Abstract
ABSTRACT Reduction in antibiotic-associated gastrointestinal signs (AAGS) in people co-administered probiotics is believed to result from shifts in the microbiome and metabolome. Amelioration of AAGS in cats secondary to synbiotic administration has recently been demonstrated. Thus, the aim of this randomized, double-blinded, placebo-controlled trial was to characterize associated changes in the fecal microbiome and metabolome. Sixteen healthy research cats received clindamycin with food, followed 1 h later by either a placebo or synbiotic, daily for 21 days. Fecal samples were collected during baseline, antibiotic administration, and 6 weeks after antibiotic discontinuation. Sequencing of 16S rRNA genes was performed, and mass spectrometry was used to determine fecal metabolomic profiles. Results were compared using mixed-model analyses, with P < 0.05 considered significant. Alpha and beta diversity were altered significantly during treatment, with persistent changes in the Shannon and dysbiosis indices. The relative abundance of Actinobacteria (Adlercreutzia, Bifidobacterium, Collinsella, Slackia), Bacteroidia (Bacteroides, Prevotella), Ruminococcaceae (Faecalibacterium, Ruminococcus), Veillonellaceae (Megamonas, Megasphaera, Phascolarctobacterium) and Erysipelotrichaceae ([Eubacterium]) decreased and relative abundance of Clostridiaceae (Clostridium) and Proteobacteria (Enterobacteriaceae) increased during treatment, followed by variable return to baseline relative abundances. Derangements in short-chain fatty acid (SCFA), bile acid, tryptophan, sphingolipid, polyamine, benzoic acid, and cinnaminic acid pathways occurred with significant group by time, group, and time interactions for 10, 5, and 106 metabolites, respectively. Of particular note were changes related to polyamine synthesis. Further investigation is warranted to elucidate the role of these alterations in prevention of AAGS in cats, people, and other animals treated with synbiotics.
Highlights
Significant differences were found in the fecal microbiome and metabolome of healthy research cats co-administered high dose clindamycin and a placebo or a synbiotic (Proviable-DC®, Nutramax Laboratories Veterinary Sciences, Inc., Lancaster, SC USA) once daily for 21 days in one randomized trial, associated gastrointestinal signs (AAGS) did not differ between groups
We hypothesized that antibiotic-induced changes in the fecal microbiome and metabolomic profiles would differ between treatment groups
Fecal samples were available for eight cats from this group during baseline and recovery but only for four cats at the conclusion of antibiotic administration
Summary
Clindamycin and other antibiotics can cause antibiotic-associated gastrointestinal signs (AAGS) in cats and people. The postulated mechanism for the development of AAGS is derangement of the intestinal microbiome, which has been shown to persist up to 4 years after short-term antibiotic administration in people. Antibiotic administration has been associated with alterations in metabolites with roles in immune function, maintaining enterocyte tight junctions, and glucose homeostasis. Significant differences were found in the fecal microbiome and metabolome of healthy research cats co-administered high dose clindamycin and a placebo or a synbiotic (Proviable-DC®, Nutramax Laboratories Veterinary Sciences, Inc., Lancaster, SC USA) once daily for 21 days in one randomized trial, AAGS did not differ between groups. In a follow-up trial, cats were administered a lower dose of clindamycin, followed 1 h later by either a placebo or higher dose of the same synbiotic. Significant differences were found in the fecal microbiome and metabolome of healthy research cats co-administered high dose clindamycin and a placebo or a synbiotic (Proviable-DC®, Nutramax Laboratories Veterinary Sciences, Inc., Lancaster, SC USA) once daily for 21 days in one randomized trial, AAGS did not differ between groups.. In a follow-up trial, cats were administered a lower dose of clindamycin, followed 1 h later by either a placebo or higher dose of the same synbiotic. Cats receiving the synbiotic had significantly higher food intake, vomited less, and were more likely to complete the initial phase of treatment. Based on these results, we hypothesized that antibiotic-induced changes in the fecal microbiome and metabolomic profiles would differ between treatment groups
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