Spatially resolved architecture of the human gut microbiome and its health implications

The human gut microbiome shows dynamic variation throughout the lifespan and remarkable spatial organisation within the gastrointestinal tract. Complementing the focus of the first paper of this Series on the human microbiome dynamics and health, which focused on the temporal dynamics of the human gut microbiome, this second Series paper explores its biogeographical signatures, which often reflect distinct physiological niches in gastrointestinal tract regions. The spatial architecture of the gut microbiome is shaped by various factors and has important clinical implications for host homoeostasis, health, and disease. In this Series paper, we discuss current knowledge on the microbial biogeography along the gastrointestinal tract, the factors governing these spatial patterns, and their functional consequences for the host. We further focus on host-microbe interactions mediated by microbial metabolites and their impact on host health. Finally, we summarise the methodological advances that are enabling in-situ high-resolution spatial mapping of the gut microbiome as crucial tools for unravelling the detailed mechanisms of host-microbiome crosstalk. Overall, understanding the principles that govern the spatial ecology of the gut microbiome can inform the development of novel therapies designed to precisely manipulate microbial niches and restore homoeostasis along the gastrointestinal tract, thereby improving human health.