The road not taken: host genetics in shaping intergenerational microbiomes

The early-life gut microbiome is linked to human phenotypes as an imbalanced microbiome of this period is implicated in diseases throughout life. Several determinants of early-life gut microbiome are explored, however, mechanisms of acquisition, colonization, and stability of early-life gut microbiome and their interindividual variability remain elusive. Host genetics play a vital role to shape the gut microbiome and interact with it to modulate individual phenotypes in human studies and animal models. Given the microbial linkage between host generations, we discuss the current state of roles of host genetics in forming intergenerational microbiomes associated with mothers, offspring, and those vertically transmitted, providing a basis for taking into account host genetics in future early-life microbiome research. We further expand our discussion to the bidirectional interactions between host gene expression and microbiome in human health.