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Histologic features of small intestine sections of dogs with LPE. Panel a: Duodenal mucosa of a dog enrolled in MET group (CIBDAI score 11 at D0) with severe lymphoplasmacytic inflammation. The infiltrate of inflammatory cells is extending from the tip of the villi, through the lamina propria, to the muscularis mucosae (haematoxylin and eosin; 20×). Panel b: Duodenal mucosa of a dog enrolled in RIF group (CIBDAI score 3 at D0), with moderate lymphoplasmacytic inflammation. The villi are blunted, and the inflammatory cells are scattered into the lamina propria (haematoxylin and eosin; 40×)
Source publication
Background
A clinical trial was conducted in order to assess the efficacy of rifaximin, a broad-spectrum antibiotic with negligible gastrointestinal absorption, in comparison with metronidazole, a commonly employed antimicrobial drug, in dogs with chronic enteropathy. Twenty-four pet dogs were randomly enrolled into two different groups: MET group...
Context in source publication
Context 1
... formalin, were processed according to an automatised method (Tissue-Tek Xpress 120, Sakura Finetek Europe B.V., Flemingweg, the Netherlands). Serial paraffin sections (2 μm) were then prepared, and stained with haematoxylin and eosin for morphological examination. Histologic evaluation was performed by two observers, blind to the treatment (Fig. ...
Citations
... The condition profoundly affects the dog's health and quality of life. Fortunately, several forms of treatment are available for CE, which may involve dietary changes [2], prebiotics and probiotics [3][4][5], antibiotics [6,7], or steroids [8,9]. The course of treatment depends on whether the enteropathy is classified as antibiotic-responsive (ARE), immunosuppressant-responsive (IRE), food-responsive (FRE), or non-responsive (NRE) [1,10,11]. ...
Simple Summary
We report on the changes observed in the microbiomes of fifty-four dogs that received fecal transplants (FMTs) in the form of oral capsules for their chronic vomiting, diarrhea, and/or constipation. We found that the relative abundances of short-chain fatty acid producing bacteria increased after FMT. The microbiome compositions of dogs before and after FMT were associated with the diet and antibiotic history. Furthermore, we found that certain groups of donor bacteria were more commonly shared with the FMT recipient. Lastly, our data suggested that a high degree of overlap between the microbiome of the donor and that of the recipient was negatively associated with bacterial engraftment, and could be an important factor to consider when evaluating the impact of FMTs on the host and its microbiome.
Abstract
Fecal microbiota transplants (FMTs) have been successful at treating digestive and skin conditions in dogs. The degree to which the microbiome is impacted by FMT in a cohort of dogs has not been thoroughly investigated. Using 16S rRNA gene sequencing, we document the changes in the microbiome of fifty-four dogs that took capsules of lyophilized fecal material for their chronic diarrhea, vomiting, or constipation. We found that the relative abundances of five bacterial genera (Butyricicoccus, Faecalibacterium, Fusobacterium, Megamonas, and Sutterella) were higher after FMT than before FMT. Fecal microbiome alpha- and beta-diversity were correlated with kibble and raw food consumption, and prior antibiotic use. On average, 18% of the stool donor’s bacterial amplicon sequence variants (ASVs) engrafted in the FMT recipient, with certain bacterial taxa like Bacteroides spp., Fusobacterium spp., and Lachnoclostridium spp. engrafting more frequently than others. Lastly, analyses indicated that the degree of overlap between the donor bacteria and the community of microbes already established in the FMT recipient likely impacts engraftment. Collectively, our work provides further insight into the microbiome and engraftment dynamics of dogs before and after taking oral FMTs.
... Enteropathies can be reversed in dogs with a change in diet, administration of antibiotics, or immunosuppressants (5). Among dogs' most used antibiotics for treating enteropathies are metronidazole, amoxicillin, tylosin, and lincomycin (6)(7)(8). The use of antibiotics can improve the clinical symptoms of patients with gastrointestinal infections; however, they cause negative alterations in the intestinal microbiota, and there is also concern about the selection of bacteria resistant to antibiotics (9). ...
Background
This study aimed to characterize potential probiotic strains for use in dogs to prevent infectious enteropathies. Lactic acid bacteria (LAB) isolated from canine milk and colostrum were characterized according to their functional properties, including their resistance to gastrointestinal conditions, inhibitory effect against pathogens, and intestinal adhesion.
Methods
The immunomodulatory effects of the strains were also analyzed in in vitro and in vivo studies. Among the strains evaluated, two LAB strains (TUCO-16 and TUCO-17) showed remarkable resistance to pH 3.0, bile salts, and pancreatin, as well as inhibitory effects against pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens.
