Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins

Nathan E. Stone, Amalee E. Nunnally, Victor Jimenez, Emily K. Cope, Jason W. Sahl, Krystal Sheridan, Heidie M. Hornstra, Jacob Vinocur, Erik W. Settles, Kyle C. Headley, Charles H.D. Williamson, Jai Ram Rideout, Evan Bolyen, James G Caporaso, Joel Terriquez, Fernando P Monroy, Joseph D. Busch, Paul S Keim, David M Wagner

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAnaerobe
DOIs
StatePublished - Jan 1 2019

Fingerprint

Dysbiosis
Clostridium difficile
Canidae
Infection
Community-Acquired Infections
Tight Junctions
rRNA Genes
Virulence
Sphingobacterium
Homeostasis

Keywords

  • Asymptomatic carriage
  • Bile acid mediated resistance
  • Clostridioides difficile
  • Community-acquired infection
  • Microbial dysbiosis

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins. / Stone, Nathan E.; Nunnally, Amalee E.; Jimenez, Victor; Cope, Emily K.; Sahl, Jason W.; Sheridan, Krystal; Hornstra, Heidie M.; Vinocur, Jacob; Settles, Erik W.; Headley, Kyle C.; Williamson, Charles H.D.; Rideout, Jai Ram; Bolyen, Evan; Caporaso, James G; Terriquez, Joel; Monroy, Fernando P; Busch, Joseph D.; Keim, Paul S; Wagner, David M.

In: Anaerobe, 01.01.2019.

Research output: Contribution to journalReview article

Stone, NE, Nunnally, AE, Jimenez, V, Cope, EK, Sahl, JW, Sheridan, K, Hornstra, HM, Vinocur, J, Settles, EW, Headley, KC, Williamson, CHD, Rideout, JR, Bolyen, E, Caporaso, JG, Terriquez, J, Monroy, FP, Busch, JD, Keim, PS & Wagner, DM 2019, 'Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins', Anaerobe. https://doi.org/10.1016/j.anaerobe.2019.03.017
Stone, Nathan E. ; Nunnally, Amalee E. ; Jimenez, Victor ; Cope, Emily K. ; Sahl, Jason W. ; Sheridan, Krystal ; Hornstra, Heidie M. ; Vinocur, Jacob ; Settles, Erik W. ; Headley, Kyle C. ; Williamson, Charles H.D. ; Rideout, Jai Ram ; Bolyen, Evan ; Caporaso, James G ; Terriquez, Joel ; Monroy, Fernando P ; Busch, Joseph D. ; Keim, Paul S ; Wagner, David M. / Domestic canines do not display evidence of gut microbial dysbiosis in the presence of Clostridioides (Clostridium) difficile, despite cellular susceptibility to its toxins. In: Anaerobe. 2019.
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abstract = "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.",
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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, Jacob

AU - Settles, Erik W.

AU - Headley, Kyle C.

AU - Williamson, Charles H.D.

AU - Rideout, Jai Ram

AU - Bolyen, Evan

AU - Caporaso, James G

AU - Terriquez, Joel

AU - Monroy, Fernando P

AU - Busch, Joseph D.

AU - Keim, Paul S

AU - Wagner, David M

PY - 2019/1/1

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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.

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KW - Asymptomatic carriage

KW - Bile acid mediated resistance

KW - Clostridioides difficile

KW - Community-acquired infection

KW - Microbial dysbiosis

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