Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth

It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing), which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.
Author Summary Some obesity trajectories are set early in life, with rapid weight gain being a risk factor for later development of obesity. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. The existence of time-dependent exposure windows, which rely on stimuli from the gut to initiate healthy development, gives the evolution of early life gut microbiota a critical role in human health. We identified children that followed their expected growth trajectories at six months of life, and those that had deviated. We then developed a novel statistical approach that allowed the identification of longitudinal gut microbiota patterns (e.g. a particular species was detected at days 4, 10, and 30 and not detected at day 120) that were associated with expected growth, while appropriately restricting the false discovery rate. We further identified when a deviation from the proposed longitudinal gut microbiota patterns would result in an abnormal growth outcome (either rapid or decreased growth at six months of life). We found developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, as well as indications that Bacteroides species at day 30 was associated with growth.