title: Crohn's disease and ruminant farming. Got lactase?
abstract: Crohn's disease (CD) is a well known chronic pathological condition whose aetiology has remained unrecognized for nearly a century. Complex immune mechanisms in a specific genetic background causing an abnormal local inflammatory response are thought to be directly responsible for the clinical picture, but no external factor triggering such host responses has been identified. Humans lose the capability of breaking down milk lactose early in life and, afterwards, ingestion of large amounts of lactose causes a transient digestive illness known as lactose intolerance. Some human populations developed mutations for lactase persistence in adulthood that allowed better exploiting a product, milk, from not food-competitive domesticated species. This adaptation to dairy farming could have had as a collateral effect the exposure of human populations to a ruminant parasite with the ability to cause chronic inflammation in the intestine. Humans with a genetic susceptibility might develop a similar inflammatory disease caused by a defect in a highly conserved innate immunity mechanism. Data from different published sources regarding by country CD and type I diabetes incidence, lactose intolerance, livestock population, food production, Gross National Income and human population were submitted to Pearson and Kendall correlation, multiple regression and principal components analyses. Multiple regressions were also applied to a published 20-year time series for CD incidence in Japan. These analyses showed a strong association between country incidence of CD and frequency of lactase persistence as well as other ruminant production and consumption variables that further supports the meaning of those observations. Association of these variables with higher per capita income suggests that IBD incidence would be a side-effect of an otherwise highly successful adaptation. The evolutionarily plausible framework provided by this association with the species suffering a similar inflammatory bowel disease (IBD), its coincidence with the expanse of a cattle breed that could act as a Trojan horse, in addition to recent microbiological, immunological and therapeutical observations consistent with a slow infection type of pathogenesis, supports a mycobacterial aetiology of human IBD. Further research challenging the hypothesis of a shared aetiology by Mycobacterium avium subsp. paratuberculosis of human and ruminant IBD by increasing research on the pathogenesis of the latter and focusing on effective specific antibiotic or immune aetiological therapies seems to be the obvious next step. Either confirmation or rejection of the hypothesis presented here should create new knowledge that will bring closer the eradication of a cause of human and animal suffering.
authors.affiliation: Department of Animal Health, NEIKER-Tecnalia, Berreaga, 1, 48160 Derio, Bizkaia, Spain. rjuste@neiker.net
authors.forename: Ramón A
authors.initials: RA
authors.lastname: Juste
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000201:enzymology / Q000209:etiology*; D003612:Dairying; D006801:Humans; D043322:Lactase / Q000378:metabolism*; D008962:Models, Theoretical; D012418:Ruminants
chemical_list: D043322:Lactase