulnerable patients. Given the high recurrence rates of conventional treatments, faecal microbiota transplantation was evaluated as an effective therapeutic alternative. This procedure involved transferring faecal material from a healthy donor to an affected recipient, achieving remarkable restoration of intestinal balance, reduced mortality, and significant clinical improvement. In addition to its efficacy, a favourable safety profile and reduced healthcare costs were documented, consolidating it as a key tool in the treatment of recurrent C. difficile infections.

Keywords: Clostridioides Difficile; Dysbiosis; Pseudomembranous Colitis; Microbiota Transplantation; Therapeutic Efficacy.

RESUMEN

La diarrea asociada a antibióticos se presentó como una complicación común del tratamiento antimicrobiano, causada principalmente por un desequilibrio en la microbiota intestinal. Clostridioides difficile se identificó como el agente responsable más frecuente, capaz de desencadenar colitis pseudomembranosa, especialmente en pacientes vulnerables. Frente a las altas tasas de recurrencia de los tratamientos convencionales, se evaluó el trasplante de microbiota fecal como una alternativa terapéutica eficaz. Este procedimiento consistió en transferir material fecal de un donante sano a un receptor afectado, logrando una notable restauración del equilibrio intestinal, reducción de la mortalidad y mejoría clínica significativa. Además de su eficacia, se documentó un perfil de seguridad favorable y una reducción en los costos sanitarios, consolidándolo como una herramienta clave en el tratamiento de infecciones recurrentes por C. difficile.

Palabras clave: Clostridioides Difficile; Disbiosis; Colitis Pseudomembranosa; Trasplante de Microbiota; Eficacia Terapéutica.

INTRODUCTION

Antibiotic-associated diarrhea (AAD) is a common complication in patients receiving antimicrobial treatment, mainly due to an imbalance in the gut microbiota. Among the most relevant causative agents, Clostridioides difficile stands out for its ability to cause pseudomembranous colitis, a potentially serious condition. Given the limitations of conventional antimicrobial treatments, such as high recurrence rates, there has been growing interest in more effective and sustainable therapeutic alternatives. In this context, fecal microbiota transplantation (FMT) is emerging as a promising option for its clinical efficacy, safety, and cost-effectiveness profile.

DEVELOPMENT

Antibiotic-associated diarrhea (AAD) is a common complication of antimicrobial treatment, mainly due to intestinal dysbiosis that allows the proliferation of pathogens such as Clostridioides difficile (CD).⁽¹⁾ This bacterium is recognized as the leading cause of pseudomembranous colitis, a severe inflammatory bowel condition, especially in hospitalized or immunocompromised patients.⁽²⁾

Conventional treatments for Clostridioides difficile infection include antimicrobials such as metronidazole, vancomycin, and fidaxomicin. However, multiple studies have reported high recurrence rates, which has led to growing interest in alternative therapeutic strategies.⁽³⁾ One of the most promising emerging approaches is fecal microbiota transplantation (FMT), which involves transferring fecal material from a healthy donor to a recipient with dysbiosis to restore intestinal microbial balance. The efficacy of FMT has been widely documented. Tixier and Verheyen⁽⁴⁾ demonstrated that this therapy can significantly reduce mortality in patients with severe C. difficile colitis, while systematic studies such as those by Minkoff and Aslam⁽⁵⁾ report a relative risk of disease resolution close to 1,92, higher than that of traditional treatments. Similarly, Song and Kim⁽²⁾ observed cure rates close to 90 % in patients with recurrent infections, thus highlighting the clinical superiority of FMT in refractory settings.

In addition to its clinical efficacy, FMT has shown a favorable safety profile. Although adverse events such as abdominal discomfort or mild diarrhea may occur, serious complications are lower than those of conventional treatments.^(6,7) Martínez et al.⁽⁸⁾ also provide clinical evidence through documented cases where patients with refractory colitis showed significant improvement after receiving FMT, as evidenced by clinical scales such as the Bristol scale.

From an economic standpoint, the analysis by Health Quality Ontario⁽⁶⁾ highlights that FMT represents a cost-effective option by reducing disease recurrence, hospital stays, and the need for additional treatments. Other studies, such as those by Cheng and Fischer⁽⁹⁾, have reaffirmed this, highlighting the role of FMT even in the surgical management of refractory infections.

Finally, it should be noted that the current understanding of the role of the microbiota in intestinal and systemic health has been key to advancing therapies such as FMT. Research such as that by Xu et al.⁽¹⁰⁾ in experimental models has shown that FMT eliminates C. difficile and promotes functional restoration of the intestinal microbiota, consolidating its long-term therapeutic value.

