C. difficile Infection (CDI)
Fecal microbiota transplantation (FMT), based on strong scientific evidence, has been recognized as an appropriate treatment for recurrent Clostridioides difficile infections by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the American College of Gastroenterology (ACG, view link). In Poland, in 2020, the relevant guidelines of the Polish Society of Epidemiology and Infectious Diseases were published, where FMT should be considered as a treatment option in the second episode of CDI, so first recurrence (view link). So far, more than 100 clinical trials and case reports on FMT in CDI have been carried out, and the most thoroughly conducted studies have proven its high effectiveness – about 90%. In the most severe cases, double transplantation is required, ensuring even greater therapy effectiveness. By comparison, vancomycin and other antibiotics are effective at 20-30-50%.
Due to frequent recurrence, scientists are investigating the use of monoclonal antibodies against C. difficile toxins. Actoxumab and bezlotoxumab are both toxin-binding antibodies to A and B, respectively. In addition, bezlotoxumab has been approved by the Food and Drug Administration (FDA), and preliminary clinical studies confirm its action in recurrence prevention, especially when combined with actoxumab. Recently, we have seen the breakthrough discovery of the oral microbiome-derived drug SER-109, which is not classic FMT method. Instead, it consists of purified spores of Firmicutes, and a completed phase III study has confirmed its effectiveness in reducing the risk of recurrence of C. difficile infection. At the same time, researchers are focusing on developing Live Biotherapeutic Products (LBPs) and establishing a new field – microbial therapy.
Currently, the Research and Development Department of the Human Biome Institute created the MicroDrug (Drug Discovery) platform, which is under way to create New-Generation Biotherapeutics, a microbiota based drugs active also against C. difficile.
Role of Microbiota
A healthy, diverse microbiome prevents pathogens from colonizing and developing infections and regulates the immune system’s response. Colonization resistance by penetrating pathogens results from several mechanisms of action of commensal bacteria. The production of antimicrobial peptides and other organic compounds may disrupt the structures of the unwanted microbes’ cell walls. In addition, pathogens must compete with present microbes for food, space, and other resources. When the intestine is in eubiosis, unwanted bacteria do not find the right conditions to survive. An additional role is played by metabolites of intestinal bacteria, especially short-chain fatty acids (SCFA), which are formed during the fermentation of dietary fiber and support the production of the aforementioned antimicrobial peptides. SCFA contributes to the proper production of mucin, which is responsible for maintaining the integrity of the intestinal barrier, preventing the development of inflammation and translocation of pathogens. During C. difficile infection, a decreased amount of mucin is observed, increasing the inflammation in the intestine. Some strains of bacteria, including Bifidobacterium longum supports mucin’s growth, and valeric acid, classified as a short-chain fatty acid, prevents the colonization of Clostridioides difficile. Following FMT, restoration of the appropriate bile acid environment has been observed, removing unwanted acids (e.g., taurocholic acid) that may aid pathogen multiplication. In contrast, secondary bile acids prevent colonization.
FMT from a healthy donor restores a suitable environment in the gut that inhibits the growth and development of C. difficile.
For more information on treating FMT in C. difficile infection, see: view link
To read Guidelines open the following links:
Polish: view link
American: view link
European: view link
Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, Sims M, Kraft CS, Cohen SH, Berenson CS, Korman LY, Ford CB, Litcofsky KD, Lombardo MJ, Wortman JR, Wu H, Auniņš JG, McChalicher CWJ, Winkler JA, McGovern BH, Trucksis M, Henn MR, von Moltke L. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med. 2022 Jan 20;386(3):220-229. doi: 10.1056/NEJMoa2106516. PMID: 35045228.
Rohma Ghani, Benjamin H. Mullish, Lauren A. Roberts, Frances J. Davies & Julian R. Marchesi (2022) The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases, Gut Microbes, 14:1, DOI: 10.1080/19490976.2022.2038856
Wortelboer K, Nieuwdorp M, Herrema H. Fecal microbiota transplantation beyond Clostridioides difficile infections. EBioMedicine. 2019 Jun;44:716-729. doi: 10.1016/j.ebiom.2019.05.066. Epub 2019 Jun 11. PMID: 31201141; PMCID: PMC6606746.