Genetic, environmental and lifestyle factors influence the risk of food sensitization and food allergy in the first thousand days of life, according to a literature review published in Annals of Allergy, Asthma & Immunology.
Erin C Davis, PhD, Postdoctoral researchers in the Department of Allergy and Immunology of Pediatrics at the University of Rochester School of Medicine and Dentistry and the Center for Food Allergy at Golisano Children’s Hospital, University of Rochester Medical Center in Rochester, NY based their findings on a PubMed search following English language articles on food allergy (FA) and food sensitization (FS), prioritizing studies published after 2015.
The review examined the genetic risks of food allergy, associations between atopic dermatitis (AD) and food allergy, dietary allergen exposure in early life, maternal antigen consumption during pregnancy and lactation, breastfeeding and infant formula, introduction to solid foods, lifestyle and environmental exposures, the gut microbiome and metabolome in food allergy and potential early immune biomarkers of food allergy.
Genetic risks for food allergies include the number of parents or siblings with a history of allergic disease, although the researchers warn that part of this association may be due to family practice of avoiding the allergen for long periods of time or coming too late to introduce
In particular, researchers have found links between the major histocompatibility complex genes encoding the human leukocyte antigen complex and FA development, including sensitization to peanut, cow’s milk and egg.
The review also found that about one in three children with AD is susceptible to immediate-type IgE-mediated FA. One hypothesis suggests that the compromised skin barrier experienced by patients with AD allows for epicutaneous sensitization to food prior to oral ingestion.
Noting that infants can be exposed to allergens early in life, the researchers said the mechanisms behind sensitization or tolerance likely depend on how that exposure occurred.
For example, the researchers said, infants might be exposed to allergens in the womb or through breast milk or formula before eating solid foods. Environmental or household exposures to allergens are also plausible.
However, the researchers found sparse and conflicting results on the relationship between maternal allergenic food intake and infant FA risks, although key food allergens have been identified in amniotic fluid and breast milk. The American Academy of Pediatrics does not recommend maternal dietary restrictions for the prevention of atopic disease.
Studies that have evaluated the protective effect of breastfeeding against FA have been mixed, the researchers continued. Breast milk contains immunomodulatory components that shape the early life microbiome and immune system, but differences between women affect disease risk.
Introducing solid foods early appears to have a significant impact, as the researchers cited the Learning Early About Peanut study, which showed how early and sustained peanut intake might protect against peanut allergy. The Inquiring About Tolerance Study also found a 67% reduced risk of FA when introduced early in children ages 1 to 3 years.
The increasing adoption of a Westernized lifestyle that limits less industrialized exposures to microbial influences could contribute to increasing rates of FA and FS as part of the hygiene hypothesis, the researchers further found.
For example, larger families are associated with lower incidences of AD and hay fever. Exposure to pets and vaginal delivery are also associated with a lower risk of allergic disease. A farming lifestyle can also be protective.
Such early exposure to different populations of microorganisms can train the immune system to trigger tolerogenic responses during exposure to environmental or food allergens later in life, the researchers said.
The gut microbiome is now also a factor mediating the link between the increase in the prevalence of allergic diseases and industrialization. There may be a link between the development of FA and FS and less mature microbiomes, the researchers said, although studies have provided limited data.
Finally, the researchers found studies demonstrating associations between different infant immune profiles and FS and FA. The loss of immune cell populations and potential hyperresponsive profiles could increase the risk of aberrant responses, including sensitization, the researchers said.
Several factors drive the pathogenesis of the disease, including genetics, as well as maternal and infant allergen exposure, breast milk composition and other environmental factors, the researchers concluded, with tolerance or sensitization likely dependent on the route of initial exposure and possibly genetic risk.
In addition, the researchers called for additional observational and clinical trials spanning from early pregnancy through childhood to uncover new biomarkers and risk factors predicting susceptibility to FS and FA.