Patterned progression of bacterial populations in the premature infant gut

In the weeks after birth, the gut acquires a nascent microbiome, and starts its transition to bacterial population equilibrium. This early-in-life microbial population quite likely influences later-in-life host biology. However, we know little about the governance of community development: does the gut serve as a passive incubator where the first organisms randomly encountered gain entry and predominate, or is there an orderly progression of members joining the community of bacteria? We used fine interval enumeration of microbes in stools from multiple subjects to answer this question. We demonstrate via 16S rRNA gene pyrosequencing of 922 specimens from 58 subjects that the gut microbiota of premature infants residing in a tightly controlled microbial environment progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia, interrupted by abrupt population changes. As infants approach 33–36 wk postconceptional age (corresponding to the third to the twelfth weeks of life depending on gestational age at birth), the gut is well colonized by anaerobes. Antibiotics, vaginal vs. Caesarian birth, diet, and age of the infants when sampled influence the pace, but not the sequence, of progression. Our results suggest that in infants in a microbiologically constrained ecosphere of a neonatal intensive care unit, gut bacterial communities have an overall nonrandom assembly that is punctuated by microbial population abruptions. The possibility that the pace of this assembly depends more on host biology (chiefly gestational age at birth) than identifiable exogenous factors warrants further consideration.The vertebrate digestive system hosts a profound transition from a state of complete or near-sterility in utero to dense bacterial colonization within weeks of birth. This event has lasting effects on the host (1), influencing health and development (2–4), infection resistance (5, 6), predisposition to inflammatory (7) and metabolic disorders (8), and immune function (9), but remarkably little is known about this process. Gut colonization has been partly characterized in term infants (10–12) who reside in open venues, and who will, therefore, experience many exposures (e.g., contact with older children, adults, and pets, varying diets, oral antibiotics) that could drive microbial population assembly (1, 11–13).A delineation of the dynamics of the natural de novo assembly of this microbial community would form a basis for better understanding how the gut acquires its founding microbiome, and how the bacteria in the gut start their transition to population equilibrium (1, 14, 15). In view of the importance of bacterial gut colonization, we sought to determine if the initial assembly of host intestinal microbial populations follows discernible patterns, and if interventions such as antibiotics or nutrition alter this progression. A discernibly patterned progression would suggest that host biology influences bacterial community assembly more than do random encounters of individuals with microbes, whereas stochastic assembly would suggest that random encounters sculpt population structure. In this latter scenario, the gut serves as a passive culture chamber. Fine interval enumeration of gut contents from multiple subjects in as controlled an environment as possible is needed to answer this question.Here, we demonstrate that the gut microbiota of premature infants residing in a tightly controlled environment of a neonatal intensive care unit (NICU) progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia interrupted by abrupt population changes. The rate of assembly is slowest for the most premature of these infants.