Gut microbial and metabolic features associated with Clostridioides difficile infection recurrence in children

Author:

Li Xiaolu1,Xiao Fangfei1,Wang Xufei1,Ye Lin1,Xiao Yongmei1,Li Dan1,Zhang Ting12,Wang Yizhong12

Affiliation:

1. Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China

2. Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University , Shanghai , China

Abstract

Abstract Background Recurrent Clostridioides difficile (C. difficile) infection (rCDI) is a critical clinical issue due to the increase in incidence and difficulty in treatment. We aimed to identify gut microbial and metabolic features associated with disease recurrence in a group of pediatric CDI patients. Methods A total of 84 children with primary CDI were prospectively enrolled in the study. Fecal samples collected at the initial diagnosis were subjected to 16S rRNA gene sequencing and targeted metabolomics analysis to profile the bacterial composition and metabolome. Results Twenty-six (26/84, 31.0%) pediatric CDI patients experienced recurrence. The alpha diversity of the fecal microbiota was significantly lower in the recurrent group than in the nonrecurrent group, and the beta diversity was different from that of the nonrecurrent group. Taxonomic profiles revealed that the relative abundances of multiple bacterial taxa significantly differed between the recurrent and nonrecurrent groups. Linear discriminant analysis (LDA) effect size (LEfSe) analysis identified several bacterial genera that discriminated between recurrent and nonrecurrent groups, including Parabacteroides, Coprococcus, Disalister and Clostridium. Recurrent bacteria presented lower abundances of several short-chain fatty acid (SCFA)-producing bacteria (Faecalibacterium, Butyricicoccus, Clostridium, Roseburia, and Ruminococcus), which were correlated with reduced fecal SCFA levels. In addition, several bile acids (BAs), including lithochalic acid (LCA), 12-ketoLCA, trihydroxycholestanoic acid (3-DHCA), and deoxycholic acid (DCA), were decreased in recurrent patients. Conclusions Our study suggests that the differing gut microbiota profiles in pediatric CDI patients may contribute to disease recurrence by modulating SCFA concentrations and BA profiles. The gut microbiota and metabolite signatures may be used to predict disease recurrence in children with CDI.

Publisher

Oxford University Press (OUP)

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