Results
The TUCO-16 and TUCO-17 strains induced a significant increase in the expression of TNF-α, IL-8, and TLR2 in canine macrophages. The oral administration of TUCO-16 and TUCO-17 strains to mice significantly augmented their resistance to pathogenic E. coli or Salmonella intestinal infections. Both canine strains reduced intestinal damage and pathogen counts in the liver and spleen and avoided their dissemination into the bloodstream. These protective effects were related to the ability of TUCO-16 and TUCO-17 strains to differentially modulate the production of IFN-γ, IFN-β, TNF-α, IL-6, KC, MCP-1, and IL-10 in the intestinal mucosa.
Conclusion
Both strains, TUCO-16 and TUCO-17, are potential probiotic candidates for improving intestinal health in dogs, particularly for their ability to inhibit the growth of Gram-negative pathogens common in gastrointestinal infections and modulate the animal's immune response. Further studies are required to effectively demonstrate the beneficial effects of TUCO-16 and TUCO-17 strains in dogs.
... This therapy is often associated with diet and other drugs, leading to difficulties in interpreting the effectiveness of a single antimicrobial product. For example, studies have supported the efficacy of rifaximin and oxytetracycline or of metronidazole and tylosin with an additional anti-inflammatory action [9,[31][32][33]. If an antimicrobial treatment is not successful within two weeks, a new therapy should be considered, with the aim of achieving long-term control of the disease. ...
... A treatment plan with immunosuppressive drugs usually includes the use of these medications and modification of the diet [34]. Commonly used immunosuppressant drugs are azathioprine and cyclosporine [33,35]. ...
... They usually work together with other therapeutic approaches such as diet and antimicrobial agents. The most commonly used anti-inflammatory drugs are glucocorticoids, 5-aminosalicylates [33]. As reported before, there are a few antimicrobials with anti-inflammatory properties like metronidazole and tylosin [33]. ...
Chronic intestinal disorders (CID) are characterized by persistent, or recurrent gastrointestinal (GI) signs present for at least three weeks. In human medicine, inflammatory bowel disease (IBD) is a group of chronic GI diseases and includes Crohn’s disease (CD) and ulcerative colitis (UC). On the other hand, the general term chronic enteropathies (CE) is preferred in veterinary medicine. Different therapeutic approaches to these diseases are used in both humans and pets. This review is focused on the use of traditional therapies and nutraceuticals with specific antioxidant properties, for the treatment of CID in humans and animal patients. There is strong evidence of the antioxidant properties of the nutraceuticals included in this review, but few studies report their use for treating CID in humans and none in animals. Despite this fact, the majority of the nutraceuticals described in the present article could be considered as promising alternatives for the regular treatment of CID in human and veterinary medicine.
... 160 In a cohort of dogs with inflammatory bowel disease, administration of rifaximinhelped in significantly improving the clinical signs by either decreasing the pathogenic strains or by increasing the beneficial microbes. 161,162 Fecal Microbial Treatment, Bacterial Consortium Treatment and Phage Therapy Fecal microbial transplantation (FMT) is a process by which fecal bacteria is transplanted from a healthy donor to a diseased recipient's gastrointestinal tract. 3 Infusion of fecal microbiota exhibited clinical improvement in dysbiosis-associated diseases. ...
The human gut is a densely populated region comprising a diverse collection of microorganisms. The number, type and function of the diverse gut microbiota vary at different sites along the entire gastrointestinal tract. Gut microbes regulate signaling and metabolic pathways through microbial cross talks. Host and microbial interactions mutually contribute for intestinal homeostasis. Rapid shift or imbalance in the microbial community disrupts the equilibrium or homeostatic state leading to dysbiosis and causes many gastrointestinal diseases viz., Inflammatory Bowel Disease, Obesity, Type 2 diabetes, Metabolic endotoxemia, Parkinson’s disease and Fatty liver disease etc. Intestinal homeostasis has been confounded by factors that disturb the balance between eubiosis and dysbiosis. This review correlates the consequences of dysbiosis with the incidence of various diseases. Impact of microbiome and its metabolites on various organs such as liver, brain, kidney, large intestine, pancreas etc are discussed. Furthermore, the role of therapeutic approaches such as ingestion of nutraceuticals (probiotics, prebiotics and synbiotics), Fecal Microbial Treatment, Phage therapy and Bacterial consortium treatment in restoring the eubiotic state is elaborately reviewed.
