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‘Dark matter’ beyond the bacteria in faecal microbiota transplantation

Nature Reviews Gastroenterology & Hepatology volume 19, page 624 (2022)Cite this article

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Faecal microbiota transplantation (FMT) is increasingly being used in the treatment of various diseases and has demonstrated variable efficacies, with the highest efficacy shown in Clostridioides difficile infection (CDI). For many years, the mechanism of FMT was unclear, and the therapeutic efficacy of FMT was primarily ascribed to the faecal bacteria. However, a groundbreaking study published in 2017 by Ott and colleagues found that sterile faecal filtrate with bacteria removed was still highly efficacious in treating patients with CDI (n = 5). This study demonstrated for the first time that faecal ‘dark matters’ beyond the bacteria were effective in treating disease and ushered in a new era of FMT.

The initial purpose of this proof-of-concept study involving faecal filtrate transplantation was to decrease uncontrollable risks for infectious and metabolic or malignant diseases in patients with CDI, caused by potentially undefined living bacteria in faecal transplants. Strikingly, the authors found that sterile faecal filtrate was sufficient to cure CDI. This finding indicates that faecal components beyond the bacteria might exert crucial roles in FMT. Bacteriophages are substantially smaller in size than bacteria; therefore, they were retained in such sterile faecal filtrate preparations and were posited to have a role in FMT efficacy. On the basis of this logic, the researchers subsequently performed a faecal virome analysis in one of the patients and observed that the gut bacteriophage community (the predominant component of the gut virome) of the patient was restored to a profile resembling that of the faecal donor, along with a restored bacteriome profile. These data suggest that faecal bacteriophages might be a critically functional component in FMT.

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References

Original article

  • Ott, S. J. et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology 152, 799–811 (2017)

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Related article

  • Zuo, T. et al. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut 67, 634–643 (2018)

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Guangdong Institute of Gastroenterology, The sixth affiliated hospital, Sun Yat-sen University, Guangzhou, China

    Tao Zuo

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  1. Tao Zuo
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Correspondence to Tao Zuo.

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The author declares no competing interests.

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Zuo, T. ‘Dark matter’ beyond the bacteria in faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol 19, 624 (2022). https://doi.org/10.1038/s41575-022-00651-5

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