Gut microbiome dynamics and Enterobacterales infection in liver transplant patients: a prospective observational study (metagenomics)
Background and Aims: To investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection and non-CRE infection development within 2 months after liver transplant (LT).Methods: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. GM was profiled by 16S rRNA amplicon sequencing of rectal swab taken on the day of transplantation and fecal samples collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in GM in the following groups: i) CRE carriers developing CRE infection (CRE_I); ii) CRE carriers not developing infection (CRE_UI); iii) non-CRE carriers developing microbial infection (INF); and iv) non-CRE carriers not developing infection (NEG).Results: Overall, 97 patients were enrolled and 91 provided fecal samples. Of these, 5, 9, 22 and 55 patients were classified as CRE_I, CRE_UI, INF and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual overrepresentation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I than in NEG patients even before LT, as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.Conclusions: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.