... Therefore, rifaximin can have local effects in the gut after oral administration (12). In veterinary medicine, rifaximin is a good alternative to metronidazole for the treatment of the chronic enteropathy in dogs (13). Moreover, it is also used for the treatment of endometritis and mastitis in dairy cows (14,15). ...
Staphylococcus aureus (S. aureus) is a common pathogen that causes mastitis, an infection of the milk-secreting tissue of the udder, in dairy cows, and presents a huge economic problem for the dairy industry worldwide. Thus, control and treatment of mastitis in dairy cows is vital in order to reduce the costs associated with the disease. The main purpose of the current work was to examine the current dosage of rifaximin for the treatment mastitis in cows caused by S. aureus using pharmacokinetic/pharmacodynamic integration in a mouse mastitis model. The mouse mastitis model was established via injection of S. aureus Newbould 305 (400 CFU/gland) into the mouse mammary gland. A single dose of 50, 100, 200, or 400 μg/gland, administered via intramammary infusion, was used to study the pharmacokinetics of rifaximin. The pharmacokinetic parameters were analyzed by non-compartment and non-linear mixed-effect models using Phoenix software (version 8.1; Pharsight, USA). In vivo pharmacodynamics was used to examine 18 therapeutic regimens covering various doses ranging from 25 to 800 μg/gland and three dosing intervals of 8, 12, and 24 h per 24 h experiment cycle. The antibacterial effect of rifaximin was elevated with higher concentrations of rifaximin or shorter intervals of administration. The percentage of time that drug concentrations exceeded the MIC during a dose interval (%T > MIC) was generally 100% for rifaximin and was not better than AUC24/MIC in the sigmoid Emax model of inhibitory effect. The optimal antibacterial effect was 2log10CFU/gland when the magnitude of AUC24/MIC reached 14,281.63 h. A total of 14,281.63 h of AUC24/MIC was defined as a target value in the Monte Carlo simulation. The clinically recommended dosage regimen of 100 mg/gland every 8 h in 1 day achieved an 82.97% cure rate for the treatment of bovine mastitis caused by Staphylococcus aureus infection.
... No studies have evaluated a superior efficacy of antibiotics compared with other treatment modalities by means of randomized clinical trials (RCT), whereas one RCT comparing metronidazole 1 prednisolone versus prednisolone alone found no difference in short-term clinical remission [63,64]. ...
... Dogs affected by antibiotic responsive enteropathy (ARE) are generally young, predominantly belong to large breeds, and show remission of clinical signs following antimicrobial administration (metronidazole, tylosin, doxycycline, rifaximine) (8,9). It is thought that antimicrobials are able to modify the intestinal microbial population by counteracting its imbalances (i.e., dysbiosis); however, although a short-term response to metronidazole and tylosin has been reported, very few papers have described the long-term control of ARE (9)(10)(11). ...
The increasing incidence of gastrointestinal tract pathologies in dogs and the worrisome topic of antibiotic resistance have raised the need to look for new therapeutic frontiers. Of these, the use of probiotics represents a potential therapeutic alternative. Lactobacillus kefiri (Lk) is a species of Lactobacillus isolated from kefir. Previous studies have demonstrated that its administration in mice downregulates the expression of proinflammatory mediators and increases anti-inflammatory molecules in the gut immune system. It also regulates intestinal homeostasis, incrementing immunoglobulin A (IgA) secretion. Since Lk has never been studied as a single probiotic in dogs, the aim of this study was to evaluate the safety of Lk in dogs, and its effect on IgA secretion and on intestinal microbiota composition. Ten healthy dogs without a history of gastrointestinal diseases were included. The dogs received Lk at a dose of 10⁷ live microorganisms orally, once daily for 30 days. The fecal samples were tested before administration, in the middle, at the end, and 30 days after discontinuation. The IgA secretion concentration and the microbiota composition were evaluated on the fecal samples. The results in this study suggested that Lk did not influence the concentration of IgA, nor significant changes of the intestinal microbiota were observed during and after the treatment. Therefore, additional studies are needed to investigate if a higher daily dosage of Lk can influence the intestinal homeostasis of dogs.
... [34][35][36][37] Three studies report the outcome in dogs with ARE, and in 2 of these, remission or partial remission were achieved by all dogs. 5,36,38 However, most dogs treated with tylosin relapsed within a month when the antibiotic was discontinued. ...
