Bakker Guido J, Schnitzler Johan G, Bekkering Siroon, de Clercq Nicolien C, Koopen Annefleur M, Hartstra Annick V, Meessen Emma C E, Scheithauer Torsten P, Winkelmeijer Maaike, Dallinga-Thie Geesje M, Cani Patrice D, Kemper Elles Marleen, Soeters Maarten R, Kroon Jeffrey, Groen Albert K, van Raalte Daniël H, Herrema Hilde, Nieuwdorp Max
Department of Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands.
Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands.
Physiol Rep. 2019 Aug;7(16):e14199. doi: 10.14814/phy2.14199.
Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects. Ten lean and ten obese subjects with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Oral high-fat meal tests (50 g fat/m body surface area) were performed before and after vancomycin intervention. Gut microbiota composition, leukocyte counts, plasma lipopolysaccharides (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations and monocyte CCR2 and cytokine expression were determined before and after the high-fat meal. Oral vancomycin treatment resulted in profound changes in gut microbiota composition and significantly decreased bacterial diversity in both groups (phylogenetic diversity pre- versus post-intervention: lean, 56.9 ± 7.8 vs. 21.4 ± 6.6, P < 0.001; obese, 53.9 ± 7.8 vs. 21.0 ± 5.9, P < 0.001). After intervention, fasting plasma LPS significantly increased (lean, median [IQR] 0.81 [0.63-1.45] EU/mL vs. 2.23 [1.33-3.83] EU/mL, P = 0.017; obese, median [IQR] 0.76 [0.45-1.03] EU/mL vs. 1.44 [1.11-4.24], P = 0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by vancomycin in both groups. Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. 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 in this study.
摄入高脂餐会在餐后引发全身炎症反应，肥胖受试者的这种反应会增强。然而，这种反应的潜在机制尚未完全阐明。我们旨在评估肠道微生物群调节对瘦人和肥胖受试者餐后炎症反应的影响。十名患有代谢综合征的瘦人和十名肥胖受试者每天口服4次500毫克万古霉素，持续7天。在万古霉素干预前后进行口服高脂餐试验（50克脂肪/平方米体表面积）。在高脂餐前后测定肠道微生物群组成、白细胞计数、血浆脂多糖（LPS）、LPS结合蛋白（LBP）、IL-6和MCP-1浓度以及单核细胞CCR2和细胞因子表达。口服万古霉素治疗导致两组肠道微生物群组成发生深刻变化，细菌多样性显著降低（干预前后的系统发育多样性：瘦人，56.9±7.8对21.4±6.6，P<0.001；肥胖者，53.9±7.8对21.0±5.9，P<0.001）。干预后，空腹血浆LPS显著升高（瘦人，中位数[四分位间距]0.81[0.63-1.45]EU/mL对2.23[1.33-3.83]EU/mL，P=0.017；肥胖者，中位数[四分位间距]0.76[0.45-1.03]EU/mL对1.44[1.11-4.24]，P=0.014）。然而，两组中白细胞和血浆LPS的餐后升高不受万古霉素影响。此外，我们发现血浆LBP、IL-6和MCP-1或单核细胞CCR2表达没有变化。尽管万古霉素引起肠道微生物群的重大破坏并使空腹血浆LPS增加，但在本研究中，瘦人和肥胖受试者的餐后炎症表型未受影响。