FMT represents a paradigm shift in treating Clostridioides difficile colitis, going beyond the symptomatic approach and targeting the underlying cause: microbial imbalance. Its scientific backing, proven efficacy, and benefits in terms of safety and cost-effectiveness position it as an essential tool in the current clinical management of this disease.

CONCLUSIONS

Fecal microbiota transplantation is establishing itself as an innovative and effective therapeutic intervention for recurrent Clostridioides difficile infections, often surpassing the results obtained with traditional antimicrobial treatments. Its ability to restore intestinal microbial balance, low profile of adverse effects, and positive impact on healthcare costs position it as a key tool in the modern management of C. difficile colitis. As knowledge about the role of the microbiota in human health deepens, FMT is likely to take on an even more important role in clinical practice.

BIBLIOGRAPHICAL REFERENCES

1. Dinleyici M, Vandenplas Y. Clostridium difficile Colitis Prevention and Treatment. Adv Exp Med Biol. 2019;1125:139–46. doi: 10.1007/5584_2018_322. PMID: 30689174.

2. Song JH, Kim YS. Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut Liver. 2019 Jan 15;13(1):16–24. doi: 10.5009/gnl18071. PMID: 30400734; PMCID: PMC6346998.

3. Wilcox MH, McGovern BH, Hecht GA. The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Current Understanding and Gap Analysis. Open Forum Infect Dis. 2020 Apr 11;7(5):ofaa114. doi: 10.1093/ofid/ofaa114. PMID: 32405509; PMCID: PMC7184446.

4. Tixier EN, Verheyen E, Ungaro RC, Grinspan AM. Faecal microbiota transplant decreases mortality in severe and fulminant Clostridioides difficile infection in critically ill patients. Aliment Pharmacol Ther. 2019 Nov;50(10):1094–9. doi: 10.1111/apt.15526. Epub 2019 Oct 14. PMID: 31612528; PMCID: PMC6817391.

5. Minkoff NZ, Aslam S, Medina M, Tanner-Smith EE, Zackular JP, Acra S, et al. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). Cochrane Database Syst Rev. 2023 Apr 25;4(4):CD013871. doi: 10.1002/14651858.CD013871.pub2. PMID: 37096495; PMCID: PMC10125800.

6. Health Quality Ontario. Fecal Microbiota Therapy for Clostridium difficile Infection: A Health Technology Assessment. Ont Health Technol Assess Ser. 2016 Jul 1;16(17):1–69. PMID: 27516814; PMCID: PMC4973962.

7. Gupta K, Tappiti M, Nazir AM, Koganti B, Memon MS, Aslam Zahid MB, et al. Fecal Microbiota Transplant in Recurrent Clostridium difficile Infections: A Systematic Review. Cureus. 2022 May 5;14(5):e24754. doi: 10.7759/cureus.24754. PMID: 35693372; PMCID: PMC9174020.

8. Martínez JV, Raush A, Efrón ED, Zubiaurre I, Pinoni MV, Giorgio PL, et al. Colitis refractaria por Clostridium difficile tratada con trasplante de microbiota fecal [Refractory colitis by Clostridium difficile treated with fecal microbiota transplant]. Medicina (B Aires). 2019;79(4):291–4. Spanish. PMID: 31487251.

9. Cheng YW, Fischer M. Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection. Clin Colon Rectal Surg. 2020 Mar;33(2):92–7. doi: 10.1055/s-0040-1701233. Epub 2020 Feb 25. PMID: 32104162; PMCID: PMC7042019.

10. Xu Q, Zhang S, Quan J, Wu Z, Gu S, Chen Y, et al. The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model. Appl Microbiol Biotechnol. 2022 Oct;106(19-20):6689–700. doi: 10.1007/s00253-022-12154-z. Epub 2022 Sep 10. PMID: 36085529.

FUNDING

None.

CONFLICT OF INTEREST

None.

AUTHOR CONTRIBUTION

Conceptualization: Juliana Stupnik, Gerardo Laube.

Data curation: Juliana Stupnik, Gerardo Laube.

Formal analysis: Juliana Stupnik, Gerardo Laube.

Research: Juliana Stupnik, Gerardo Laube.

Methodology: Juliana Stupnik, Gerardo Laube.

Project management: Juliana Stupnik, Gerardo Laube.

Resources: Juliana Stupnik, Gerardo Laube.

Software: Juliana Stupnik, Gerardo Laube.

Supervision: Juliana Stupnik, Gerardo Laube.

Validation: Juliana Stupnik, Gerardo Laube.

Visualization: Juliana Stupnik, Gerardo Laube.

Writing – original draft: Juliana Stupnik, Gerardo Laube.

Writing – review and editing: Juliana Stupnik, Gerardo Laube.