Date Published: September 27, 2018
Publisher: Public Library of Science
Author(s): Anna-Lena Ziese, Jan S. Suchodolski, Katrin Hartmann, Kathrin Busch, Alexandra Anderson, Fatima Sarwar, Natalie Sindern, Stefan Unterer, Leandro Araujo Lobo.
The impact of probiotics on dogs with acute hemorrhagic diarrhea syndrome (AHDS) has not been evaluated so far. The study aim was to assess the effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with AHDS in a prospective, placebo-controlled, blinded trial.
Twenty-five dogs with AHDS with no signs of sepsis were randomly divided into a probiotic (PRO; Visbiome, ExeGi Pharma) and placebo group (PLAC). Treatment was administered for 21 days without antibiotics. Clinical signs were evaluated daily from day 0 to day 8. Key bacterial taxa, C. perfringens encoding NetF toxin and enterotoxin were assessed on days 0, 7, 21.
Both groups showed a rapid clinical improvement. In PRO a significant clinical recovery was observed on day 3 (p = 0.008), while in PLAC it was observed on day 4 (p = 0.002) compared to day 0. Abundance of Blautia (p<0.001) and Faecalibacterium (p = 0.035) was significantly higher in PRO on day 7 compared to day 0, while in PLAC the abundance of Faecalibacterium was not significantly higher on any study day and Blautia (p = 0.016) was only significantly higher on day 21 compared to day 0. Abundance of C. perfringens was significantly lower on day 7 (p = 0.011) compared to day 0 in PRO but not in PLAC. Enterotoxin genes were significantly lower in PRO on day 21 (p = 0.028) compared to PLAC. Fecal samples of 57% of all dogs were positive for netF toxin genes on day 0 and the abundance was significantly lower on day 7 compared to day 0 in PRO (p = 0.016) and PLAC (p = 0.031). The probiotic treatment was associated with an accelerated normalization of the intestinal microbiome. Dogs with aseptic AHDS showed a rapid decrease of netF toxin genes and fast clinical recovery in both groups under symptomatic treatment without antibiotics.
Acute hemorrhagic diarrhea syndrome (AHDS) is a common complaint in dogs presented to primary care veterinarians. The etiology is not fully understood, but there is strong evidence that C. perfringens and its toxins play a role in the pathogenesis and are responsible for the intestinal lesions in most dogs diagnosed with AHDS . An increase in fecal abundance of enterotoxigenic C. perfringens has been associated with acute non-hemorrhagic as well as with hemorrhagic diarrhea [2, 3]. Nevertheless, there was no difference found in severity of clinical or laboratory parameters between dogs with AHDS that were either positive or negative for C. perfringens encoding enterotoxin . Recently, novel pore-forming toxins designated as NetE and NetF were identified in a C. perfringens type A strain isolated from a dog with acute hemorrhagic diarrhea, and the cytotoxic effect of NetF could be demonstrated in vitro . In addition, there is a significantly higher prevalence of C. perfringens encoding NetF toxin (netF) in canine AHDS isolates compared to undifferentiated canine diarrheal isolates , and a preliminary study also showed a significant higher abundance of netF in dogs with AHDS compared to healthy dogs or dogs with parvovirosis .
The aim of this study was to evaluate whether probiotic treatment has an impact on the clinical course, the intestinal microbiome and the abundance of C. perfringens and toxigenic C. perfringens in dogs with AHDS. Therefore, dogs with hemorrhagic diarrhea lasting less than three days were included in this trial. Dogs with an underlying disease possibly responsible for hemorrhagic diarrhea or dogs with potential signs of sepsis at clinical presentation or during the study were excluded. Dogs in the probiotic group received a high potency, multi strain, orally administered probiotic powder, which was chosen based on previous studies demonstrating upregulated expression of tight junction proteins and clinical response in dogs with IBD [21, 22].