Mohn Lab uncovers gut microbiome differences in 3-month-old infants who go on to develop allergic disease

The inability of some infant microbiomes to perform carbohydrate metabolism may be a factor in the development of allergies later in life. Metagenomic analysis of the microbiomes of human infants who went on to develop allergies revealed a lack of genes encoding for carbohydrate breakdown and butyrate production, pointing to the potential importance of this pathway during early infancy in protecting against the later onset of allergies.

Allergic disease is a common, chronic health issue in children that currently lacks effective treatments and a firm understanding of its root causes. One area of investigation is the role of the gut microbiome in the etiology of these diseases and specifically microbially-derived short-chain fatty acids (SCFAs). SCFAs appear to affect the immune system and, in humans, are exclusively produced in the colon by bacterial fermentation. These colonic bacteria break down carbohydrates that human gut enzymes cannot and in doing so produce SCFAs such as butyrate.

In mice with altered gut microbiome and metabolite profiles that cause overactive immune responses and allergic-disease-like symptoms, supplementing with butyrate alleviates the exacerbated immune response and allergic symptoms while also compensating for the microbial dysbiosis. Now, a collaboration of Canadian researchers including Microbiome Insights co-founder Dr. William Mohn have produced evidence for a similar protective role of butyrate in human infants.

The group analyzed shotgun metagenomes of fecal samples from a case-control subgroup of children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based study following children from the prenatal period until age 5, collecting data on early life host and environmental factors that predict or cause allergic disease later in life. Results of the metagenomic investigation showed that the microbiomes of 3-month-old infants who later developed allergic disease had a decreased relative abundance of several bacterial taxa known for their involvement in butyrate production, and a deficiency in genes encoding the linked processes of carbohydrate degradation and butyrate production. There were also deficiencies in genes encoding for both butyrate fermentation and carbohydrate active enzymes responsible for degrading the main forms of indigestible carbohydrates in infants and young children: human milk oligosaccharides and plant cell walls.

This work adds more evidence to the idea that microbial dysbiosis during a critical window of development early in life increases the risk of developing allergic diseases like asthma. It also raises important questions like, what environmental factors drive the abundances of carbohydrate metabolism genes in the microbiome? Factors such as birth order, ethnicity, sex and exposure to farm animals are just a few of the known environmental factors associated with allergy risk, but this work was not designed to test their influence on the microbiome.

However, according to the authors, “the fact that we were able to identify a clear microbiome signature in a relatively small subset of the CHILD study suggests that there is a strong link between the metabolic potential of the microbiome and atopy development.” They also believe that the findings raise the possibility for two potential clinical interventions—the butyrate potential of the microbiome as a biomarker, and metabolite-based therapy for the prevention of allergic disease.

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