At the right time in the right place: How do luminal gradients position the microbiota along the gut?

The gastrointestinal system is highly compartmentalized, where individual segments perform separate tasks to achieve common physiological goals. The gut luminal content, chyme, changes its chemical and physical properties as it passes through different intestinal segments. Together, the chyme composition, mucus, pH and oxygen gradients along the gut create a variety of highly distinct ecological niches that form, maintain and reinforce the symbiosis with the particular microbiota. Hosting different microbiota members at specific locations creates one of the most complex and sophisticated gradient – gradient of the local ecosystems that live and interact with each other, providing advantages and challenges to the host and creating our microbial self. Here, we discuss how intestinal luminal gradients are created and maintained in homeostasis, their role in a correct microbiota positioning, and their change upon inflammation and cancer. •The gastrointestinal system is highly compartmentalized.•Mucus, pH and Oxygen gradients are formed throughout the gut.•Intestinal luminal gradients create local ecological niches to foster symbiosis with particular microbiota.•Destruction of intestinal luminal gradients leads to mislocalization of microbiota members, inflammation and cancer.