Inflammatory bowel disease and domestic hygiene in infancy
Abstract
To test the hypothesis that Crohn's disease is caused by delayed exposure to enteric infections, we did a case-control study. We compared 133 patients who have Crohn's disease and 231 with ulcerative colitis who have controls selected from the general population and matched for age and sex. Crohn's disease was more common in subjects whose first houses had a hot-water tap (odds ratio 5·0, 95% Cl 1·4–17·3) and separate bathroom (3·3, 1·3–8·3). Ulcerative colitis showed no clear relation to household amenities in infancy. These findings may explain why the incidence of Crohn's disease has increased in developed countries over the past 50 years.
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We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980.
Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2–2.5) and tobacco smoke (OR 1.5; 95% CI 1.2–1.9), and early life otitis media (OR 2.1; 95% CI 1.2–3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous.
Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies.
This study did not receive any funding.
BCG immunomodulation: From the ‘hygiene hypothesis’ to COVID-19
2021, ImmunobiologyThe century-old tuberculosis vaccine BCG has been the focus of renewed interest due to its well-documented ability to protect against various non-TB pathogens. Much of these broad spectrum protective effects are attributed to trained immunity, the epigenetic and metabolic reprogramming of innate immune cells. As BCG vaccine is safe, cheap, widely available, amendable to use as a recombinant vector, and immunogenic, it has immense potential for use as an immunotherapeutic agent for various conditions including autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infectious agents. Of particular interest is the use of BCG vaccination to counteract the increasing prevalence of autoimmune and allergic conditions in industrialized countries attributable to reduced infectious burden as described by the ‘hygiene hypothesis.’ Furthermore, BCG vaccination has been proposed as a potential therapy to mitigate spread and disease burden of COVID-19 as a bridge to development of a specific vaccine and recombinant BCG expression vectors may prove useful for the introduction of SARS-CoV-2 antigens (rBCG-SARS-CoV-2) to induce long-term immunity. Understanding the immunomodulatory effects of BCG vaccine in these disease contexts is therefore critical. To that end, we review here BCG-induced immunomodulation focusing specifically on BCG-induced trained immunity and how it relates to the ‘hygiene hypothesis’ and COVID-19.
Metagonimus miyatai ameliorates dextran sodium sulfate-induced colitis in mice
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Events Within the First Year of Life, but Not the Neonatal Period, Affect Risk for Later Development of Inflammatory Bowel Diseases
2019, GastroenterologyWe performed a population-based study to determine whether there was an increased risk of inflammatory bowel diseases (IBD) in persons with critical events at birth and within 1 year of age.
We collected data from the University of Manitoba IBD Epidemiology Database, which contains records on all Manitobans diagnosed with IBD from 1984 through 2010 and matched controls. From 1970 individuals’ records can be linked with those of their mothers, so we were able to identify siblings. All health care visits or hospitalizations during the neonatal and postnatal periods were available from 1970 through 2010. We collected data on infections, gastrointestinal illnesses, failure to thrive, and hospital readmission in the first year of life and sociodemographic factors at birth. From 1979, data were available on gestational age, Apgar score, neonatal admission to the intensive care unit, and birth weight. We compared incident rate of infections, gastrointestinal illnesses, and failure to thrive between IBD cases and matched controls as well as between IBD cases and siblings.
Data on 825 IBD cases and 5999 matched controls were available from 1979. Maternal diagnosis of IBD was the greatest risk factor for IBD in offspring (odds ratio [OR], 4.53; 95% confidence interval [CI], 3.08–6.67). When we assessed neonatal events, only being in the highest vs lowest socioeconomic quintile increased risk for later development of IBD (OR, 1.35; 95% CI, 1.01–1.79). For events within the first year of life, being in the highest socioeconomic quintile at birth and infections (OR, 1.39; 95% CI, 1.09–1.79) increased risk for developing IBD at any age. Infection in the first year of life was associated with diagnosis of IBD before age 10 years (OR, 3.06; 95% CI, 1.07–8.78) and before age 20 years (OR, 1.63; 95% CI, 1.18–2.24). Risk for IBD was not affected by gastrointestinal infections, gastrointestinal disease, or abdominal pain in the first year of life.
In a population-based study, we found infection within the first year of life to be associated with a diagnosis of IBD. This might be due to use of antibiotics or a physiologic defect at a critical age for gut microbiome development.