Bacteroidota and Lachnospiraceae Integration Into the Gut Microbiome at Key Time Points in Early Life are Critical for Neurodevelopment

Abstract

Background: The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Faecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements. Results: Preterm infants with suboptimal HCG trajectories had a depletion in the abundance/prevalence of Bacteroidota and Lachnospiraceae, independent of morbidity and caloric restriction. The severity of gut microbiome depletion matched the timing of significant HCG pattern separation between study groups at 30 weeks postmenstrual age. Consideration of the clinical variables indicated that optimal infant microbiome succession is primarily driven by dispersal limitation (i.e., delivery mode) and secondarily by habitat filtering (i.e., antibiotics and enteral feeding). Conclusions: Bacteroidota and Lachnospiraceae are known core taxa of the adult microbiome, with roles in dietary glycan foraging, beneficial metabolite production and immunity, and our work provides strong evidence that their integration into the gut microbiome needs to occur early for optimal neurodevelopment.

Metabolite profiling of human‐originated Lachnospiraceae at the strain level

“…According to an integrated analysis of 75 different studies on human gut metagenomic data sets, the Lachnospiraceae taxa accounted for approximately 10% of the total gut microbiomes [9]. In addition, Lachnospiraceae was detected in subjects of different age groups, including infants [10, 11], teenagers [12, 13], young and middle‐aged adults [14, 15], and elderly people [16–18]. The high prevalence and abundance, and lifelong associations with human beings suggest that Lachnospiraceae possibly plays important roles in human health and diseases throughout their lives.…”

The contribution of maternal oral, vaginal, and gut microbiota to the developing offspring gut

“…The copyright holder for this preprint this version posted December 19, 2022. ; https://doi.org/10.1101/2022.12.19.521059 doi: bioRxiv preprint solid foods in both humans and mice 13 , likely explaining the increase seen in this study. The decline in the proportion of Pseudomonadota and Bacillota as pups age may be due to the shift from an aerobic to an anaerobic environment within the intestines due to the decline in oxygen availability as pups age, causing a compositional shift favoring bacteria that are able to utilize anerobic respiration 25 .The maturation of the gut microbiota is further exemplified in these pups by the steady increase in fecal alpha diversity over time , as has been reported previously during early development in both species 4,5,26,27 .…”

A Digital Twin of the Infant Microbiome to Predict Neurodevelopmental Deficits

“…Our first data source comes from a cohort of ✺✽ preterm infants born less than ✸✺ weeks gestational age, recruited 9 from University of Chicago's Comer Children's Hospital to join the MIND (Microbiome in Neonatal Development) study (referred to as the UChicago cohort), which has developed a repository of microbiome samples with corresponding clinical, social, and environment data of preterm infants from birth to school age. This data cohort consists of longitudinal fecal samples of microbial abundances obtained from the subjects via 16S rRNA gene sequencing 19,20 measured weekly from birth to term-equivalent age for each patient (✷✹-✸✻ weeks PMA, See Extended Data Fig.…”

“…We consider two clinical phenotypes 9 : infants who ultimately attain appropriate (¿= -0.5 z-score difference) vs suboptimal (¡ -0.5 z-score difference) head circumference growth (AHCG, SHCG respectively). Overall patient characteristics are presented in Table 1.…”

“…Despite the availability of detailed -omics profiles on the constituent microbiome taxa, our understanding of the developing ecosystem in early life is relatively limited. While the role of the microbiome in brain development 7 , and the importance of microbial dysbiosis in neuroinflammation and neurodevelopmental disorders has been observed (including for preterm births 8 ), the underlying mechanistic pathways acting along the gut-brain axis remain unknown 9 .…”