Farm Exposures Influence Human Milk Composition and Might Reduce Allergies

Written by: Jyoti Madhusoodanan | Issue # 112 | 2023

Across the world, shifting from a traditional to an industrialized lifestyle changes the gut microbiome of adults. This same shift in lifestyle has also been correlated with an uptick in asthma and other allergies in children—conditions that are often preceded by changes in the gut microbiome. At present, food allergies affect approximately 1 in 13—or approximately 8 percent—of children in the U.S., according to the Centers for Disease Control and Prevention. But these conditions are rarer in children born to families that follow traditional farm-based lifestyles. For instance, fewer than 1 percent of children born in Old Order Mennonite (OOM) families are diagnosed with these conditions.

The farm-based lifestyles of OOM families benefit children, in part, because of their effects on mothers. Maternal exposure to microbes and to farm environments builds their immune response, which in turn protects children that are fed breast milk from allergies. One popular explanation for the effects of industrialization on immune health is termed the “hygiene hypothesis,” which proposes that being exposed to certain microbes in childhood helps the immune system mature.

Still, many gaps exist in researchers’ understanding of how the environment influences the gut microbiome and immune system. Early exposure to microbes and the development of the gut microbiome could all play a part in immune health of children [1]. To elucidate the many ways in which different environments might spur—or limit—the development of immune disorders and allergies, immunologist Kirsi Jarvinen-Seppo of the University of Rochester and her colleagues embarked on a multi-year project studying mothers and children in two environments that are geographically close but vastly different from one another.

The researchers recruited one group of participants from suburban and urban families in the Rochester, NY, area. The second group of participants were OOM families from the Finger Lakes region near Rochester. These communities live on single-family farms, have large families, and are in constant contact with pets and farm animals. They eschew cars and rely on horses and buggies for transportation. Babies are usually born at home rather than in hospitals and have minimal exposure to antibiotics. They are also breastfed for the first several months of life.

Gut microbiome differences

In a pilot study [2], the team compared the gut microbiome of infants born in Rochester and OOM families. They only included healthy babies who were born after 36 weeks of pregnancy and whose mothers did not have infections or known immune diseases. The researchers compared 65 OOM and 39 Rochester mother-baby pairs. They gathered stool samples from the age of 2 weeks to 6 months, as well as breast milk samples from the mothers.

By 2 months of age, differences between the gut microbiome of Rochester and OOM infants were evident. The latter had significantly higher levels of Bifidobacterium species, particularly B. infantis, a microbe that consumes complex sugary molecules known as human milk oligosaccharides (HMOs). Previously, researchers have found B. infantis levels in infant microbiomes higher in developing countries such as Gambia and Bangladesh, where autoimmune and allergic diseases are less frequent, and lower in Western countries where rates of these conditions are higher. The researchers detected B. infantis in 31 of 44 OOM infants but in only 5 of 24 Rochester babies.

When the researchers followed up with mothers via a phone call by the time children were three years old, they found 4 OOM children and 12 Rochester children had experienced signs of atopic disease, which includes eczema, asthma, food allergy, and hay fever. But “there was no significant association between atopic disease and presence of B. infantis,” they wrote in their paper [2].

Farming lifestyles and breastmilk

Breast milk is rich in HMOs, which feed specific microbial species in the infant gut microbiome. For example, they lead to the proliferation of various Bifidobacterium species. Previously, Jarvinen-Seppo and her colleagues found that the cocktail of HMOs in a mother’s milk can depend on her exposure to microbes. But whether a farming lifestyle—and the related microbial contact—could alter human milk composition was a mystery.

The researchers collected breast milk samples from mothers that had been lactating for about two months and measured the content of HMOs, antibodies, immune-modulating chemicals called cytokines, and fatty acids. They found strong correlations between maternal use of antibiotics and the proportions of different HMOs in milk [3]. When studying correlations with allergies, the team found that the kinds of antibodies present in breast milk differed based on the mothers’ lifestyles. For example, levels of antibodies against allergens from dust mites, egg, and peanut were significantly higher among OOM mothers compared with Rochester mothers. Atopic reactions were more common among children born to the urban families, and their occurrence was associated with breast milk that had lower levels of antibodies against dust mites.

The data suggest that maternal lifestyle and antibiotic use do influence the composition of breast milk [3]. This may have “downstream implications” for the development of a baby’s gut microbiome and immune system after birth, the authors wrote in their study [3]. But they add that larger, long-running studies are necessary to know whether the composition of breast milk in OOM families protects children from allergic disease.

Modified milk proteins

Approximately 70 percent of proteins in human milk bear sugary side chains critical to protein function. Although many studies have examined the roles of milk proteins, few have homed in on the variations in glycoproteins [4].

Continuing their analysis of breast milk, Jarvinen-Seppo and her colleagues analyzed glycoproteins present in 54 human milk samples from both the Rochester and OOM populations. In a 2022 study, they reported that differences in the sugar chains on proteins correlated with a mother’s lifestyle as well as whether they or their children suffered allergies. Using 20 Rochester and 34 OOM samples, the researchers found 38 glycoproteins in breast milk that were markedly different between the two groups, including immunoglobulin A1 [4].

But the researchers didn’t just stop at comparing samples based on differences in lifestyle alone. They also grouped the samples in two other ways. In one analysis, they compared samples from children with allergies against those from children without allergies. In another, they compared samples from mothers with or without allergies. Each time, distinct patterns emerged. But across all three studies, they discovered a set of three glycoproteins that were elevated in the OOM community, in mothers without allergies, and in children without allergies. Further studies are needed to understand the importance of these three glycoproteins, but they could affect immune development in infants and also hold clues to the origins of allergies.

References

1. Järvinen KM, Davis EC, Bevec E, Jackson CM, Pizzarello C, Catlin E, Klein M, Sunkara A, Diaz N, Miller J, Martina CA. Biomarkers of development of immunity and allergic diseases in farming and non-farming lifestyle infants: Design, methods and 1 year outcomes in the “Zooming in to Old Order Mennonites” birth cohort study. Frontiers in Pediatrics. 2022;10.
2. Seppo AE, Bu K, Jumabaeva M, Thakar J, Choudhury RA, Yonemitsu C, Bode L, Martina CA, Allen M, Tamburini S, Piras E. Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle. Allergy. 2021 Nov;76(11):3489-503.
3. Seppo AE, Choudhury R, Pizzarello C, Palli R, Fridy S, Rajani PS, Stern J, Martina C, Yonemitsu C, Bode L, Bu K. Traditional farming lifestyle in Old Order Mennonites modulates human milk composition. Frontiers in Immunology. 2021 Oct 11;12:741513.
4. Holm M, Saraswat M, Joenväärä S, Seppo A, Looney RJ, Tohmola T, Renkonen J, Renkonen R, Järvinen KM. Quantitative glycoproteomics of human milk and association with atopic disease. PLOS One. 2022 May 13;17(5):e0267967.

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