@article{5dc508402b1445a8aa9dfd0e99a99ca8,
title = "Metabolomic networks connect host-microbiome processes to human Clostridioides difficile infections",
abstract = "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.",
author = "Robinson, {John I.} and Weir, {William H.} and Crowley, {Jan R.} and Tiffany Hink and Reske, {Kimberly A.} and Kwon, {Jennie H.} and Burnham, {Carey Ann D.} and Dubberke, {Erik R.} and Mucha, {Peter J.} and Henderson, {Jeffrey P.}",
note = "Funding Information: Conflict of interest: ERD receives grants from Rebiotix, grants and personal fees from Pfizer and Merck, and personal fees from Valneva, Rebiotix, Achaogen, Biofire, Abbott, and Synthetic Biologics. CDB receives grants from bioMerieux, Cepheid, and Luminex, grants and personal fees from Accelerate Diagnostics, and personal fees from BioRad and the Journal of Clinical Microbiology. Copyright: {\textcopyright} 2019, American Society for Clinical Investigation. Submitted: January 2, 2019; Accepted: June 11, 2019; Published: August 12, 2019. Reference information: J Clin Invest. 2019;129(9):3792–3806. https://doi.org/10.1172/JCI126905. Funding Information: The authors acknowledge funding from the Centers for Disease Control and Prevention's investments to combat antibiotic resistance under award number 200-2016-91939 and a CDC Prevention Epicenters Program Grant (CU54 CK 000162). JHK acknowledges support by the Washington University Institute of Clinical and Translational Sciences (grant no. UL1TR000448) and a sub-award (grant no. KL2TR000450) from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health. We are grateful for helpful conversations with Clifford McDonald and Alison Laufer from the United States Centers for Disease Control. Publisher Copyright: {\textcopyright} 2019, American Society for Clinical Investigation.",
year = "2019",
month = sep,
day = "3",
doi = "10.1172/JCI126905",
language = "English",
volume = "129",
pages = "3792--3806",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
number = "9",
}