Dataset Information

Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host.

ABSTRACT: Clostridioides difficile is the leading cause of nosocomial intestinal infections in the United States. Ingested C. difficile spores encounter host bile acids and other cues that are necessary for germinating into toxin-producing vegetative cells. While gut microbiota disruption (often by antibiotics) is a prerequisite for C. difficile infection (CDI), the mechanisms C. difficile employs for colonization remain unclear. Here, we pioneered the application of imaging mass spectrometry to study how enteric infection changes gut metabolites. We find that CDI induces an influx of bile acids into the gut within 24 h of the host ingesting spores. In response, the host reduces bile acid biosynthesis gene expression. These bile acids drive C. difficile outgrowth, as mice receiving the bile acid sequestrant cholestyramine display delayed colonization and reduced germination. Our findings indicate that C. difficile may facilitate germination upon infection and suggest that altering flux through bile acid pathways can modulate C. difficile outgrowth in CDI-prone patients.

SUBMITTER: Wexler AG

PROVIDER: S-EPMC8445666 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host.

Wexler Aaron G AG Guiberson Emma R ER Beavers William N WN Shupe John A JA Washington M Kay MK Lacy D Borden DB Caprioli Richard M RM Spraggins Jeffrey M JM Skaar Eric P EP

Cell reports 20210901 10

Clostridioides difficile is the leading cause of nosocomial intestinal infections in the United States. Ingested C. difficile spores encounter host bile acids and other cues that are necessary for germinating into toxin-producing vegetative cells. While gut microbiota disruption (often by antibiotics) is a prerequisite for C. difficile infection (CDI), the mechanisms C. difficile employs for colonization remain unclear. Here, we pioneered the application of imaging mass spectrometry to study how ...[more]

PMID: 34496241

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Project description:Diarrheal disease, a major cause of morbidity and mortality in dairy calves, is strongly associated with the health and composition of the gut microbiota. Clostridioides difficile is an opportunistic pathogen that proliferates and can produce enterotoxins when the host experiences gut dysbiosis. However, even asymptomatic colonization with C. difficile can be associated with differing degrees of microbiota disruption in a range of species, including people, swine, and dogs. Little is known about the interaction between C. difficile and the gut microbiota in dairy calves. In this study, we sought to define microbial features associated with C. difficile colonization in pre-weaned dairy calves less than 2 weeks of age. We characterized the fecal microbiota of 80 calves from 23 different farms using 16S rRNA sequencing and compared the microbiota of C. difficile-positive (n = 24) and C. difficile-negative calves (n = 56). Farm appeared to be the greatest source of variability in the gut microbiota. When controlling for calf age, diet, and farm location, there was no significant difference in Shannon alpha diversity (P = 0.50) or in weighted UniFrac beta diversity (P = 0.19) between C. difficile-positive and-negative calves. However, there was a significant difference in beta diversity as assessed using Bray-Curtiss diversity (P = 0.0077), and C. difficile-positive calves had significantly increased levels of Ruminococcus (gnavus group) (Adj. P = 0.052), Lachnoclostridium (Adj. P = 0.060), Butyricicoccus (Adj. P = 0.060), and Clostridium sensu stricto 2 compared to C. difficile-negative calves. Additionally, C. difficile-positive calves had fewer microbial co-occurrences than C. difficile-negative calves, indicating reduced bacterial synergies. Thus, while C. difficile colonization alone is not associated with dysbiosis and is therefore unlikely to result in an increased likelihood of diarrhea in dairy calves, it may be associated with a more disrupted microbiota.

Dataset Information

Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host.

Publications

Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host.

Similar Datasets

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