In this article, the studies about the prevalence of chronic enteropathy are reviewed as well as the information regarding short- and long-term prognosis for dogs treated with the three most common therapies; these include dietary modification, antibiotics, and immunosuppressants. Although the data available are limited, most studies support a good to excellent long-term response in dogs that have a successful food trial, whereas the response is poor with antibiotics or on-going treatment is required to retain remission. There is a risk of antimicrobial resistance developing with inappropriate use of antimicrobials such as in these situations. The published information highlights the need for alternative strategies to antibiotic treatment to manipulate the GI microbiome, and in the final part of this article studies on the use of probiotic for the treatment of chronic enteropathy are reviewed.
... Another RCT compared the clinical efficacy of rifaximin (RIF) to metronidazole (MET) for treatment of dogs with CE. 24 All dogs enrolled in the study had chronic GI signs and histopathologic lesions of lymphocytic-plasmacytic intestinal inflammation suggestive of idio- pathic IBD. Twenty-four dogs were randomized to receive either RIF (n = 14 dogs) or MET (n = 10 dogs) for 21 days, with changes in disease activity (CIBDAI) and serum C-reactive protein (CRP) concen- trations measured at the end of the study period. ...
Background
The optimal medical treatment for chronic enteropathy (CE) in dogs and cats is controversial. Sequential treatment using diet, antimicrobials, and immunosuppressive drugs is the most common strategy used by clinicians.
Objectives
To review the evidence for the effectiveness of dietary, drug, and alternative health interventions for inducing clinical remission in dogs and cats with CE.
Animals
Retrospective study of dogs and cats with a diagnosis of chronic enteropathy.
Methods
MEDLINE and Centre for Agriculture and Bioscience International (CABI) databases (1950 to March 2017) were searched for randomized controlled trials (RCTs), observational studies, and case series. The primary outcome was induction of clinical remission. All studies were evaluated using the quality of evidence grading guidelines (I‐IV), which assign a score defining the strength and quality of the evidence.
Results
Twenty‐two studies (11 RCTs in dogs and 2 in cats and 9 cohort studies or case series) met the inclusion criteria for inducing remission of gastrointestinal (GI) signs. Of the 13 RCTs achieving grade I scores, 10 studies (totaling 218 dogs and 65 cats) compared single treatment: diet (n = 3), immunosuppressives (n = 3), antimicrobials (n = 2), anti‐inflammatory drugs (n = 1), and probiotics (n = 1). Three case series (grade III) reported clinical remission using an elimination diet fed to 55 cats and use of enrofloxacin to induce remission in dogs with granulomatous colitis (2 studies totaling 16 dogs).
Conclusions and Clinical Importance
The current evidence for treatment of CE is much greater in dogs than in cats. There is sufficient strong evidence to recommend the use of therapeutic GI diets, glucocorticoids, enrofloxacin, or some combination of these in dogs with CE. Therapeutic GI diets and glucocorticoids are most useful in cats with CE.
... 34 Metronidazole is commonly used in cases of IBD and secondary small intestinal bacterial overgrowth. Other antibacterial drugs such as oxytetracycline, tylosin 35 and, more recently, rifaximin 36 have been indicated for their use in IBD and they may be a better alternative to metronidazole. In addition, we have also found a high incidence of metronidazole toxicity in Labrador Retrievers and Labrador-crosses; however, metronidazole therapy was instituted to treat various pathologies (Table 1) and Labradors are also the most common breed in UK. 37 Therefore, the apparent breed predisposition should be viewed with caution. ...
Background
Metronidazole is an antibacterial, antiprotozoal and anthelmintic medication commonly used in veterinary medicine. We describe cases of neurotoxicity associated with the drug’s administration.
Methods
Medical records between 2004 and 2017 from four veterinary referral hospitals were reviewed. Inclusion criteria were the presence of neurological signs compatible with metronidazole toxicity, clinical history supporting recent metronidazole therapy and resolution of clinical signs upon discontinuation of metronidazole administration.
Results
A total of 26 dogs were identified with clinical signs supporting a diagnosis of metronidazole toxicity. Median age at presentation was 7.2 years (range, 0.1–12 years); median duration of treatment was 35 days (range, 5–180 days); median treatment dosage was 21 mg/kg BID (range, 13–56 mg/kg every 12 h); median resolution of the clinical signs upon discontinuation of metronidazole was 3 days (range, 1–26 days). Magnetic resonance imaging (MRI) of the brain was performed in 19 cases and only one dog had brain lesions affecting the dentate nuclei, which resembled the MRI appearance of this disease in humans.
Conclusions
We found evidence of neurotoxicity in dogs at much lower doses than previously reported and we suggest caution when administering metronidazole at doses > 40 mg/kg every 24 h, regardless of the duration of the treatment.
