The etiopathogenesis for Crohn’s disease (CD) is still poorly understood. Most investigators feel that CD results from an inappropriate immune response to the microbiome in a genetically susceptible host. We know that “Westernization” is associated with CD; it has been postulated that a Western diet high in red meat and low in fruits and vegetables are to blame for the increasing incidence and prevalence of CD in developing countries. Others have theorized that processed food is the culprit. Other theories include the “hygiene hypothesis.” Essentially, decreasing infections through vaccinations and/or antibiotics may change the microbiome in a way that triggers the immune response leading to the development of CD. This hypothesis led some investigators to believe that “de-worming” ourselves is a possible etiology for the development of CD. Indeed, preliminary studies demonstrated that helminth therapy with a non-pathogenic pig whipworm, Trichuris suis, ameliorated IBD. However, a larger randomized, controlled trial demonstrated no therapeutic effect of helminth therapy.
At DDW 2022, Turpin and colleagues reported the results of a prospective cohort study that evaluated environmental risk factors for the development of CD in a cohort of healthy first-degree relatives (FDR). This study was part of the GEM project, a multinational, prospective cohort study of 5,122 FDR of patients with CD funded by the Crohn’s and Colitis Foundation of Canada. The study included 4,375 patients, of which 2.0% (86) developed CD. Participants completed an environmental exposure questionnaire to identify current and historical risk factors for CD, including living on a farm, drinking unpasteurized milk, water source from a well, family size, number of bathrooms, and living with household pets, including dogs and cats. Additionally, intestinal permeability was assessed using the lactulose to mannitol ratio, subclinical inflammation was examined by fecal calprotectin, and microbiome composition and diversity was assessed through 16 RNA sequencing.
Forty-seven percent of participants were male, the mean age at recruitment was 17.0 (range 6-25), and the median duration of follow-up was 5.6 years. They found that having a sibling with CD was associated with 1.6 odds of developing CD and that living with a bird increased the risk of development of CD nearly 3-fold (OR 2.83). Conversely, living in a household with more than three people in the first year of life, and living with a dog between the ages of two- to four-years, were associated with a reduced risk of development of CD (OR 0.41 and 0.61 respectively). Interestingly, FDR that lived in a household with a dog had normal intestinal permeability and had a more diverse microbiome. This was an exceptionally strong study, due to the prospective cohort design, large sample size, and thoughtful assessments; not surprisingly, it was highlighted in the Immunology, Microbiology, & Inflammatory Bowel Diseases Distinguished Abstract Plenary.
So, what are the take-home messages for providers, and how can you apply the science presented here to your clinical practice. First, many of our adult and pediatric patients (and parents) have concerns about their children and/or siblings developing CD. This study is reassuring, albeit with a little over five years of follow-up, as only 2.0% of FDR developed CD. Some unanswered questions exist though, in regards to environmental exposures. Why does exposure to a bird increase the risk for CD, whereas exposure to a dog decreases the risk? Since few participants had exposure to a bird, it is more useful to focus on exposure to a dog. Does this decrease the risk of CD through changes in the microbiome due to interactions with a dog? Is it related to improved mental health with alteration in the brain-gut axis? Or could it be related to more exercise-related to living with a dog? Prior studies have demonstrated the improvement of mental and physical health associated with dog ownership, including a 24% risk reduction in overall mortality and a 31% reduction in cardiovascular mortality.
As a gastroenterologist, should you recommend that a parent buy a dog? Pets, including dogs, are not a perfect fit for every family, which is consistent with the number of unwanted dogs in the U.S. According to the American Society for the Prevention of Cruelty to Animals, approximately 3 million dogs enter animal shelters yearly. So, there is an abundance of dogs in need of rescue in the U.S. So, for families that are open to dog ownership, a dog may indeed be a child’s best friend.
Dr. Cross has received grants from Janssen, and consulting fees from Abbvie, BMS, Eli Lilly, Fzata, Janssen, Magellan Health, Pfizer, Prometheus, Samsungbioepis, and Takeda.
Image by Jelena Jovanovic / EyeEm / GettyImages
