A Network of Physiological Interactions Modulating GI Homeostasis: Probiotics, Inflammasome, mTOR

Abstract

The gastrointestinal surface is in constant interaction with various exogenous molecules. Exogenous components are discriminated in the GI context, as good, in case of nutrients and fibers, and bad, when they negatively affect host integrity. During this tolerogenic process, they also train the host's immune system. The immune system is a morphophysiologic unit driven by immune cells with the assistance of commensal organisms. Several species of commensal microorganisms have been used for centuries as probiotics due to their beneficial effects on human health. Lowering local levels of pro-inflammatory cytokines has a systemic effect, which is one of the fundamental characteristics associated with probiotics. Still, the primary mechanisms wiring those regulatory circuits as a unit remain unclear. Modulation of the innate immune system, via regulation of inflammasome assembly is emerging as a critical driver of this interaction. Stimulation of toll like receptors (TLR) and inner cell sensors like NLRP3 connect probiotics with essential host systems. In this context, the mTOR-regulated circuits, an intricate network modulating a cascade of protein phosphorylations, could be an important channel connecting host metabolism and probiotics crosstalk.

Interplays between inflammasomes and viruses, bacteria (pathogenic and probiotic), yeasts and parasites

“…Probiotic bacteria have no impact on inflammasome activation and pro-inflammatory cytokine synthesis in healthy individuals, but probiotics may regulate inflammasome activation in organisms that have previously experienced some degree of inflammation due to pathogenic bacterial infection [ 64 , 65 ].…”