In a recent review published in the journal Nutrients, researchers in Italy investigated the influence of gut microbiota changes during the first 1000 days of life on the onset of food allergies (FAs) in children.
Background
Allergic diseases, encompassing conditions like asthma, FAs, and eczema, have seen a global uptick, especially in children. These diseases occur due to hypersensitivity reactions where the immune system abnormally responds to allergens. In the United States (U.S.), 1 in 13 children has FA, affecting their daily lives. Gut microbiota influences immune responses, with early microbial exposure benefiting immune development. The “hygiene hypothesis” posits that early infections protect against allergies, but sanitized lifestyles can disrupt this. While breastfeeding promotes healthy infant gut microbiota, factors like birth methods and antibiotic use can alter it. Studying these early-life microbiota changes can shed light on allergy onset, but further research is needed to pinpoint specific interventions for allergy prevention.
Review: The First 1000 Days of Life: How Changes in the Microbiota Can Influence Food Allergy Onset in Children. Image Credit: Christoph Burgstedt / Shutterstock
Methods for review
The narrative review was conducted based on literature from 2013–2023, sourcing from PubMed and Scopus databases. The authors focused on original papers, clinical trials, meta-analyses, and English-language reviews. Keywords utilized included ‘children,’ ‘gut microbiota,’ ‘breastfeeding’, ‘food allergy’, and more, while case reports and letters were omitted.
Understanding gut microbiota
“Microbiota” encompasses all microorganisms in a human body niche, mainly bacteria but also including viruses, fungi, and others. Gut microbiota, the most studied, is characterized by its richness, which refers to the total bacterial species, and diversity, indicating the number of individual bacteria per species. There is a differentiation between alpha diversity, which denotes single-sample complexity, and beta diversity, which describes taxonomic differences between samples. Atopy influences this gut diversity, and continual exposure to certain microbes can induce “inflammatory resilience.”
Epigenetics, diet, and allergies
Epigenetic changes, alterations in gene expression without changing deoxyribonucleic acid (DNA) sequences, play a role in allergic processes. Dietary habits influence microbiota composition by altering intestinal functions, gene expression, and the immune response. Microbiota-derived metabolites, such as Bifidobacteria and Lactobacilli, act as epigenetic substrates and influence DNA methylation. Dietary factors like pea proteins or saturated lipids can influence gut health, while breastfeeding might also impact DNA methylation, with some studies indicating associations with child DNA methylation patterns. Epigenetic changes linked with allergic diseases and affecting various immune cells underscore the need for more research into breastfeeding’s role in these epigenetic alterations and allergy prevention.
The significance of nutrigenetics
The digestion and metabolism of dietary molecules influence health through individual genotypes, known as nutrigenetics, and gene expression, termed nutritional epigenetics; the regulation of the latter by environmental and dietary factors is particularly relevant in FAs.
The first 1000 days: Gut microbiota and its significance
The first 1000 days after conception, which spans pregnancy, the newborn period, and the first two years of a child’s life, are vital for the establishment of a healthy gut microbiome. During this period, various factors can influence its composition; some, known as the “window of opportunity,” can be beneficial, whereas others, called the “window of susceptibility,” may increase disease risk. During this crucial time, interventions can potentially counteract the adverse effects of environmental risks, with factors such as vaginal delivery, breastfeeding, rural living, exposure to pets, and a fiber-rich diet emerging as protective against FA. Interestingly, a balance in the Enterobacteriaceae/Bacteroidaceae (E/B) ratio is essential for gut health, with deviations indicating an immature microbiome. Furthermore, short-chain fatty acids (SCFAs), especially butyrate, have protective roles against autoimmune and inflammatory diseases.
Gut health during pregnancy
Before birth, the maternal diet shapes a newborn’s gut microbiota, affecting allergy risks. Nutrients like vitamin D and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) are pivotal. Diets rich in vegetables and yogurt during pregnancy enhance offspring’s gut health, while certain foods increase allergy risks. Living on farms boosts children’s immunity through Treg cells.
Despite these findings, current guidelines from institutions like the American Academy of Pediatrics (AAP) do not recommend specific dietary restrictions for expecting mothers. Antibiotic use during pregnancy can influence the gut microbiota composition of offspring, potentially increasing allergy risk, while research suggests that a diversified diet fosters a varied microbiome, crucial for allergy prevention.
Gut microbiota in early infancy
During the sensitive phase of gut colonization in neonates, the neonatal gut begins with microorganisms sourced from the mother, including the placenta, vagina, and maternal gut. The mode of delivery, whether vaginal or C-section, significantly affects microbiota composition, with each favoring different bacterial families. Moreover, the location of delivery, such as home versus hospital, can impact the child’s health.
Allergies and gut microbiota
There is a significant link between gut microbiota and FA, with early infancy being critical for microbiota development. Variations in bacterial abundance and richness during the initial months can predict sensitization to specific foods later on. Additionally, antibiotic use in early life, which alters gut composition, is linked with allergy development.
Role of human milk microbiota
Contrary to old beliefs, human milk is not sterile but contains a wealth of microbes from the infant’s oral cavity and the maternal gut, playing a pivotal role in child health. Breast milk heavily influences the infant’s intestinal microbiota and can impact the potential development of food allergies.
Importance of human milk oligosaccharides (HMOs)
Human milk, the primary nutrition source for newborns, has garnered attention, particularly for the beneficial roles of HMOs. Not digested in the upper gut, these compounds act as food for specific beneficial bacteria, aiding infant development and potentially preventing allergies.
Gut microbiota during complementary feeding
Introducing solid foods to the infant diet increases microbial diversity in the gut, with the timing of introduction influencing both gut diversity and metabolism. However, it is essential to strike a balance. Delaying the introduction of allergenic foods is not recommended, as early exposure might actually prevent food allergies. Different feeding practices, like baby-led weaning, also influence gut microbiota and potential food sensitizations.
Microbiota Dysbiosis and FA
Dysbiosis and allergic response
Before FA onset, gut dysbiosis, which is an imbalance in microbial communities, is observed, and early disruptions in gut microbiota amplify allergic reactions by compromising the gut barrier. Food sensitization reduces gut microbial diversity with shifts in bacterial populations.
Factors affecting gut balance
Antibiotic use and high-fat diets risk dysbiosis by altering microbial diversity, with the latter promoting allergenic substances and changing bacterial counts. Maintaining a harmonious relationship between humans and their gut microbes prevents various pathological conditions.
Characteristics of FA-affected children’s microbiota
Children with FA exhibit reduced Bacteroides, Bifidobacteri, Clostridi, and increased Anaerobacter. Reduced bacterial diversity and butyrate-producing bacteria are observed, with gut microbiota composition differing between children who outgrow FA and those who persist with it. In the future, Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation may offer novel ways to manage gut microbiota, especially in predisposed children.