Towards a single integrated system of mucosal protection: the “common mucosal network”

This article extends a long history of study of the microbiome and immune protection of mucosal surfaces, with the aim of changing from a view that mucosal surfaces function as individual segments with limited connections to one of a single integrated network. This network is based on a continuous microbiome and a single immune apparatus driven by aggregated lymphoid structures embedded within the gut wall. The advantage of a single system is efficient communication and control, with powerful therapeutic implications. Regional variation within this system reflects different biological functions, with the respective microbiome and immune “couplets” adapting to those needs. The generation and expression of adaptive immunity within the lungs involves transfer of the microbiome from the airway by aspiration into the gut, and delivery of antigen-specific T cells from Peyer’s patches back to the respiratory mucosa, acting as a single system. Data from studies on different sections of the gut, on the female reproductive system, and on observations following COVID-19 infection support the idea of a single system. Oral supplements of inactivated respiratory bacteria enhance delivery of T cells to mucosal surfaces, reversing dysbiosis in those with chronic lung disease and preventing it in those exposed to risk. Recognition of this single “common mucosal network” provides new opportunities to therapeutically target mucosal dysbiosis, alone or in combination with direct manipulation of the dysbiotic microbiome.