Mapping the Healthy Infant Gut Microbiome Over the First Year
Background: Previous studies described the impact of various early life events on the developing gut environment of infants. Nevertheless, a comprehensive understanding of the time frame of the response of the healthy microbiome to specific factors, such as vaccination, introduction of solid foods etc., and the duration of these changes is currently lacking. Hence, determining the optimal sampling frequency needed to effectively monitor the complex development of the gut microbiome remains a challenge.  Methods: To address these gaps, we monitored the plasticity of the gut microbiome using 16S rRNA gene sequencing almost on a daily basis in one infant (infant A) and weekly in twelve other infants (B-M) during their first year of life. We associated these changes with external factors and monitored their length.  Results: With respect to the first occurrence and dynamics of changes in the abundance of bacterial genera in all infants, three dominant groups of bacteria emerged, comprising "Early-life colonizers", "Re-appearing colonizers" and "Later-colonizers". Related to the hypothesis that a weekly sampling may not be enough to capture changes in the microbiota composition accurately, we found that a range of individual samples analyzed within a week varied by more than 1 Shannon index value and coefficients of variation exceeded 10 % in 19 weeks. While alpha diversity indicators showed decreased variability with age, beta diversity variability remained high at the end of the first year. In particular, the introduction of solid food and probiotics led to gradual but significant changes in bacterial composition, with the duration and extent of the changes varying from infant to infant.  Conclusions: In our unique study, for the first time, we described in detail the mode of bacterial stages and colonizers in infants during the first year of life, finding that a similar colonization motif was observed regardless of sampling frequency.  We showed that sparse weekly sampling hindered a comprehensive understanding of how key factors - such as the maternal microbiome, probiotics, diet (breastfeeding vs. solid food), vaccinations, and unforeseen variables - affect the child's microbiome over time and in response to specific events early in life. Analysis of weekly and monthly variability in alpha and beta diversity suggests that such rare sampling may not be sufficient in terms of the outcomes of interest.