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

JI Robinson, WH Weir, JR Crowley… - The Journal of …, 2019 - Am Soc Clin Investig
JI Robinson, WH Weir, JR Crowley, T Hink, KA Reske, JH Kwon, CAD Burnham
The Journal of Clinical Investigation, 2019Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation