Bacteriophages play a key role in the eradication of Clostridium difficile

Vignette

Treatment of Clostridium difficile infections was given new momentum by the progress of fecal microbiota transplants. Researchers from the University of Hong-Kong have demonstrated the little-known role of bacteriophages in this procedure.

 

Fecal microbiota transplant (FMT) has demonstrated greater efficacy than first line antibiotic therapy with vancomycin in the treatment of C. difficile infections. The curative mechanisms are still poorly understood and cannot be reduced solely to the restoration of bacterial diversity: according to this study, intestinal viruses might play a major role. Comparison of healthy and infected subjects (including those treated by FMT or antibiotic therapy) revealed the role of viruses, particularly bacteriophages. A preliminary FMT study had shown that the transfer of sterile fecal samples had been effective in eliminating symptoms. Non-bacterial elements are therefore thought to contribute to the restoration of a normal intestinal microenvironment.

Viral dysbiosis associated with C. difficile

Study of the intestinal virome showed that Caudovirales bacteriophages were the most abundant virus family in both the group of subjects with the infection and the healthy control group. Subjects suffering from a C. difficile infection however displayed a greater abundance of Caudovirales, but otherwise lower diversity and abundance compared to controls. The abundance and diversity of Microviridae were decreased in infected subjects while the proportion of Anelloviridae was increased. These results clearly show the existence of a dysbiosis of the intestinal virome associated with Clostridium. The authors specify that the deterioration in viral composition observed in other infectious diarrheas is different, suggesting a microorganism-specific dysbiosis.

Caudovirales are important for recovery

The nine subjects treated by FMT were monitored over time, which allowed FMT to be associated with changes in both the intestinal virome and the bacterial microbiota and to observe a decrease in Caudovirales and an increase in Microviridae, reaching a composition close to that observed in healthy subjects. Moreover, recovery was observed when the donor sample contained a higher concentration of Caudovirales, enabling the authors to suggest that these bacteriophages play a positive role in the success of FMT. The quantity and proportion of Caudovirales in the donor sample were also associated with an absence of recurrence and long-term negative results from stool culture tests.

The effect of vancomycin on the virome and microbiome

Vancomycin, on the other hand, produced almost no change in the diversity and richness of Caudovirales, demonstrating the minimal effect of antibiotics on the intestinal viral community. Patients who received vancomycin benefited from a restoration of their bacterial communities, without restoration of the virome and with a higher recurrence rate. Re-establishing a bacterial microbiota, but also a virome closer to that of healthy subjects seems to be decisive in eradicating  Clostridium difficile infections. The results suggest that bacteriophages could play a major role in microbial ecology and have a potential therapeutic impact to be used in diseases for which FMT is less effective.

 

Sources:

T. Zuo et al., « Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome », Gut, vol. 67, no 4, p. 634‑643, avr. 2018.