J Allergy Clin Immunol
September 2025
Background: Disentangling preschool wheezing heterogeneity in terms of clinical traits, temporal patterns, and collective healthcare burden is critical for precise and effective interventions.
Objective: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.
Methods: Group-based trajectory analysis was performed in the CHILD Cohort study to identify distinct wheeze and allergic sensitization trajectories.
Proc Natl Acad Sci U S A
July 2025
The gut microbiota is highly dynamic during the first year of life and plays a crucial role in immune development. Breastfeeding is known to support infant health, but the contributions of the numerous breastmilk components to gut microbiota and immune maturation remain unclear. Secretory IgA (SIgA), the most abundant antibody in human milk, is a key modulator of gut microbiota composition.
View Article and Find Full Text PDFJ Allergy Clin Immunol
August 2025
Background: Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to interindividual variations in gut microbiota remain poorly understood.
Objective: We sought to integrate host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year of life.
Mucosal Immunol
February 2025
Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome.
View Article and Find Full Text PDFSocioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities.
View Article and Find Full Text PDFPLoS One
October 2024
Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP).
View Article and Find Full Text PDFMetagenomic sequencing has provided great advantages in the characterisation of microbiomes, but currently available analysis tools lack the ability to combine subspecies-level taxonomic resolution and accurate abundance estimation with functional profiling of assembled genomes. To define the microbiome and its associations with human health, improved tools are needed to enable comprehensive understanding of the microbial composition and elucidation of the phylogenetic and functional relationships between the microbes. Here, we present MAGinator, a freely available tool, tailored for profiling of shotgun metagenomics datasets.
View Article and Find Full Text PDFBackground: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
April 2024
Background: Early identification of children at risk of asthma can have significant clinical implications for effective intervention and treatment. This study aims to disentangle the relative timing and importance of early markers of asthma.
Methods: Using the CHILD Cohort Study, 132 variables measured in 1754 multi-ethnic children were included in the analysis for asthma prediction.
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e.
View Article and Find Full Text PDFGrowing evidence is demonstrating the connection between the microbiota gut-brain axis and neurodevelopment. Microbiota colonization occurs before the maturation of many neural systems and is linked to brain health. Because of this it has been hypothesized that the early microbiome interactions along the gut-brain axis evolved to promote advanced cognitive functions and behaviors.
View Article and Find Full Text PDFBackground: Early antibiotic exposure is linked to persistent disruption of the infant gut microbiome and subsequent elevated pediatric asthma risk. Breastfeeding acts as a primary modulator of the gut microbiome during early life, but its effect on asthma development has remained unclear.
Methods: We harnessed the CHILD cohort to interrogate the influence of breastfeeding on antibiotic-associated asthma risk in a subset of children (n = 2,521).
Secretory immunoglobulin A (SIgA) in human milk plays a central role in complex maternal-infant interactions that influence long-term health outcomes. Governed by genetics and maternal microbial exposure, human milk SIgA shapes both the microbiota and immune system of infants. Historically, SIgA-microbe interactions have been challenging to unravel due to their dynamic and personalized nature, particularly during early life.
View Article and Find Full Text PDFBackground/objective: The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity.
View Article and Find Full Text PDFFecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG).
View Article and Find Full Text PDFThe practice of rearing cows and calves together is gaining popularity on dairy farms, with different systems currently under assessment in mainland Europe, the United Kingdom, and Oceania. Research into the effects of cow-calf rearing has primarily focused on direct health and welfare implications, and little work has examined the role of different rearing paradigms on calf microbiota. We trialed a cow-calf rearing system on a Canadian dairy farm and compared fecal microbiota of these calves with the microbiota of calves reared according to the conventional practice of the same farm (separated from the dam and fed waste milk).
View Article and Find Full Text PDFMicrobiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify components of the neonatal gut niche that contribute to allergic sensitization. Our analysis reveals that newborns who develop immunoglobulin E (IgE)-mediated allergic sensitization (atopy) by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters are associated with both protection against atopy and the abundance of key taxa driving microbiota maturation.
View Article and Find Full Text PDFAlthough often neglected in gut microbiota studies, recent evidence suggests that imbalanced, or dysbiotic, gut mycobiota (fungal microbiota) communities in infancy coassociate with states of bacterial dysbiosis linked to inflammatory diseases such as asthma. In the present study, we (i) characterized the infant gut mycobiota at 3 months and 1 year of age in 343 infants from the CHILD Cohort Study, (ii) defined associations among gut mycobiota community composition and environmental factors for the development of inhalant allergic sensitization (atopy) at age 5 years, and (iii) built a predictive model for inhalant atopy status at age 5 years using these data. We show that in Canadian infants, fungal communities shift dramatically in composition over the first year of life.
View Article and Find Full Text PDFBacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD).
View Article and Find Full Text PDFIgA mediates microbial homeostasis at the intestinal mucosa. Within the gut, IgA acts in a context-dependent manner to both prevent and promote bacterial colonization and to influence bacterial gene expression, thus providing exquisite control of the microbiota. IgA-microbiota interactions are highly diverse across individuals and populations, yet the factors driving this variation remain poorly understood.
View Article and Find Full Text PDFPurpose Of Review: The microbiome and immune system are intrinsically linked, and during infancy these crucial biological systems undergo a concurrent and expansive maturation process. As these maturation processes progress, some children develop a sequence of IgE-mediated immune disorders termed the 'Allergic March', and unfortunately the prevalence of these lifelong and burdensome allergic conditions has increased over the past half century. Our current treatment strategies are unable to prevent or cure components of the Allergic March.
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