Longitudinal analysis of the rectal microbiome in dogs with diabetes mellitus after initiation of insulin therapy.

There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.

Short and long-term effects of a synbiotic on clinical signs, the fecal microbiome, and metabolomic profiles in healthy research cats receiving clindamycin: a randomized, controlled trial.

BACKGROUND: Antibiotic-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. METHODS: 16 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. RESULTS: Median 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. DISCUSSION: Cats 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.