Probiotika-Therapie bei Hunden mit Akutem hämorrhagischem Diarrhoesyndrom

Probiotika sind lebende Mikroorganismen, die einen gesundheitlichen Vorteil bringen, wenn sie in ausreichender Menge verabreicht werden (WHO/FAO, 2002). Eine positive Wirkung kann unter anderem durch die Verdrängung von Pathogenen, Immunmodulation, Unterstützung der Darmbarriere und durch Nährstoffbereitstellung erfolgen (DOBSON et al., 2012; ASHRAF und SHAH, 2014; NAGPAL et al., 2018). Positive Effekte einer Probiotika-Therapie konnten bei Hunden mit unterschiedlichen gastrointestinalen Erkrankungen in vorherigen Studien beobachtet werden. Das Akute hämorrhagische Diarrhoesyndrom (AHDS) des Hundes ist eine Erkrankung, die durch das akute Auftreten von blutigem Durchfall gekennzeichnet ist, dem in circa 80 % der Fälle Erbrechen vorausgeht (MORTIER et al., 2015). Unter symptomatischer Therapie, bei der vor allem der Ausgleich der Hypovolämie durch intravenöse Flüssigkeitssubstitution eine zentrale Rolle spielt, zeigen Patienten mit AHDS in der Regel eine schnelle klinische Besserung. Bei Patienten, die keine Anzeichen einer Sepsis haben, ist eine antibiotische Therapie nicht grundsätzlich indiziert (UNTERER et al., 2011). Die Pathophysiologie des AHDS ist derzeit nicht vollständig geklärt, aber Clostridium (C.) perfringens, insbesondere Enterotoxin- und NetF-Toxin-produzierende Stämme scheinen am Krankheitsprozess beteiligt zu sein (MINAMOTO et al., 2014b; UNTERER et al., 2014; GUARD et al., 2015). Das intestinale Mikrobiom spielt als metabolisches und immunologisches Organ eine wichtige Rolle für die Gesundheit des Wirts, indem es unter anderem das Immunsystem moduliert, den Wirt vor Pathogenen schützt und Nahrungsbestandteile verstoffwechselt (BAUER et al., 2006; KAMADA et al., 2013; ROWLAND et al., 2018; TIZARD und JONES, 2018). Patienten mit AHDS weisen, verglichen mit gesunden Hunden, eine intestinale Dysbiose auf. Eine Normalisierung der intestinalen Dysbiose erscheint aufgrund der wichtigen Funktionen des Mikrobioms sinnvoll. Ziel dieser prospektiven, placebokontrollierten, randomisierten Studie war es herauszufinden, welchen Effekt ein Probiotikum auf den klinischen Verlauf, das fäkale Mikrobiom und toxinbildende C. perfringens bei Hunden mit AHDS hat

Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea

Introduction 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. Methods 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. Results 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). Conclusion 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

Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole

The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT;n = 11) or oral metronidazole (MET;n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC;n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI;increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs

Correction: Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea.

[This corrects the article DOI: 10.1371/journal.pone.0204691.]