Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.

BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.

Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion. OBJECTIVES: Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death. ANIMALS: Thirty-one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs. METHODS: Antithrombin and α2 -antiplasmin activity (ATA and α2 AP, respectively) and concentrations of α1 -proteinase inhibitor (α1 PI), α2 -macroglobulin (α2 MG), C-reactive protein (CRP), interleukins (ILs)-2,6,8 and tumor necrosis factor-α (TNF-α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems. RESULTS: Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL-6, and TNF-α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL-2, IL-8, α1 PI, and α2 AP concentrations did not differ between groups. Serum α2 MG concentration was not reliably detected. Serum cPLI, CRP, and IL-6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL-6 concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2 AP and α1 PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.

Fecal short-chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy.

BACKGROUND: Accumulating evidence shows an important relationship between the gastrointestinal (GI) microbiota and host health. Microbial metabolites are believed to play a critical role in host-microbial interactions. Short-chain fatty acids (SCFAs) are major end products of bacterial carbohydrate fermentation in the intestinal tract. Decreased concentrations of SCFAs have been observed in humans with GI disease. However, large-scale clinical data in dogs are lacking. HYPOTHESIS/OBJECTIVE: To evaluate fecal concentrations of SCFAs and the fecal microbiota in healthy control (HC) dogs and dogs with chronic enteropathy (CE). ANIMALS: Forty-nine privately owned HC dogs and 73 dogs with CE. METHODS: Prospective cohort study. Fecal concentrations of SCFAs were measured using gas chromatography/mass spectrometry. Illumina sequencing and quantitative real-time polymerase chain reaction were utilized to evaluate the fecal microbiota. RESULTS: Fecal concentrations (median [range] µmol/g of dry matter) of acetate were lower (P = .03) in dogs with CE (185.8 [20.1-1042.1]) than in HC dogs (224.0 [87.7-672.8]). Propionate were also lower (P < .001) in dogs with CE (46.4 [0.4-227.9]) than in HC dogs (105.9 [1.6-266.9]). Moreover, total SCFAs were lower (P = .005) in dogs with CE (268.1 [21.8-1378.2]) than in HC dogs (377.2 [126.6-927.0]). Dysbiosis in dogs with CE was characterized by decreased bacterial diversity and richness, distinct microbial community clustering compared with that in HC dogs, and a higher dysbiosis index. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CE had an altered fecal SCFA concentration accompanied by significant changes of the fecal microbiota.