Abstract

Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.

Highlights

  • Carbapenem-resistant Enterobacteriaceae (CRE) is an urgent antibiotic threat due to high infection-associated mortality, limited therapeutic options, and potential to rapidly spread between bacterial species [1,2]

  • The relative abundance of Klebsiella was higher in the late decolonization carriers (LDC) group than in the early decolonization carriers (EDC)

  • Bacteroidetes can prevent the colonization of K. pneumoniae in the gut by fortifying the gut immune barrier via IL-36 and macrophages [41]. These results indicated that the gut microbiota was different between the EDC and LDC groups prior to fecal microbiota transplantation (FMT), and this difference could affect the timing of decolonization after FMT

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Summary

Introduction

Carbapenem-resistant Enterobacteriaceae (CRE) is an urgent antibiotic threat due to high infection-associated mortality, limited therapeutic options, and potential to rapidly spread between bacterial species [1,2]. The carriage rates of extended spectrum beta-lactamase (ESBL) or CRE were 75.2% at 3 months, 55.3% at 6 months, and. 35.2% at 12 months, after initial identification [3]. Short-term antibiotic therapy for the decolonization of antibiotic-resistant bacteria (ARB) could reduce carriage during therapy, its long-term effects are unclear [3]. Pathogens can acquire resistance to antibiotics, and side effects of the antibiotics on gut microbiota, including increased susceptibility to 4.0/).

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