Effects of Vancomycin altered microbiota on postprandial inflammation

Objective Intake of a high-fat meal induces a systemic inflammatory response which is more severe in obese subject. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on the postprandial inflammatory response in lean and obese subjects. Design Ten lean and ten obese, metabolic syndrome subjects received oral vancomycin 500 mg four times a day for seven days. Oral fat load tests (50 g fat/m2 body surface area) were performed before and after intervention. Gut microbiota composition was determined by 16S sequencing. Leukocyte counts and plasma lipopolysaccharide (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations were determined at t=0, t=2h and t=4h after fat loads. Flow cytometry of monocyte CCR2 expression was performed at t=0 and t=4h after fat loads. Results Vancomycin treatment resulted in profound changes in gut microbiota composition. Moreover, fasting plasma LPS significantly increased after vancomycin intervention (lean, median (IQR) 0.81 (0.63-1.45) EU/mL to 2.23 (1.33-383) EU/mL, p=0.017; obese, median (IQR) 0.76 (0.45-1.03) EU/mL to 1.44 (1.11-4.24), p=0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by treatment in both groups (lean and obese group respectively: mean postprandial leukocyte count iAUC 1.70±1.20 and 2.73±1.90 10e9/L*h before and 2.35±1.75 and 2.33±1.32 10e9/L*h after treatment, mean LPS iAUC 0.76±0.97 and 1.17±1.39 EU/mL*h before and 5.19±8.33 and 2.13±5.24 EU/mL*h after treatment). Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. Conclusion Despite major vancomycin-induced disruption of the gut microbiota and increased fasting plasma LPS, the postprandial inflammatory phenotype in lean and obese subjects was unaffected. Further research is needed to disentangle the role of the gut microbiota in postprandial inflammation in humans.