Multi-omics analysis of hospital-acquired diarrhoeal patients reveals biomarkers of enterococcal proliferation and Clostridioides difficile infection

• Published in: Nature communications 2023-11, Vol.14 (1), p.7737-7737, Article 7737
• Main Authors: Bosnjak, Marijana, Karpe, Avinash V., Van, Thi Thu Hao, Kotsanas, Despina, Jenkin, Grant A., Costello, Samuel P., Johanesen, Priscilla, Moore, Robert J., Beale, David J., Srikhanta, Yogitha N., Palombo, Enzo A., Larcombe, Sarah, Lyras, Dena
• Format: Article
• Language: English
• Subjects: 45/23; 45/43; 45/91; 631/326; 631/326/22/1290; 692/4020/1503; Amino acids; Antibiotic resistance; Antibiotics; Biomarkers; Clostridioides difficile; Decarboxylation; Diarrhea; Dysbacteriosis; Fermentation; Gas chromatography; Gene sequencing; Hospitals; Humanities and Social Sciences; Intestinal microflora; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Microbiota; Microorganisms; multidisciplinary; Patients; rRNA; Science; Science (multidisciplinary); Tyrosine; Vancomycin
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43671-8

Hospital-acquired diarrhoea (HAD) is common, and often associated with gut microbiota and metabolome dysbiosis following antibiotic administration. Clostridioides difficile is the most significant antibiotic-associated diarrhoeal (AAD) pathogen, but less is known about the microbiota and metabolome associated with AAD and C. difficile infection (CDI) with contrasting antibiotic treatment. We characterised faecal microbiota and metabolome for 169 HAD patients (33 with CDI and 133 non-CDI) to determine dysbiosis biomarkers and gain insights into metabolic strategies C. difficile might use for gut colonisation. The specimen microbial community was analysed using 16 S rRNA gene amplicon sequencing, coupled with untargeted metabolite profiling using gas chromatography-mass spectrometry (GC-MS), and short-chain fatty acid (SCFA) profiling using GC-MS. AAD and CDI patients were associated with a spectrum of dysbiosis reflecting non-antibiotic, short-term, and extended-antibiotic treatment. Notably, extended antibiotic treatment was associated with enterococcal proliferation (mostly vancomycin-resistant Enterococcus faecium ) coupled with putative biomarkers of enterococcal tyrosine decarboxylation. We also uncovered unrecognised metabolome dynamics associated with concomitant enterococcal proliferation and CDI, including biomarkers of Stickland fermentation and amino acid competition that could distinguish CDI from non–CDI patients. Here we show, candidate metabolic biomarkers for diagnostic development with possible implications for CDI and vancomycin-resistant enterococci (VRE) treatment. Antibiotics can cause hospital-acquired diarrhoea, resulting in gut microbiota and metabolome changes. Here, the authors study the faecal microbiota and metabolome of 169 patients, offering insights into these changes, and identified biomarkers for diagnostics.