Optimal antimicrobial response to a changing microbial background at a mucus interface

Complex lifeforms host microbiota, microbes that live synergistically with their host. Accordingly, hosts have mechanisms to defend against and tolerate the microbiota. The intestinal mucus, where these systems collide, plays a pivotal role in managing this relationship, yet lacks an integrative theoretical framework. We propose a minimal model to elucidate dynamics at this interface, focusing on the ileum’s mucus defense. The model considers the effect of delay in host antimicrobial peptide secretion and how the host can use two different signals, from the bulk microbiota and from segmented filamentous bacteria (SFB). Our theory suggests the host can optimize defense by minimizing antimicrobial peptide production and controlling bacterial exposure. Integrating two recent experiments, we show host dynamics are consistent with sensing both bulk and SFB, supporting our ‘optimal defense’ hypothesis. Therefore, we propose that similar mechanisms could prove advantageous to other species and applicable beyond the ileum’s mucus barrier.