目的·观察大黄对大鼠肠道菌群与机体间的平衡关系的影响。方法·以Wistar大鼠为研究模型，将其随机分为4组（每组n=8），分别以大黄提取液0.1 g/kg（低剂量大黄组）、2.5 g/kg（中剂量大黄组）、4.5 g/kg（高剂量大黄组）及等量生理盐水（对照组）进行灌胃，连续给药5 d。每日观察大鼠粪便含水量的变化情况。采用气相色谱-飞行时间质谱（gas chromatography/time of flight mass spectrometry， GC/TOFMS）技术对第5日大鼠体内血清、结肠组织、粪便的代谢物进行检测，并采用主成分分析（principal component analysis，PCA）和偏最小二乘判别分析（partial least squares discrimination analysis，PLS-DA）方法分析不同剂量组与对照组间代谢物的差异，进一步采用t检验获得差异具有统计学意义的代谢物。结果·大黄给药后，大黄组大鼠粪便含水量随时间及剂量的增加逐渐增大。给药第5日，与对照组相比，不同剂量大黄组大鼠体内血清、结肠组织和粪便中分别检测到28、18和20种差异代谢物的水平有显著变化（P<0.05），且有17种血清代谢物、2种结肠组织代谢物、10种粪便代谢物的水平变化呈现剂量效应。其中，部分神经递质类物质、吲哚类物质、胆酸类物质等肠道菌群-宿主共代谢物给药后发生了显著变化。粪便中儿茶酚、吲哚-3-乙酸的水平明显升高，而苯丙氨酸、4-氨基丁酸、左旋多巴、吲哚-3-丙酸的水平明显降低；在高剂量大黄组结肠组织中脱氧胆酸明显升高；与对照组相比，不同剂量组中血清苯丙氨酸、酪氨酸、色氨酸的水平明显升高。此外，富马酸（能量代谢相关的有机酸类物质）在大黄给药后的粪便中明显下调，而在结肠组织和血清中明显上调。随着给药剂量增大，谷氨酸（氨基酸类物质之一）水平在血清中明显递增，但在粪便中逐渐递减。除了6-磷酸葡萄糖酸外，果糖、丙酮酸、乳酸、葡萄糖-1-磷酸、D-甘油-1-磷酸等糖代谢物和二十二酸、13-二十二碳烯酸、单硬脂酸甘油酯、胆固醇等脂代谢物的水平在血清中升高，而结肠组织中D-甘油-1-磷酸和粪便中乳酸、葡萄糖-1-磷酸、亚麻酸明显降低。结论·大黄通过肠道菌群-宿主共代谢作用影响了脑-肠轴、胆汁酸代谢，进一步作用于机体的能量代谢、氨基酸代谢、糖代谢和脂代谢。

Objective ·To study the effect of rhubarb administration on the balance between intestinal flora and the body. Methods ·Wistar rats were randomly divided into 4 groups (n=8), which were given extractions of rhubarb 0.1 g/kg (low dose group), 2.5 g/kg (medium dose group), 4.5 g/kg (high dose group) and normal saline (control group) by intragastric administration for 5 d, and the daily change of fecal water content of rats was observed. