Success of fecal transplant is conditioned by intestinal mycobiota

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Proliferation of an opportunistic yeast in the intestines could be the cause of fecal transplant failure in the treatment of Clostridium difficile infections. Outcome might be improved by reversing fungal dysbiosis.

 

In ten years, fecal microbiota transplants (FMT) have led to recovery rates between 85 and 90% in the treatment of Clostridium difficile infections. However, rates are significantly lower for chronic inflammatory bowel diseases (CIBD), as they stand between 30 and 50%. A team of Chinese researchers studied the gut mycobiota (fungal counterpart of the gut microbiota that is still relatively poorly studied) to assess its role in the success of FMT.

Fungal dysbiosis observed in patients

Scientists observed that the gut mycobiota of people infected with C. difficile was much more abundant but less diversified and less rich in fungal species than that of healthy individuals. Most of all, it contained high levels of Candida albicans*, an opportunistic yeast, and even more so when patients had previously been treated with antibiotics, whose adverse effect is precisely to promote the growth of C. albicans.

Donors and recipients: mycobiota should be monitored

This abundance of C. albicans was pivotal in the outcome of FMT: the mycobiota of responders (i.e. patients with no relapse of C. difficile infection) was generally richer, more diversified, and with lower levels of C. albicans compared to that of non-responders and showed high levels of Saccharomyces and Aspergillus. Similarly, all patients with high levels of C. albicans before and after the transplant relapsed. The presence of this opportunistic yeast in donors was also associated to a higher FMT failure rate. Finally, the researchers demonstrated that vancomycin, the gold standard treatment for C. difficile infections, increased C. albicans levels in the mycobiota of all transplant recipients. These results were corroborated by a mouse model of C. difficile infection, confirming the negative impact of C. albicans overabundance in transplant donors and/or recipients.

Microbiota, mycobiota and immunity

One theory is that C. albicans could have a direct pro-inflammatory action by modulating the Th17/Treg balance which is key to auto-immunity. Moreover, when antibiotics eradicate commensal bacteria in the gut flora, they remove the bacterial shield that limits Candida sp. growth through the immune system**. If these results were confirmed, screening for C. albicans in donors and eradicating it before the transplant, could improve prognosis.

 

*It can trigger mucocutaneous (oral, genital, esophageal) or systemic candidiasis.

**Through the activation of antimicrobial peptide LL-37 and transcription factor HIF-1α that acts on innate cellular immune effectors.

 

Sources:

Zuo T. Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. Nature Communications, volume 9, Article number: 3663 (2018) https://www.pasteur.fr/fr/centre-medical/fiches-maladies/candidoses