TY - JOUR
T1 - Dietary fat promotes antibiotic-induced Clostridioides difficile mortality in mice
AU - Hazleton, Keith Z.
AU - Martin, Casey G.
AU - Orlicky, David J.
AU - Arnolds, Kathleen L.
AU - Nusbacher, Nichole M.
AU - Moreno-Huizar, Nancy
AU - Armstrong, Michael
AU - Reisdorph, Nichole
AU - Lozupone, Catherine A.
N1 - Funding Information:
We would like to thank Jordi Lanis and Sean Colgan for their advice on the employed CDI mouse model and Sally Stabler and Whitney Phinney for their assistance in measuring SCFAs. We also appreciate the contribution to this research made by E. Erin Smith, TL(ASCP)CMQIHC, Jenna Van Der Volgen, HT(ASCP)CM, Allison Quador, HTL(ASCP)CM, and Jessica Arnold HTL(ASCP)CM of the University of Colorado for the histology analyses. This work was supported by NIH U01 AI150589. Additional support was provided by the University of Colorado Department of Medicine’s Outstanding Early Career Science Award program as well as support to Keith Hazleton from the Institutional Training Grant for Pediatric Gastroenterology from NIDDK (5T32-DK067009-12), Clinical Fellow Awards from the Cystic Fibrosis Foundation (HAZLET18DO and HAZLET19DO) and The Judith Sondheimer Pediatric GI Fellow Research Fund. Kathleen Arnolds was supported by T32-AI007405 Training Program in Immunology. High-performance computing was supported by a cluster at the University of Colorado Boulder funded by the National Institutes of Health 1S10OD012300. The Denver Histology Shared Resource is supported in part by the Cancer Center Support Grant (P30CA046934).
Funding Information:
We would like to thank Jordi Lanis and Sean Colgan for their advice on the employed CDI mouse model and Sally Stabler and Whitney Phinney for their assistance in measuring SCFAs. We also appreciate the contribution to this research made by E. Erin Smith, TL(ASCP)CMQIHC, Jenna Van Der Volgen, HT(ASCP)CM, Allison Quador, HTL(ASCP)CM, and Jessica Arnold HTL(ASCP)CM of the University of Colorado for the histology analyses. This work was supported by NIH U01 AI150589. Additional support was provided by the University of Colorado Department of Medicine?s Outstanding Early Career Science Award program as well as support to Keith Hazleton from the Institutional Training Grant for Pediatric Gastroenterology from NIDDK (5T32-DK067009-12), Clinical Fellow Awards from the Cystic Fibrosis Foundation (HAZLET18DO and HAZLET19DO) and The Judith Sondheimer Pediatric GI Fellow Research Fund. Kathleen Arnolds was supported by T32-AI007405 Training Program in Immunology. High-performance computing was supported by a cluster at the University of Colorado Boulder funded by the National Institutes of Health 1S10OD012300. The Denver Histology Shared Resource is supported in part by the Cancer Center Support Grant (P30CA046934).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea, and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber “Western-type” diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals.
AB - Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea, and emerging evidence has linked dietary components with CDI pathogenesis, suggesting that dietary modulation may be an effective strategy for prevention. Here, we show that mice fed a high-fat/low-fiber “Western-type” diet (WD) had dramatically increased mortality in a murine model of antibiotic-induced CDI compared to a low-fat/low-fiber (LF/LF) diet and standard mouse chow controls. We found that the WD had a pro- C. difficile bile acid composition that was driven in part by higher levels of primary bile acids that are produced to digest fat, and a lower level of secondary bile acids that are produced by the gut microbiome. This lack of secondary bile acids was associated with a greater disturbance to the gut microbiome with antibiotics in both the WD and LF/LF diet compared to mouse chow. Mice fed the WD also had the highest level of toxin TcdA just prior to the onset of mortality, but not of TcdB or increased inflammation. These findings indicate that dietary intervention to decrease fat may complement previously proposed dietary intervention strategies to prevent CDI in high-risk individuals.
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U2 - 10.1038/s41522-022-00276-1
DO - 10.1038/s41522-022-00276-1
M3 - Article
C2 - 35365681
AN - SCOPUS:85127517971
VL - 8
JO - npj Biofilms and Microbiomes
JF - npj Biofilms and Microbiomes
SN - 2055-5008
IS - 1
M1 - 15
ER -