Infants with siblings show greater gut microbiota maturity, lower odds for food allergy

Key takeaways:

• Higher microbiota-by-age z scores at age 12 months were associated with greater numbers of siblings.
• These higher scores also were associated with decreased odds for food allergy at age 12 months.

Mature gut microbiota at age 1 year mediated 63% of the protective effect of older siblings on risk for developing IgE-mediated food allergy in infancy, according to a study published in The Journal of Allergy and Clinical Immunology.

This effect appeared driven by the overall composition of the gut microbiota, not specific taxa, Yuan Gao, BSc, associate research fellow, Institute for Physical and Mental Health and Clinical Transformation, Deakin University, and colleagues wrote.

The study involved 323 infants (54.5% boys) randomly selected from the Barwon Infant Study cohort of 1,074 infants recruited in southeastern Australia between 2010 and 2013 with fecal 16S rRNA sequencing data at age 1, 6 and/or 12 months.

This group included 20 infants with clinically proven food allergy and 12 with polysensitization at age 1 year. The study also involved 60 infants (55% boys) with clinically proven food allergy, including 34 with polysensitization, at age 12 months for comparison with the random sample.

Patients had skin prick testing for cow’s milk, egg white, peanut, sesame, cashew, dust mite, cat allergen, dog allergen, ryegrass and Alternaria tenuis at age 1 year. Fecal samples were collected from mothers at 36 weeks of gestation and from infants at age 1, 6 and 12 months as well.

The group of 60 infants with clinically proven food allergy included three (5%) with a clinical history as well as an allergic reaction within 2 months of the 12-month review and a positive SPT result, classifying them as food allergic without food challenge.

The researchers also found that infants with food allergy or polysensitization had fewer older siblings and that they were less likely to live in a household with pets, particularly dogs.

The 20 most prevalent genera in the gut microbiota of these infants during the first year of age included Bifidobacterium and Escherichia/Shigella, which the researchers called highly abundant at age 1 month, reduced at age 6 months and further depleted at age 12 months.

Streptococcus, Veillonella, Lachnoclostridium and Lactobacillus were most prevalent in relative abundance at age 6 months. Also at 6 months, Faecalibaterium, Akkermansia and Roseburia became detectable before becoming increasingly more abundant at age 12 months.

Using amplicon sequence variants (ASVs), the researchers calculated the age of each microbiota. Higher microbiota-by-age z scores (MAZ) indicated greater maturity. The infants with food allergy had lower microbiota ages at age 12 months than the infants who did not have food allergy.

Risks for developing food allergy at age 12 months were associated with higher MAZ at age 12 months (OR = 0.45; 95% CI, 0.33-0.61) but not with MAZ at age 1 month or 6 months. None of the potential confounding factors altered estimates for MAZ at age 12 months by more than 10%.

Results were similar for polysensitization at age 12 months (OR = 0.44; 95% CI, 0.28-0.67). Adjustments for the age of the first introduction of eggs did not attenuate the association between MAZ and polysensitization at age 12 months (OR = 0.41; 95% CI, 0.26-0.64).

Additionally, there were no differences in abundances of the 25 most important ASVs in the model that predicted MAZ at age 12 months between infants with food allergy and those who did not have food allergy at age 12 months.

Higher MAZ was associated with a greater number of siblings (B = 0.15 per additional sibling; 95% CI, 0.05-0.24) and with having a dog in the home (B = 0.19; 95% CI, 0.02-0.35), both at age 12 months, as well as with having a cat in the home (B = 0.24; 95% CI, 0.03-0.44) at age 1 month.

There also was an association between less mature infant gut microbiota at age 1 month (B = –1.1; 95% CI, –1.54 to –0.67) and at age 6 months (B = –0.08; 95% CI, –0.12 to –0.05) and longer duration of breastfeeding.

Delayed maturation of the infant gut microbiota at age 6 months was associated with later introduction of solid food (B = –0.11; 95% CI, –0.2 to –0.03).

Using a log-odds scale, the researchers said that the total effect of a greater number of siblings on food allergy was –0.44 (95% CI, –0.83 to –0.06), with MAZ at 12 months mediating 63% of the protective effect these greater numbers have on food allergy.

The researchers similarly quantified the total effect of a dog in the home on food allergy as –1.02 (95% CI, –1.66 to –0.38), with MAZ at age 12 months mediating 27% of the protective effect these dogs have on food allergy.

Further, the researchers said there was an association between increased fecal concentrations of propionate at age 12 months and decreased food allergy. Levels of fecal propionate at age 12 months had a negative association with Turicibacter sanguinis (B = –1.93; 95% CI, –3.6 to –0.26) and a positive association with Escherichia/Shigella coli (B = 3.82; 95% CI, 0.24-7.4).

Based on these findings, the researchers concluded that there was an association between delayed maturation of the infant gut microbiota at age 12 months and increased risk for clinically proven IgE-mediated food allergy at age 12 months.

Also, the researchers continued, advanced maturation of the infant gut microbiota at age 12 months partly mediated the protective effect of older siblings on risks for developing an IgE-mediated food allergy.

Further insight into the underlying mechanisms of these associations, the researchers said, may inform strategies for preventing allergic disease in late infancy.