Production of a Functional Factor, p40, by Lactobacillus rhamnosus GG Is Promoted by Intestinal Epithelial Cell-Secreted Extracellular Vesicles

Abstract

The symbiotic relationship between the gut microbiome and the host provides a nutrient-rich environment for gut microbes and has beneficial effects on host health. Although the composition of the gut microbiome is known to be influenced by both host genetics and environmental factors, host effects on the activities and functions of the gut microbial communities remain poorly understood. Intestinal epithelial cells exert front-line responses to gut microbes and contribute to maintaining a healthy intestinal homeostasis. Here, seeking to elucidate whether intestinal epithelial cells modulate Lactobacillus rhamnosus GG (LGG) functions, we examined the production of p40, an LGG-derived secretory protein that protects intestinal epithelial cells against inflammation. We found that growth medium conditioned with colonic epithelial cell-derived components promotes p40 protein synthesis and secretion by LGG and enhances LGG-stimulated protective responses in intestinal epithelial cells. Furthermore, when LGG was cultured with the colonic luminal contents from healthy mice, p40 production was upregulated but was attenuated with luminal contents from mice with intestinal inflammation. Importantly, the colonic epithelial cell-derived components potentiated LGG-produced p40 levels in a mouse model of colitis and enhanced LGG-mediated amelioration of intestinal inflammation in this model. Notably, we found that colonic epithelial cell-secreted extracellular vesicles participate in communicating with LGG and that heat shock protein 90 (HSP90) in these vesicles might mediate the promotion of p40 production. These results reveal a previously unrecognized mechanism by which the anti-inflammatory effect of LGG is reinforced by intestinal epithelial cells and thereby maintains intestinal health.

Antilisterial Potential of Lactic Acid Bacteria in Eliminating Listeria monocytogenes in Host and Ready-to-Eat Food Application

“…The subsequent activation of anti-apoptotic PI3K-downstream substrate, serine/threonine kinase (Akt/PKB), and inhibition of proapoptotic mitogen-activated protein kinase (p38/MAP) promote IECs' homeostasis. Hence, minimizing IECs' apoptosis and cytokine-induced apoptosis protects host cells from injury and inflammation [125,126]. TLR1 and TLR6 are indispensable for the activation of TLR2 signaling by forming heterodimers and are critical for GIT immune homeostasis maintenance.…”

Extracellular Vesicles: Recent Insights Into the Interaction Between Host and Pathogenic Bacteria

“…After infection, host-derived EVs (hEVs) demonstrate both antibacterial and probacterial effects under different conditions ( 7 , 34 , 35 ). On the one hand, the host could resist infection through hEVs in several ways.…”

“…Colonic epithelial cells released hEVs to Lactobacillus rhamnosus GG , which might mediate the production of p40. Consequently, Lactobacillus rhamnosus GG released p40 into the enteric cavity, protecting epithelial cells against inflammation ( 35 ).…”

Extracellular Vesicles in Teasing Apart Complex Plant-Microbiota Links: Implications for Microbiome-Based Biotechnology

“…EVs further facilitate beneficial communication between eukaryotic hosts and their microbiomes. For instance, colonic epithelial cell-derived vesicles facilitate the production of host-beneficial compounds by gut microbial communities ( 15 ). It is likely that mammalian mbEVs produced by gut flora microbes also distribute vital resources via body fluids to influence important host physiological functions ( 12 ).…”