Fecal microbiota transplantation: a review on current formulations in Clostridioides difficile infection and future outlooks

ABSTRACT

Introduction

The role of the gut microbiota in health and the pathogenesis of several diseases has been highlighted in recent years. Even though the precise mechanisms involving the microbiome in these ailments are still unclear, microbiota-modulating therapies have been developed. Fecal microbiota transplantation (FMT) has shown significant results against Clostridioides difficile infection (CDI), and its potential has been investigated for other diseases. Unfortunately, the technical aspects of the treatment make it difficult to implement. Pharmaceutical technology approaches to encapsulate microorganisms could play an important role in providing this treatment and render the treatment modalities easier to handle.

Areas covered

After an overview of CDI, this narrative review aims to discuss the current formulations for FMT and specifically addresses the technical aspects of the treatment. This review also distinguishes itself by focusing on the hurdles and emphasizing the possible improvements using pharmaceutical technologies.

Expert Opinion

FMT is an efficient treatment for recurrent CDI. However, its standardization is overlooked. The approach of industrial and hospital preparations of FMT are different, but both show promise in their respective methodologies. Novel FMT formulations could enable further research on dysbiotic diseases in the future.

PLAIN LANGUAGE SUMMARY

Multiple microorganisms cohabit with us: viruses, Archaea, fungi and, most predominantly, bacteria. They are called the microbiota. In fact, our body has ‘good’ and ‘bad’ bacteria. ‘Good’ bacteria help us stay in good health and fight off ‘bad’ bacteria. Recent research has revealed the relationship between the microbiota and several diseases, such as Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a common hospital-acquired infection. Approximately 130,000 cases are reported every year in Europe. Severe cases appear in 6 per 100 patients and can lead to death. In addition, 13 patients among 20 will experience a recurrent infection and cannot be treated using the standard antibiotic treatment. In this disease, researchers observed an imbalance between the ‘good’ and ‘bad’ bacteria, among other elements. The need for procedures to regulate the microbiota has thus risen. Fecal microbiota transplantation (FMT) is a very efficient and safe treatment for recurrent CDI. One of the most significant challenges of FMT is its formulation, because it is administered via uncomfortable routes. Additionally, implementing FMT is very time consuming. As such, developing novel pharmaceutical technologies for FMT will enable the study of more diseases associated with an imbalance of the microbiota.

This review explains the importance of the microbiota in CDI and how the formulation of FMT has evolved. Additionally, we propose possible ameliorations to FMT using well-established pharmaceutical technologies and how they could play a role in future research on microbiota-related diseases.

KEYWORDS:

• Bacterial formulation
• Clostridioides difficile infection
• dysbiosis
• fecal microbiota transplantation
• live bacteria administration
• microbiota
• pharmaceutical technology

Article highlights

• Fecal microbiota transplantation is a very efficient and safe treatment against recurrent Clostridioides difficile infection

• FMT has evolved from rough formulations to organizational-friendly options

• FMT formulation could be further enhanced using novel pharmaceutical technologies

• Magistral preparation of FMT could help develop personalized medicine, while industrial preparation of FMT could help expand the use of this treatment.

• Pharmaceutical technologies used for live bacterial formulations could be used to enhance the handling and storage of bacterial strains over time while maintaining their viability.

This box summarizes key points contained in the article.

Acknowledgments

Figures were created using Servier Medical Art at smart.servier.com and BioRender at biorender.com.

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the University of Geneva, State/Canton of Geneva.