SAT041 18F-FDG PET/CT Mapping Of Functional Microbial Niches To Understand Host Glucose Regulation After BCG Vaccinations

Abstract

Abstract Disclosure: H. Dias: None. J.F. Fu: None. T.G. Luck: None. G.E. Wolfe: None. E. Hostetter: None. N.C. Ng: None. H. Zheng: None. W. Kühtreiber: None. J.C. Price: None. C. Catana: None. D.L. Faustman: None. Diverse microbiomes in humans are known to change host energy metabolism. When the bacillus Calmette-Guérin (BCG) vaccine, which consists of live but avirulent Mycobacterium bovis, is introduced as experimental therapy into human hosts with underlying type 1 diabetes (T1D), the BCG bacillus has been shown to gradually shift energy metabolism in host blood lymphoid cells from oxidative phosphorylation to aerobic glycolysis. Aerobic glycolysis draws more glucose out of the blood to fuel intracellular metabolism, and it may underlie the BCG bacillus’ therapeutic benefit: the systemic and long-term reduction of excess glucose from the blood of TID patients. The organ-specific niches where the BCG bacillus similarly alters metabolism and establishes persistent residence are not known. In a human clinical trial, we mapped the organ(s) niches for BCG-induced shift to aerobic glycolysis using fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and x-ray computed tomography (CT). This technique allowed us to reveal quantitatively, by Standardized Uptake Value Ratios, the organs with heightened glucose uptake in T1D participants (n=6) over a 2-year time-period after BCG vaccination versus before vaccination, as well as confirm earlier work that BCG vaccination gradually lowers blood sugar levels without any contribution from endogenous insulin. We also tested BALB/c mice (n=17) for the direct presence of BCG colonies in particular organ niches before and after vaccination. Results from both human and murine studies of the BCG microorganism concurred that the major anatomic site of functional metabolic change and residence is the spleen. The BCG bacillus also transiently mapped to the bone marrow, liver, circulating lymphocytes as in the descending aorta, and the lungs. Findings from human and murine studies support the spleen as the niche for the BCG vaccine’s functional improvement of metabolism. The spleen is significant because it is a lymphoid organ massive enough to explain BCG’s systemic benefit of lowering blood sugar to near normal levels in T1D. Presentation: Saturday, June 17, 2023