The evidence is mounting that the dramatic increase in kids’ allergies over the past couple of decades could have something to do with medication-induced disturbances in the intestinal microbiome.
The latest evidence for this hypothesis comes from a large, retrospective US study published this week in JAMA, involving nearly 800,000 children under six months old. The researchers cross-checked the use of H2RA and PPI acid suppressants, as well as antibiotics, with the subsequent diagnosis of allergic diseases in this cohort.
Infants in the cohort who were prescribed acid suppressants were more than twice as likely to develop food allergies in later childhood, with peanut and cow’s milk allergies being the most common. They were also 70-80% more likely to develop an allergy to a medication, and 45-50% more likely to be hospitalised for anaphylaxis. Rates were also higher for allergic rhinitis and asthma.
Infants prescribed antibiotics also had higher allergy rates: they had double the risk of asthma, a 75% greater risk for allergic rhinitis and a 41% higher risk for anaphylaxis.
“Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit,” the researchers conclude.
They caution that as the study was observational, a causal link cannot be demonstrated. But while it is possible acid-suppressants or antibiotics were given for misdiagnosed allergic diseases, the authors say this is very unlikely to explain all the findings.
They say what is more likely is that acid-suppressants or antibiotics enhance the development of allergies by altering the makeup of the microbiome. They point to increasing evidence that healthy flora in the gut modulate immune responses and augment regulatory T-cell populations, possibly by the production of short-chain fatty acids. Getting the right microbial balance in early life seems especially important, with mouse studies showing antibiotic-induced dysbiosis causing allergies in neonatal mice but not in adult mice.
The study showed a stronger risk of food allergies with acid-suppressing drugs than with antibiotics, which might be because the former increases sensitisation to ingested antigens by decreasing protein breakdown in the stomach, the authors say. In addition, H2RAs may have a direct effect on the immune system, as histamine is increasingly recognised as having a role in modulating immune system function.
In current paediatric practice, acid suppressants are generally considered safe and are commonly prescribed for infants who have a regurgitation problem or are fussy. Studies like the current one may prompt a rethink in prescribing patterns, particularly given that gastric regurgitation in infants is not a disease but a developmentally normal process.
Recent research has found little clinical benefit in the use of H2RAs and PPIs in infants, and paediatricians are increasingly advising against overprescription of these drugs. They should be prescribed “only in situations of clear benefit”, the study authors warn.
You can access the full study here.