Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection

Abstract

Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of _Clostridioides difficile _infections (rCDI) and can also be useful for other microbiota-related diseases. We study the effect of FMT in patients with rCDI on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. Based on MDR culture (n=87 patients), we see a decrease in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 three weeks after FMT = 11.5%). Metagenomic sequencing (n=63 patients) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to healthy donors (n=11 donors). Furthermore, plasmid predictions in metagenomic data indicate that rCDI patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long-term (n=22 patients), the recipients’ resistomes became more donor-like, suggesting that microbiota restoration continues after 3 weeks post-FMT. Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is similar to healthy donors, and potential pathogens are either lost or forced to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, FMT may lead to a more stable and resilient microbiota composition.