GUT BACTERIA MODULATE T CELL RESPONSES AND ADVERSE CARDIAC REMODELING IN PRESSURE OVERLOAD INDUCED HEART FAILURE

Abstract

Changes in the bacterial composition of the gut, defined as gut dysbiosis, are recently becoming associated with the pathogenesis of heart failure (HF), a leading cause of mortality worldwide. Certain bacteria promote T cell activation, and T cell activation contributes to adverse cardiac remodeling and cardiac dysfunction in HF. We tested the hypothesis that gut dysbiosis modulates cardiac remodeling and function in a T cell‐dependent manner. C57/BL6 mice were orally treated with a wide spectrum antibiotic cocktail (ABX) and subjected to transverse aortic constriction (TAC), a stablished model of HF. ABX was present during the 4 week duration of TAC, thus sterilizing the gut completely, or during 3 weeks before TAC followed by removal during the 4 weeks of TAC duration to allow spontaneous reconstitution of the gut microbiota. We report that gut microbiota depletion results in reduced T cell activation in the mediastinal lymph nodes, heart T cell infiltration, and prevents cardiac fibrosis and cardiac hypertrophy in response to TAC. However, gut dysbiosis induced by bacterial reconstitution after ABX removal, only partially recovered this phenotype. We used 16S RNA sequencing to characterize the bacterial populations in Sham, TAC, and in ABX treated TAC mice after ABX removal and spontaneous bacterial colonization in the gut (TAC‐REC). TAC induced changes in the gut microbiota compared to Sham surgery, which at the genus level resulted in a higher relative abundance of Bacteroides (p=0.048) and lower relative abundance of Coprococcus (p=0.024), Lactobacillus (p=0.021) and Bifidobacterium (p=0.042), these last two normally associated to an anti‐inflammatory response. Bacterial reconstitution in TAC‐REC mice started after 2 weeks of ABX removal, but was incomplete even by 4 weeks post ABX removal, as reflected by the different relative bacterial abundance between TAC and TAC‐REC 4 weeks post TAC. Several genera were identified as colonizing the gut in TAC‐REC mice that could potentially be associated with cardiac dysfunction. Ongoing studies are focused on the characterization of bacterial populations responsible for this effect and on determining the type of T cell response involved.Support or Funding InformationThis work was supported by the NIH‐R01‐HL123658.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.