Does intestinal inflammation alter the pathogenesis of E. coli Urinary Tract infections?
Urinary tract infections (UTIs) are a significant health concern for dogs, representing one out of every six veterinary visits. Among these cases, up to 25% develop recurrent UTIs, increasing the need for frequent veterinary care, extended antibiotic therapy, and added expenses for pet owners. The rise of multidrug-resistant UTIs has pushed researchers to explore the pathophysiology of UTIs more deeply and seek unconventional treatment methods.
UTIs in dogs are often caused by different strains of Escherichia coli (E. coli), each with varying pathogenic potentials. However, the specific conditions and mechanisms leading to strain-specific UTIs are not well understood. The gut microbiome is a critical factor linked to UTI pathogenesis and is considered the primary reservoir for uropathogenic E. coli. The connection between the gut and the bladder, known as the "gut-bladder axis," plays a pivotal role in understanding host-pathogen interactions in UTI development.
This trial aims to explore the differences in gut inflammation and permeability among healthy dogs, dogs with long-term gut problems (chronic enteropathy) , and dogs with urinary tract infections (UTIs). It also is looking at the possible connection between gut issues and the risk of bacteria moving to other parts of the body, focusing on E. coli. The trial will use both indirect and direct ways to measure gut permeability and will also look at the genes of bacteria found.
Dogs that are potentially eligible for this trial, will have a basic screening performed that includes questions about the dog’s history, a physical exam, blood work, a urinalysis and urine culture. Dogs will be enrolled into three different groups, healthy dogs, dogs with UTIs, and dogs with chronic enteropathy. If your dog is deemed to be eligible for enrollment into one of the groups, they will be scheduled for two trial visits (trial day 1 and day 3) with the Internal Medicine Service at the Veterinary Medical Center. Stool samples from your dog will be needed from 3 concurrent days (trial days 1-3) to be collected by the owner. On day 3, all dogs will stay a minimum of 8 hours at the Veterinary Medical Center to be tested for gut permeability. Dogs will have an intravenous (IV) catheter placed for blood collections, given an or medication called iohexol (a contrast agent commonly used in both veterinary and human medicine). Blood will be taken from the IV catheter over the next few hours, at designated timepoints, to be tested for the amount of iohexol that moves from the gut to the bloodstream.
Client Compensation:
For patients enrolled, the trial will cover a basic health screening (including a physical exam, CBC, serum biochemistry, urinalysis, urine culture, and fecal screening) on Day 1 and a follow-up visit on Day 3, and the testing for gut permeability. Owners are financially responsible for all veterinary costs associated with treatment of UTIs, inflammatory bowel disease, adverse events or injuries unrelated to trial procedures, and all costs unrelated to this trial (e.g. food, heartworm medications, medications for other conditions, etc.)
Potential Medical Benefits:
For dogs who qualify to enroll in this trial, the physical exam, bloodwork, urinalysis, urine culture, and gut permeability (iohexol) testing will be covered at no expense to you. Additionally, the information gathered in this study has the potential to help future patients by identifying risks associated with urinary tract infections and how we can better prevent and treat UTIs. Results of this study will not be available immediately. The goal is to develop new treatments and techniques that may help future patients. Study results may not be provided to you.
Potential Medical Risks:
While iohexol is not associated with adverse events, idiosyncratic adverse reactions may occur in a small subset of the canine population. Some dogs may experience an allergic reaction to the sedative or to iohexol, the medication used in this study to evaluate gut permeability. Other potential side effects of iohexol include diarrhea, nausea, and vomiting. Because of this, dogs will be routinely checked for adverse events during the iohexol administration and throughout their stay at the Veterinary Medical Center.
Diagnosis/Condition Being Studied: Urinary Tract Infections (UTIs)
Intervention to Be Studied: Gastrointestinal permeability
What qualifies my pet for enrollment?
Inclusion Criteria: Dogs with BCS of 3/9 – 7/9 and that weight more than 5kg (about 18-19lbs) are eligible for enrollment.
Exclusion Criteria: Dogs with the following are not eligible for enrollment.
All dogs:
• History of gastrointestinal (GI) disease or chronic skin disease.
• Being fed a raw diet
• Currently receiving probiotic supplements (external of food)
• Current intestinal parasitism
• A history of bladder stones
• Administered antibiotics in the past 30 days
• Currently receiving immunosuppressive therapy
• Diagnosis of anatomic abnormalities (e.g. hooded vulva) that predispose the dog to UTIs
| Healthy Dogs: | Dogs with urnary Tract Infection: | Dogs with Chronic Enteropathy: |
| • Abnormal physical exam findings indicative of GI disease, urinary tract disease, chronic skin disease, or other chronic illness • Abnormal findings on blood work (complete blood count and serum profile) • Evidence of a UTI, presence of lower UTI signs (LUTS) or recent increase in LUTS • Evidence of bacteriuria and/or pyuria on urinalysis • A positive urine culture | • Abnormal physical exam findings indicative of GI disease (excluding signs associated with a UTI), urinary tract disease, chronic skin disease, or other chronic illness (excluding findings associated with chronic enteropathy) • Abnormal findings on blood work (complete blood count and serum profile), excluding findings associated with a UTI | • Evidence of protein losing enteropathy • Abnormal physical exam findings indicative of GI disease, urinary tract disease, chronic skin disease, or other chronic illness (excluding physical exam findings associated with chronic enteropathy) • Abnormal findings on blood work (complete blood count and serum profile), excluding findings associated with chronic enteropathy |
PRE-SCREENING QUESTIONNAIRE
If you believe your pet may be eligible for this trial, please complete a pre-screening questionnaire.