Short- and long-term effects of amoxicillin/clavulanic acid or doxycycline on the gastrointestinal microbiome of growing cats

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Authors

Stavroulaki, Evangelia M.
Suchodolski, Jan S.
Pilla, Rachel
Fosgate, Geoffrey Theodore
Sung, Chi-Hsuan
Lidbury, Jonathan
Steiner, Jorg M.
Xenoulis, Panagiotis G.

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Publisher

Public Library of Science

Abstract

Antibiotic treatment in early life influences gastrointestinal (GI) microbial composition and function. In humans, the resultant intestinal dysbiosis is associated with an increased risk for certain diseases later in life. The objective of this study was to determine the temporal effects of antibiotic treatment on the GI microbiome of young cats. Fecal samples were collected from cats randomly allocated to receive either amoxicillin/clavulanic acid (20 mg/kg q12h) for 20 days (AMC group; 15 cats) or doxycycline (10 mg/kg q24h) for 28 days (DOX group;15 cats) as part of the standard treatment of upper respiratory tract infection. In addition, feces were collected from healthy control cats (CON group;15 cats). All cats were approximately two months of age at enrolment. Samples were collected on days 0 (baseline), 20 or 28 (AMC and DOX, respectively; last day of treatment), 60, 120, and 300. DNA was extracted and sequencing of the 16S rRNA gene and qPCR assays were performed. Fecal microbial composition was different on the last day of treatment for AMC cats, and 1 month after the end of antibiotic treatment for DOX cats, compared to CON cats. Species richness was significantly greater in DOX cats compared to CON cats on the last day of treatment. Abundance of Enterobacteriales was increased, and that of Erysipelotrichi was decreased in cats of the AMC group on the last day of treatment compared to CON cats. The abundance of the phylum Proteobacteria was increased in cats of the DOX group on days 60 and 120 compared to cats of the CON group. Only minor differences in abundances between the treatment groups and the control group were present on day 300. Both antibiotics appear to delay the developmental progression of the microbiome, and this effect is more profound during treatment with amoxicillin/clavulanic acid and one month after treatment with doxycycline. Future studies are required to determine if these changes influence microbiome function and whether they have possible effects on disease susceptibility in cats.

Description

S1 Fig. Beta diversity indices among groups. A) Principal Coordinate Analysis of unweighted UniFrac distances of 16S rRNA genes representing the difference in microbial communities among cats treated with amoxicillin clavulanic acid (blue circles), cats treated with doxycycline (yellow circles), and healthy control cats (red circles) on days 20/28 (last day of treatment), 60, 120, and 300. B) Principal Coordinate Analysis of weighted UniFrac distances of 16S rRNA genes representing the difference in microbial communities among cats treated with amoxicillin clavulanic acid (blue circles), cats treated with doxycycline (yellow circles), and healthy control cats (red circles) on days 20/28 (last day of treatment), 60, 120, and 300.
S2 Fig. Rarefaction curves for A) Chao1, B) Observed ASVs, and C) Shannon Index.
S1 Table. Clinical data of cats participating to the study.
S2 Table. Alpha diversity metrics (mean ± standard deviation) with summary statistics; CON, healthy cats that did not receive antibiotics; AMC, cats treated with amoxicillin/clavulanic acid for 20 days; DOX, cats treated with doxycycline for 28 days.
S3 Table. Beta diversity differences based on ANOSIM analysis. CON, healthy cats that did not receive antibiotics; AMC, cats treated with amoxicillin/clavulanic acid for 20 days; DOX, cats treated with doxycycline for 28 days.
S4 Table. Beta diversity differences based on PERMANOVA analysis. CON, healthy cats that did not receive antibiotics; AMC, cats treated with amoxicillin/clavulanic acid for 20 days; DOX, cats treated with doxycycline for 28 days.
S5 Table. Summary statistics of sequencing data describing the mean percent and standard deviation of sequences belonging to antibiotic-treated (AMC and DOX groups) and healthy (CON group) cats.
S6 Table. Summary statistics of qPCR data describing the mean log abundance and standard deviation of bacterial groups belonging to antibiotic-treated (AMC and DOX groups) and healthy (CON group) cats.

Keywords

Cats, Treatment, Doxycycline, Temporal effects, Antibiotic treatment, Gastrointestinal microbiome

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Citation

Stavroulaki, E.M., Suchodolski, J.S., Pilla, R., Fosgate, G.T., Sung, C.-H., Lidbury, J.A. et al. (2021) Short- and long-term effects of amoxicillin/clavulanic acid or doxycycline on the gastrointestinal microbiome of growing cats. PLoS ONE 16(12): e0253031. https://DOI.org/10.1371/journal.pone.0253031.