Abstract
A fundamental query in immunology is how cells recognize danger in the tissue milieu. For many years, standpoints were mainly centered around damaged cells or structures of invading pathogens, like lipopolysaccharide, being the initiators of danger signals to activate immunity. Today, rising evidence presents "biophysical signals" as potential regulators of immune cell functions too. This emerging notion of the ability of tissue mechanotransduction to tune the immunological system appears to likewise exist in other body system, among which is the metabolic system, where startling connection between mechanotransduction and enzymesknown to regulate metabolism have been also reported. Being continuously subjected to mechanical forces, and owing to its multifaceted role in not only absorbing and digesting nutrients, but also in supporting important immunological defense strategies as well as metabolic responses, attention has been lately given to organs making up the gastrointestinal (GI) tract, predominantly the intestine, with growing interest in unravelling the impact of mechanotransduction on the intestinal environment is on the rise. As such, we investigated in this study the impact of mechanical stress introduced by ingesting diet containing the indigestible fiber methylcellulose (MC) on gut immune and metabolic activities using the Drosophila melanogaster model organism. Our findings reveal that feeding on MC-containing diet causes consequential alterations in the fly gut environment manifested by enlargement of the midgut diameter, remodeling of the microbiota community, activation of immune responses, differential regulation of the tachykinin (Tk) peptide hormone expression and modulation of lipometabolism. Particularly, we show that feeding on MC-containing diet promotes a marked increase in the relative abundance of Leuconostocaceae/Leuconostoc, microbiota-dependent Reactive Oxygen Species (ROS) production, IMD pathway activation, and IMD-dependent elevation in Tk expression. We also demonstrate that maintaining flies on MC-containing diet for several days leads to a reduction in body weight and in systemic glucose and triacylglycerol levels and modulates lipid droplets accumulation and storage in the gut and fat body. Taken together, these findings provide novel insight into the effect of diet induced-mechanical forces on the intestinal physiology and pathology.
