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Effects of oral Akkermansia muciniphila supplementation in healthy dogs following antimicrobial administration

Maria C. Jugan DVM, MS1, Adam J. Rudinsky DVM, MS2, Alexander Gordon MS3, Denise L. Kramer MS, MSL4, Joshua B. Daniels DVM, PhD5, Oleg Paliy PhD6, Prosper Boyaka PhD7, and Chen Gilor DVM, PhD8
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  • 1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 3 Department of Biochemistry and Molecular Biology, College of Science and Mathematics, Wright State University, Dayton, OH 45435.
  • | 4 Department of Biochemistry and Molecular Biology, College of Science and Mathematics, Wright State University, Dayton, OH 45435.
  • | 5 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 6 Department of Biochemistry and Molecular Biology, College of Science and Mathematics, Wright State University, Dayton, OH 45435.
  • | 7 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 8 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Abstract

OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers of gastrointestinal permeability and epithelial damage following antimicrobial administration in dogs.

ANIMALS 8 healthy adult dogs.

PROCEDURES Dogs were randomly assigned to receive either A muciniphila (109 cells/kg; n = 4) or vehicle (PBS solution; 4) for 6 days following metronidazole administration (12.5 mg/kg, PO, q 12 h for 7 d). After a 20-day washout period, the same dogs received the alternate treatment. After another washout period, experiments were repeated with amoxicillin-clavulanate (13.5 mg/kg, PO, q 12 h) instead of metronidazole. Fecal consistency was scored, a quantitative real-time PCR assay for A muciniphila in feces was performed, and plasma concentrations of cytokeratin-18, lipopolysaccharide, and glucagon-like peptides were measured by ELISA before (T0) and after (T1) antimicrobial administration and after administration of A muciniphila or vehicle (T2).

RESULTS A muciniphila was detected in feces in 7 of 8 dogs after A muciniphila treatment at T2 (3/4 experiments) but not at T0 or T1. After metronidazole administration, mean change in plasma cytokeratin-18 concentration from T1 to T2 was significantly lower with vehicle than with A muciniphila treatment (−0.27 vs 2.4 ng/mL). Mean cytokeratin-18 concentration was lower at T1 than at T0 with amoxicillin-clavulanate. No other significant biomarker concentration changes were detected. Probiotic administration was not associated with changes in fecal scores. No adverse effects were attributed to A muciniphila treatment.

CONCLUSIONS AND CLINICAL RELEVANCE Detection of A muciniphila in feces suggested successful gastrointestinal transit following oral supplementation in dogs. Plasma cytokeratin-18 alterations suggested an effect on gastrointestinal epithelium. Further study is needed to investigate effects in dogs with naturally occurring gastrointestinal disease.

Abstract

OBJECTIVE To measure effects of oral Akkermansia muciniphila administration on systemic markers of gastrointestinal permeability and epithelial damage following antimicrobial administration in dogs.

ANIMALS 8 healthy adult dogs.

PROCEDURES Dogs were randomly assigned to receive either A muciniphila (109 cells/kg; n = 4) or vehicle (PBS solution; 4) for 6 days following metronidazole administration (12.5 mg/kg, PO, q 12 h for 7 d). After a 20-day washout period, the same dogs received the alternate treatment. After another washout period, experiments were repeated with amoxicillin-clavulanate (13.5 mg/kg, PO, q 12 h) instead of metronidazole. Fecal consistency was scored, a quantitative real-time PCR assay for A muciniphila in feces was performed, and plasma concentrations of cytokeratin-18, lipopolysaccharide, and glucagon-like peptides were measured by ELISA before (T0) and after (T1) antimicrobial administration and after administration of A muciniphila or vehicle (T2).

RESULTS A muciniphila was detected in feces in 7 of 8 dogs after A muciniphila treatment at T2 (3/4 experiments) but not at T0 or T1. After metronidazole administration, mean change in plasma cytokeratin-18 concentration from T1 to T2 was significantly lower with vehicle than with A muciniphila treatment (−0.27 vs 2.4 ng/mL). Mean cytokeratin-18 concentration was lower at T1 than at T0 with amoxicillin-clavulanate. No other significant biomarker concentration changes were detected. Probiotic administration was not associated with changes in fecal scores. No adverse effects were attributed to A muciniphila treatment.

CONCLUSIONS AND CLINICAL RELEVANCE Detection of A muciniphila in feces suggested successful gastrointestinal transit following oral supplementation in dogs. Plasma cytokeratin-18 alterations suggested an effect on gastrointestinal epithelium. Further study is needed to investigate effects in dogs with naturally occurring gastrointestinal disease.

Contributor Notes

Dr. Jugan's present address is Upstate Veterinary Specialists, 393 Woods Lake Rd, Greenville, SC 29607. Dr. Daniels' present address is Department of Microbiology, Immunology & Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523. Dr. Gilor's present address is Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

Address correspondence to Dr. Gilor (cgilor@ucdavis.edu).