Metabolomic networks connect host-microbiome processes to human Clostridioides difficile infections

Clostridioides difficile infection (CDI) accounts for a substantial proportion of deaths attributable to antibiotic-resistant bacteria in the United States. Although C. difficile can be an asymptomatic colonizer, its pathogenic potential is most commonly manifested in patients with antibiotic-modifi...

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Bibliographic Details
Published in:The Journal of clinical investigation 2019-09, Vol.129 (9), p.3792-3806
Main Authors: Robinson, John I, Weir, William H, Crowley, Jan R, Hink, Tiffany, Reske, Kimberly A, Kwon, Jennie H, Burnham, Carey-Ann D, Dubberke, Erik R, Mucha, Peter J, Henderson, Jeffrey P
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Amino acids
Antibiotics
Bacteria
Bile
Bile acids
Bile Acids and Salts - chemistry
Biomedical research
Branched chain amino acids
Chromatography
Clostridioides difficile
Clostridium Infections - microbiology
Colonization
Deoxycholic acid
Diarrhea
Diarrhea - microbiology
Enzymes
Fatty acids
Feces
Feces - microbiology
Female
Fermentation
Gas Chromatography-Mass Spectrometry
Gastrointestinal Microbiome
Health aspects
Hospital patients
Humans
Immunoassay
Infection
Infections
Intestine
Laboratories
Least-Squares Analysis
Leucine
Leucine - chemistry
Male
Mass spectrometry
Metabolic Networks and Pathways
Metabolism
Metabolites
Metabolomics
Microbial drug resistance
Microbiomes
Microbiota
Middle Aged
Multivariate Analysis
Principal Component Analysis
Scientific imaging
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Summary:Clostridioides difficile infection (CDI) accounts for a substantial proportion of deaths attributable to antibiotic-resistant bacteria in the United States. Although C. difficile can be an asymptomatic colonizer, its pathogenic potential is most commonly manifested in patients with antibiotic-modified intestinal microbiomes. In a cohort of 186 hospitalized patients, we showed that host and microbe-associated shifts in fecal metabolomes had the potential to distinguish patients with CDI from those with non-C. difficile diarrhea and C. difficile colonization. Patients with CDI exhibited a chemical signature of Stickland amino acid fermentation that was distinct from those of uncolonized controls. This signature suggested that C. difficile preferentially catabolizes branched chain amino acids during CDI. Unexpectedly, we also identified a series of noncanonical, unsaturated bile acids that were depleted in patients with CDI. These bile acids may derive from an extended host-microbiome dehydroxylation network in uninfected patients. Bile acid composition and leucine fermentation defined a prototype metabolomic model with potential to distinguish clinical CDI from asymptomatic C. difficile colonization.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI126905