Abstract
BackgroundAntibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic.Methods16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (eight cats) or commercially-available synbiotic (eight cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last three days of baseline (days 5–7), treatment (26–28), and recovery (631–633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P < 0.05 was considered significant. The Benjamini & Hochberg’s False Discovery Rate was used to adjust for multiple comparisons.ResultsMedian age was six and five years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26–28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631–633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups.DiscussionCats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.
Highlights
IntroductionAntibiotic administration is associated with profound, and sometimes prolonged, derangements of the fecal microbiome and metabolome of people and animals (De La Cochetière et al, 2010; Dethlefsen et al, 2008; Jakobsson et al, 2010; Suchodolski, 2016b; Suchodolski et al, 2009)
Antibiotic administration is associated with profound, and sometimes prolonged, derangements of the fecal microbiome and metabolome of people and animals (De La Cochetière et al, 2010; Dethlefsen et al, 2008; Jakobsson et al, 2010; Suchodolski, 2016b; Suchodolski et al, 2009). This dysbiosis is believed to be a primary contributor to the development of antibiotic-associated gastrointestinal signs (AAGS), such as hyporexia, vomiting, and diarrhea (Hempel et al, 2012; McFarland, 2008; Videlock & Cremonini, 2012)
Antibiotic-associated gastrointestinal signs occur commonly in cats (Albarellos & Landoni, 2009; Albarellos & Landoni, 1995; Hunter et al, 1995) and people (Hempel et al, 2012; Lenoir-Wijnkoop et al, 2014; McFarland, 2008), and they are an important cause of antibiotic non-compliance (Chan et al, 2012; Jefferds et al, 2002; Kardas et al, 2005; Llor et al, 2013; Muñoz et al, 2014; Pechere et al, 2007)
Summary
Antibiotic administration is associated with profound, and sometimes prolonged, derangements of the fecal microbiome and metabolome of people and animals (De La Cochetière et al, 2010; Dethlefsen et al, 2008; Jakobsson et al, 2010; Suchodolski, 2016b; Suchodolski et al, 2009) This dysbiosis is believed to be a primary contributor to the development of antibiotic-associated gastrointestinal signs (AAGS), such as hyporexia, vomiting, and diarrhea (Hempel et al, 2012; McFarland, 2008; Videlock & Cremonini, 2012). Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with
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