Coeliac disease risk not affected by early feeding practices

I'd like to bring three papers to your attention, all united by their discussion of coeliac (celiac) disease, that most classic of autoimmune conditions in the most part managed by the use of a lifelong gluten-free diet.

First up are the papers by Elena Lionetti and colleagues [1] and Sabine Vriezinga and colleagues [2] which unfortunately pour cold water on the notion that the risk of developing coeliac disease (CD) can be somehow mitigated via the use of either the early or delayed introduction of gluten nor seemingly affected by breastfeeding habits. Indeed, as science has known about for sometime, genes and specifically the HLA genotype linked to CD, seem to be the important predictors of disease outside of gluten consumption itself.

Both the Lionetti and Vriezinga papers were published in the New England Journal of Medicine and were accompanied by an editorial by Jonas Ludviggson among others (he of the 'not CD but something else potentially linking gluten and some autism'). Both studies were based on randomised controlled trials.

The Lionetti study involved either the introduction of gluten at 6 or 12 months to at-risk infants (those with a first-degree relative with CD) and then examining: "the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age". The numbers of participants involved featured in the hundreds so this was by no means an under-powered trial. The authors concluded that: "Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease".

The Vriezinga study looked at whether introducing gluten early (between 4-6 months) might also offset the risk of CD. Again based on a pretty impressive participant number (N=944) comprising children with a first-degree relative with CD as well as being "positive for HLA-DQ2 or HLA-DQ8", participants were randomly assigned to either "100 mg of immunologically active gluten daily" or a placebo. Again, biopsy confirmed CD and some of the various serology associated with CD were the outcomes. The authors concluded: "As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children".

The final paper to discuss today is that published by Elfström and colleagues [3] (open-access here) and the findings of their systematic review and meta-analysis looking at "associations between coeliac disease and type 1 diabetes". Type 1 diabetes, distinct from type 2 diabetes, is an autoimmune condition whereby the insulin producing cells of the body have been destroyed. The Elfström paper coincidentally carrying Dr Ludviggson as a co-author, concluded that: "More than one in twenty patients with type 1 diabetes have biopsy-verified coeliac disease" and onwards that there may be some substance to the idea that birds of an autoimmune feather flock together (see here). Indeed, I've previously covered the possibility of a connection between Type 1 diabetes and CD (see here) and how, for example, some of the research on [General] zonulin might be potentially very informative to this area (see here).

There's little more for me to say in this post aside from reiterating that when it comes to CD, genotype combined with gluten exposure seems to be the most important factors in disease onset and progression. That's not to say that a gluten-free diet might be the only tool in the management arsenal (see here) nor that other variables might not potentially impact on CD risk (see here) but for now, screening and where indicated, gluten avoidance, seem to be the primary measures to be undertaken.

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[1] Lionetti E. et al. Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. N Engl J Med. 2014 Oct 2;371(14):1295-1303.

[2] Vriezinga SL. et al. Randomized Feeding Intervention in Infants at High Risk for Celiac Disease. N Engl J Med. 2014 Oct 2;371(14):1304-1315.

[3] Elfström P. et al. Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes. Aliment Pharmacol Ther. 2014 Oct 1. doi: 10.1111/apt.12973.

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Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, Castellano E, Guariso G, Limongelli MG, Pellegrino S, Polloni C, Ughi C, Zuin G, Fasano A, Catassi C, & the SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk (2014). Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. The New England journal of medicine, 371 (14), 1295-1303 PMID: 25271602



Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, Kolaček S, Koletzko S, Korponay-Szabo IR, Mummert E, Polanco I, Putter H, Ribes-Koninckx C, Shamir R, Szajewska H, Werkstetter K, Greco L, Gyimesi J, Hartman C, Hogen Esch C, Hopman E, Ivarsson A, Koltai T, Koning F, Martinez-Ojinaga E, Te Marvelde C, Pavic A, Romanos J, Stoopman E, Villanacci V, Wijmenga C, Troncone R, & Mearin ML (2014). Randomized Feeding Intervention in Infants at High Risk for Celiac Disease. The New England journal of medicine, 371 (14), 1304-1315 PMID: 25271603



Elfström P, Sundström J, & Ludvigsson JF (2014). Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes. Alimentary pharmacology & therapeutics PMID: 25270960