Evolution of infant gut microbiome and potential links to personalized health

Abstract

The human gut microbiome plays a critical role in health and disease. This complex community of microorganisms is established early in life and undergoes significant changes during infancy, a period crucial for long-term health. In infants, the gut microbiome is particularly dynamic, with the mode of delivery being one of the initial factors influencing its composition. Despite ongoing research, there are gaps in understanding the extent of maternal microbial transmission, the selection process of these microbes, and the factors influencing this selection. Specifically, it remains unclear how the gut microbiome, once acquired, differs in terms of evolutionary patterns in infants born via vaginal delivery or C-section. The current body of research lacks thorough investigation into specific microbial taxa present in the infant gut, that drive the evolution of gut microbes, particularly in association with delivery mode, neonatal health, and disease outcomes. One way to explore these microbial dynamics is through the study of HGT events, which can reveal how genetic material is exchanged between different microbial species in the gut. Using the WAAFLE tool, this study identified major drivers of HGT in infants born through either of the delivery modes. In CSD, there were 447 known HGT drivers, VD, there were 360. These include transfer of genes, like Salmonella enterica transfers the YagA gene to Klebsiella pneumoniae in CSD infants. Post-translational modifications were observed with a positive log2 fold change of 6 in this HGT driver. This gene is involved in PFAM integrase catalytic activity and regulates genes related to metabolism, with its transcription being affected by stress and conditions leading to biofilm formation. In VD infants, Butyricicoccus pullicaecorum transfers the lepB gene to 14 Bifidobacterium longum, which is involved in signal peptidase activity, a valuable target for antimicrobial drug development and this transfer exhibited a positive log2 fold change of 5 in intracellular trafficking, secretion, and transport. Additionally, Coprococcus catus transfers the alfA gene to Ruminococcus sp. 5_1_39BFAA in VD infants, a gene associated with the degradation and metabolism of HMOs. Ruminococcus sp_5_1_39BFAA is negatively associated with lactose, showing a coefficient value of -1.84e+00 and an FDR of 9.052e-05. Lachnospiraceae bacterium_2_1_46FAA and Ruminococcus gnavus HGT drivers are found in VD infants and are positively associated with NICU-admitted infants, with coefficient values of 1.15e+00 and 1.12e+00, respectively, and FDR values of 2.281e03 and 5.402e-03, respectively. The gene involved is xylB, which has antimicrobial properties and is involved in defense mechanisms. Notably, Coprococcus catus and Lachnospiraceae bacterium_2_1_46FAA were identified as a potential probiotic tailored to personalized health interventions.