TY - JOUR
T1 - Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins
AU - Stone, Nathan E.
AU - Nunnally, Amalee E.
AU - Jimenez, Victor
AU - Cope, Emily K.
AU - Sahl, Jason W.
AU - Sheridan, Krystal
AU - Hornstra, Heidie M.
AU - Vinocur, J.
AU - Settles, Erik W.
AU - Headley, Kyle C.
AU - Williamson, Charles H.D.
AU - Rideout, Jai Ram
AU - Bolyen, Evan
AU - Caporaso, J. Gregory
AU - Terriquez, Joel
AU - Monroy, Fernando P.
AU - Busch, Joseph D.
AU - Keim, Paul
AU - Wagner, David M.
N1 - Funding Information:
This work was funded by the NAU Technology & Research Initiative Fund (TRIF) , the Flinn Foundation , the NAU Cowden Endowment , and in part by NSF Award [grant number 1565100 ] to JGC.
Funding Information:
This work was funded by the NAU Technology & Research Initiative Fund (TRIF), the Flinn Foundation, the NAU Cowden Endowment, and in part by NSF Award [grant number 1565100] to JGC. We thank Irene Zhang, Shari Kyman, and Arron Shiffer at the NAU Pathogen and Microbiome Institute for providing additional expertise with 16S rRNA data generation and analyses. We also thank Dr. Anna Seekatz for providing insights into the Healthy Human 16S rRNA dataset used in this study.
Publisher Copyright:
© 2019 The Authors
PY - 2019/8
Y1 - 2019/8
N2 - Clostridioides difficile infection (CDI) is an emerging public health threat and C. difficile is the most common cause of antimicrobial-associated diarrhea worldwide and the leading cause of hospital-associated infections in the US, yet the burden of community-acquired infections (CAI) is poorly understood. Characterizing C. difficile isolated from canines is important for understanding the role that canines may play in CAI. In addition, several studies have suggested that canines carry toxigenic C. difficile asymptomatically, which may imply that there are mechanisms responsible for resistance to CDI in canines that could be exploited to help combat human CDI. To assess the virulence potential of canine-derived C. difficile, we tested whether toxins TcdA and TcdB (hereafter toxins) derived from a canine isolate were capable of causing tight junction disruptions to colonic epithelial cells. Additionally, we addressed whether major differences exist between human and canine cells regarding C. difficile pathogenicity by exposing them to identical toxins. We then examined the canine gut microbiome associated with C. difficile carriage using 16S rRNA gene sequencing and searched for deviations from homeostasis as an indicator of CDI. Finally, we queried 16S rRNA gene sequences for bacterial taxa that may be associated with resistance to CDI in canines. Clostridioides difficile isolated from a canine produced toxins that reduced tight junction integrity in both human and canine cells in vitro. However, canine guts were not dysbiotic in the presence of C. difficile. These findings support asymptomatic carriage in canines and, furthermore, suggest that there are features of the gut microbiome and/or a canine-specific immune response that may protect canines against CDI. We identified two biologically relevant bacteria that may aid in CDI resistance in canines: 1) Clostridium hiranonis, which synthesizes secondary bile acids that have been shown to provide resistance to CDI in mice; and 2) Sphingobacterium faecium, which produces sphingophospholipids that may be associated with regulating homeostasis in the canine gut. Our findings suggest that canines may be cryptic reservoirs for C. difficile and, furthermore, that mechanisms of CDI resistance in the canine gut could provide insights into targeted therapeutics for human CDI.
AB - Clostridioides difficile infection (CDI) is an emerging public health threat and C. difficile is the most common cause of antimicrobial-associated diarrhea worldwide and the leading cause of hospital-associated infections in the US, yet the burden of community-acquired infections (CAI) is poorly understood. Characterizing C. difficile isolated from canines is important for understanding the role that canines may play in CAI. In addition, several studies have suggested that canines carry toxigenic C. difficile asymptomatically, which may imply that there are mechanisms responsible for resistance to CDI in canines that could be exploited to help combat human CDI. To assess the virulence potential of canine-derived C. difficile, we tested whether toxins TcdA and TcdB (hereafter toxins) derived from a canine isolate were capable of causing tight junction disruptions to colonic epithelial cells. Additionally, we addressed whether major differences exist between human and canine cells regarding C. difficile pathogenicity by exposing them to identical toxins. We then examined the canine gut microbiome associated with C. difficile carriage using 16S rRNA gene sequencing and searched for deviations from homeostasis as an indicator of CDI. Finally, we queried 16S rRNA gene sequences for bacterial taxa that may be associated with resistance to CDI in canines. Clostridioides difficile isolated from a canine produced toxins that reduced tight junction integrity in both human and canine cells in vitro. However, canine guts were not dysbiotic in the presence of C. difficile. These findings support asymptomatic carriage in canines and, furthermore, suggest that there are features of the gut microbiome and/or a canine-specific immune response that may protect canines against CDI. We identified two biologically relevant bacteria that may aid in CDI resistance in canines: 1) Clostridium hiranonis, which synthesizes secondary bile acids that have been shown to provide resistance to CDI in mice; and 2) Sphingobacterium faecium, which produces sphingophospholipids that may be associated with regulating homeostasis in the canine gut. Our findings suggest that canines may be cryptic reservoirs for C. difficile and, furthermore, that mechanisms of CDI resistance in the canine gut could provide insights into targeted therapeutics for human CDI.
KW - Asymptomatic carriage
KW - Bile acid mediated resistance
KW - Clostridioides difficile
KW - Community-acquired infection
KW - Microbial dysbiosis
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U2 - 10.1016/j.anaerobe.2019.03.017
DO - 10.1016/j.anaerobe.2019.03.017
M3 - Review article
C2 - 30946985
AN - SCOPUS:85063880543
SN - 1075-9964
VL - 58
SP - 53
EP - 72
JO - Anaerobe
JF - Anaerobe
ER -