Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study

Background & Aims: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenemresistant 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. The GM was pro filed through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were 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 the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG). Results: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classi fied 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 over -representation of Klebsiella and Enterococcus . The proportions of Klebsiella were signi ficantly higher in CRE_I patients than in NEG patients even before LT, serving 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 pro filing before LT could improve patient strati fication and risk prediction and guide early GM -based intervention strategies to reduce infectious complications and improve overall prognosis. Impact and implications: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial -resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM pro filing could improve patient stratification and risk prediction and guide early GM -based intervention strategies to reduce infectious complications and improve overall prognosis. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).