Early-life dog ownership may protect against development of Crohn’s disease
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SAN DIEGO — Dog ownership and close interactions with these pets in early childhood could help prevent later development of Crohn’s disease, according to data presented at Digestive Disease Week 2022.
“Our study seems to add to others that have explored the ‘hygiene hypothesis’ which suggests that the lack of exposure to microbes early in life may lead to lack of immune regulation toward environmental microbes,” Williams Turpin, PhD, research associate at Mount Sinai Hospital and the University of Toronto, said in a press release.
To determine whether environmental factors in different age groups affect the future risk for CD, Turpin and colleagues used an environmental risk assessment questionnaire to collect information from healthy first-degree relatives of patients with CD (n = 4,300) who were enrolled in the Genetic, Environmental and Microbial (GEM) project from Crohn’s and Colitis Canada.
The researchers examined questionnaire responses alongside historical data collected at the time of recruitment to assess for multiple environmental factors, including living on farms, consumption of unpasteurized milk and well water, family size, number of bathrooms in the home and pet ownership, specifically cats and dogs. They also analyzed approximate age at the time of each environmental exposure: aged younger than 1 year, 2 to 4 years and 5 to 15 years.
Turpin and colleagues used Cox proportional hazard models to identify exposures linked to future CD development, with regression models used in a secondary analysis to ascertain the relationship of exposures with biological factors previously associated with CD risk. These factors included intestinal permeability using urinary fractional excretion of lactulose to mannitol ratio (LMR; abnormal if 0.025), subclinical inflammation using fecal calprotectin (FCP) and fecal microbiome composition and diversity using 16S rDNA sequencing.
According to study results, living with a dog between the ages of 2 to 4 years (HR = 0.63; 95% CI, 0.44-0.99) and a large family size (>3 individuals) in the first year of life (HR = 0.36; 95% CI, 0.18-0.72) were associated with a lower risk for developing CD.
Although Turpin and colleagues found that family size in the first year was not linked to altered LMR, FCP or microbiome composition and diversity, dog ownership during the ages of 2 to 4 years (OR = 0.77, 95% CI, 0.60-0.93) significantly correlated with normal LMR. Researchers determined dog ownership at other ages consistently showed a significant association with normal LMR values, yet no link was found between dog ownership and FCP, microbiome composition and diversity.
“We did not see the same results with cats, though we are still trying to determine why,” Turpin said in the release. “It could potentially be because dog owners get outside more often with their pets or live in areas with more green space, which has been shown previously to protect against Crohn’s.”
Perspective
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An ultimate goal in inflammatory bowel disease care continues to be prevention of the diseases, as opposed to treating once they occur. As part of this effort, environmental studies continue to be important, intriguing and frustrating. Association with risk factor and the interaction with genetic susceptibility and mechanism continue to elude us.
The current study by Turpin and colleagues demonstrates this point. Eight environmental factors were assessed, and the study attempted to control to some extent genetic susceptibility by studying first-degree relatives of Crohn’s patients. Mechanism is explored by assessing intestinal permeability, microbiome characteristics and fecal calprotectin.
Understanding the impact of environment and harnessing this to improve patient outcomes continues to be challenging. The complex interaction between numerous environmental factors that may require a series of sequential events or exposures to result in the outcome, as opposed to one single event, makes detecting the actual risk factor difficult. In addition, the fact that the detected putative risk factor, such as dog ownership, may be a surrogate for the actual causative factor results in difficulty in clearly interpreting results.
Understanding why is also not always clear. For this study, the hygiene hypothesis is suggested that reduced exposure to pathogenic organisms during childhood leads to inappropriate immunological responses later in life. Seminal studies have shown exposure to microbes early in life alter immune function, and other studies have shown that dog ownership may contribute to a more diverse microbiome. Of note, this study did not detect a difference in diversity of microbiome between the two groups. It would be interesting to know whether the group with dogs experienced more childhood enteric infections.
This well-designed study is a welcome addition to our efforts to understand ways to protect against the development of IBD and is congratulated in that it includes assessment of mechanism in studies of microbiome and intestinal permeability. However, the question remains whether dog owners live in greener areas and eat fewer processed foods, are happier or are just more exposed to dirt or germs.
We look forward to more studies to understand how Crohn’s develops before we break out the prescription pad to order a trip to the animal shelter.
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Turpin W. Abstract 793. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego (hybrid meeting).
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