Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis

Moon Seong Baek; Seungil Kim; Won-Young Kim; Mi-Na Kweon; Jin Won Huh

doi:10.3389/fmicb.2023.1140402

Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis

Front Microbiol. 2023 Apr 4:14:1140402. doi: 10.3389/fmicb.2023.1140402. eCollection 2023.

Authors

Moon Seong Baek¹, Seungil Kim², Won-Young Kim¹, Mi-Na Kweon², Jin Won Huh³

Affiliations

¹ Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
² Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients.

Methods: Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed.

Results: CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups.

Conclusion: Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE.

Keywords: carbapenem-resistant Enterobacteriaceae (CRE); intestinal dysbiosis; metabolic networks and pathways; microbiome; short-chain fatty acid.

Grants and funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI18C2383), and by the Chung-Ang University Research Grants in 2022.