Diaper Deposits Provide Insights Into the Early Human Microbiome

Before babies utter their first words, their microbiome is already telling a complex story – one that might hold key insights for cystic fibrosis, vaccine responses, and autoimmune diseases. In the early days of life, infants are exposed to a wide array of microbial influences that eventually build a community of commensal, or “healthy”, gut bacteria, which is as unique to each individual as their fingerprint. This process is highly dynamic and influenced by contributing factors such as the method of baby’s delivery (vaginal birth or cesarean section), the infants early nutrition (breastfeeding or formula feeding), and potential antibiotic exposure.  Early life exposures can shape the microbial community in ways that influence the developing immune system – a necessary step for newborns to acquire protection against infections or disease. One area of growing interest is how the development of the gut microbiome during infancy may be linked to bacteria-associated diseases like cystic fibrosis (CF), a genetic condition affecting the lungs and digestive system.

But what do the differences in each infant’s gut microbiota really mean for their health? Getting to the bottom of this question requires delving into deposits of data – quite literally – from the gut microbiome. In a recent study published in Gut Microbes by Dr. Jim Kublin from the Vaccine & Infectious Disease Division, researchers performed a comprehensive gene-level assessment of the microbiome on stool samples obtained from a mother-infant birth cohort over a period of up to six months after birth. With help from a genomic tool that identifies Co-Abundant Gene Groups (CAGs) developed in the Fred Hutch Data Core by the study’s lead author, Dr. Sam Minot, this team was able to identify almost 600 of the most abundant microbial organisms present in samples obtained from 15 infants over this critical early colonization period. “The development of the human microbiome during the earliest days of life is a highly dynamic process which has not been measured at consistent, dense intervals across previous studies,” states Kublin.

By integrating high-resolution genomic techniques and linear modeling with longitudinal sampling, Kublin, Minot and their colleagues provide an unprecedented view of microbial dynamics. “We found that in the earliest stages of human growth, individual species of gut bacteria do not grow in isolation but instead are observed growing in predictable groups – multi-species consortia. We provided genomic ‘coordinates’ for each of these consortia, which we hope others can use to better understand how this complex system develops,” explains Minot. These “consortiums”, or sets of bacterial species based on similarities in their gene expression, are groups of bacteria that exhibit highly correlated growth patterns, reflecting underlying biological interactions such as nutrient sharing or environmental co-dependence.

Temporally, variation in the composition of the infant microbiome peaked early, and as time passed the communities became more similar between samples and within consortia. In addition to effects observed with infant age, the authors were able to identify a multispecies microbial consortium, Consortium 9, which was less abundant in infants with CF compared to healthy controls. Levels of Consortium 9 microbes were also associated with infant weight (which is lower in infants with CF). Consortium 9 organisms included several species associated with CF, specifically Bacteroides, Paraprevotella, and Phocaeicola.

The discovery suggests a potential mechanistic link between the presence of these microbes and factors influencing weight gain in early life, which is an early symptom of CF. Similar to how Bifidobacteria cooperate to metabolize human milk oligosaccharides, the authors hypothesize that the beneficial effects of Consortium 9 arise from the collective activity of its members rather than any single bacterial species. Understanding the infant gut microbiome isn’t just about cataloging which bacteria are present – it’s more like decoding a symphony. Each species in a microbial consortium is like an instrument in an orchestra, contributing its unique notes to a harmonious performance. While identifying the individual instruments is important, the real insight lies in how they work together to create the symphony of health. By resolving microbial populations down to the sub-species level, the study provides a detailed view of the individual "instruments" and their roles in the microbial "symphony," uncovering nuances in microbial ecology that were previously obscured.

When speaking about the future applications for these tools, Minot emphasized the broader goals, stating, “Our primary interest is in how the gut microbiome influences the development of the human immune system, and vaccine response in particular. We hope to apply our findings to ongoing clinical trials to better design and deploy vaccines which robustly protect humans from infectious disease.” This research shows that when it comes to shaping early immunity, it really does take a microbial village.

Reference: Minot SS, Mayer-Blackwell K, Fiore-Gartland A, et al. Species- and subspecies-level characterization of health-associated bacterial consortia that colonize the human gut during infancy. Gut Microbes. 2024;16(1):2414975. doi: 10.1080/19490976.2024.2414975

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