Poster Session 2 - E15
1,2Paige V. Bauer, 1Frank A. Duca, 1T. M. Zaved Waise, 1Helen J. Dranse, 1,2Brittany A. Rasmussen, 4Akshita Puri, 1Mozhgan Rasti, 2,4,5Catherine A. O’Brien, 1,2,3,6Tony K. T. Lam
1 Toronto General Research Institute and Department of Medicine, UHN, Toronto, ON; 2 Department of Physiology, University of Toronto, Toronto, ON; 3 Department of Medicine, University of Toronto, Toronto, ON; 4 Princess Margaret Cancer Centre, UHN, Toronto, ON; 5 Department of Pathobiology, University of Toronto, Toronto, ON; 6 Banting and Best Diabetes Centre, University of Toronto, Toronto, ON
Upper small intestinal lipid metabolism activates preabsorptive long chain acyl CoA synthetase (ACSL)-dependent pathways to regulate metabolic homeostasis, but whether diet-induced changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid preabsorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs preabsorptive fatty acid sensing and reduces the abundance of upper small intestinal Lactobacillus gasseri, as well as ACSL3 expression in the upper small intestinal mucosa. Transplantation of healthy upper small intestinal microbiota to high-fat fed rodents increases the abundance of Lactobacillus gasseri and restores the ability of upper small intestinal fatty acids to regulate glucose homeostasis via restoration of ACSL3 expression in the mucosa. Further, administration of Lactobacillus gasseri probiotics in non-transplanted high-fat fed rodents is sufficient to restore upper small intestinal ACSL3 expression and fatty acid sensing. In summary, we unveil a novel glucoregulatory role for upper small intestinal Lactobacillus gasseri that impacts an ACSL3-dependent glucoregulatory fatty acid sensing pathway.