Temporal changes in gastrointestinal fungi and the risk of autoimmunity during early childhood: the TEDDY study

Abstract

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over time, in contrast with the increase in bacterial diversity. Fungal profiles had high temporal variation, but there was less variation from month-to-month in an individual than among different children of the same age. Fungal composition varied with geography, diet, and the use of probiotics. Multiple Candida spp. were at higher relative abundance in children than adults, while Malassezia and certain food-associated fungi were lower in children. There were only subtle fungal differences associated with the subset of children that developed islet autoimmunity or type 1 diabetes. Having proper fungal exposures may be crucial for children to establish appropriate responses to fungi and limit the risk of infection: the data here suggests those gastrointestinal exposures are limited and variable.

Maturational patterns of the infant gut mycobiome are associated with early-life body mass index

“… 23 , 24 While descriptions of these early-life patterns are limited for gut fungi (collectively termed the gut mycobiome), there is evidence that fungi are also integrated in defined maturation patterns. 25 , 26 , 27 , 28 , 29 , 30 , 31 Infants are initially colonized by Candida , Malassezia , Cladosporium , and Saccharomyces and then exhibit communities abundant in Debaryomyces , Candida , Malassezia , and Cladosporium around 3 months of age. 25 , 27 , 28 , 30 , 31 , 32 , 33 , 34 From 1 year of age onward, the mycobiome shifts toward Saccharomyces dominance, alongside an increased presence of Rhodotorula .…”

“… 25 , 26 , 27 , 28 , 29 , 30 , 31 Infants are initially colonized by Candida , Malassezia , Cladosporium , and Saccharomyces and then exhibit communities abundant in Debaryomyces , Candida , Malassezia , and Cladosporium around 3 months of age. 25 , 27 , 28 , 30 , 31 , 32 , 33 , 34 From 1 year of age onward, the mycobiome shifts toward Saccharomyces dominance, alongside an increased presence of Rhodotorula . 25 , 27 , 28 , 29 , 31 These maturational patterns likely arise from an expanding variety of exposures over the course of early life, with a 3-month-old infant having greater exposure to skin microbes, such as Malassezia , through breastfeeding and frequent skin-to-skin contact with caregivers.…”

“… 25 , 27 , 28 , 30 , 31 , 32 , 33 , 34 From 1 year of age onward, the mycobiome shifts toward Saccharomyces dominance, alongside an increased presence of Rhodotorula . 25 , 27 , 28 , 29 , 31 These maturational patterns likely arise from an expanding variety of exposures over the course of early life, with a 3-month-old infant having greater exposure to skin microbes, such as Malassezia , through breastfeeding and frequent skin-to-skin contact with caregivers. 30 , 34 In contrast, with the introduction of solid foods and development of crawling behavior, infants are exposed to a greater number of fungi with food or environmental origins, such as Saccharomyces and Fomitopsis .…”

“… 30 , 34 In contrast, with the introduction of solid foods and development of crawling behavior, infants are exposed to a greater number of fungi with food or environmental origins, such as Saccharomyces and Fomitopsis . 27 , 30 From a diversity perspective, the patterns of mycobiome maturation are inconsistent across studies, with reports of increasing, 25 , 29 , 30 decreasing, 28 , 35 and unchanged or fluctuating 27 , 31 , 33 , 34 alpha diversity metrics over the course of early life. Similarly, differential associations between fungal beta diversity and infant age have also been reported.…”

“…Similarly, differential associations between fungal beta diversity and infant age have also been reported. 27 , 28 , 29 , 30 , 31 , 33 Beyond these patterns of infant gut mycobiome maturation, it is not well understood how host and environmental factors influence gut mycobiome establishment and how this may subsequently impact infant growth trajectories.…”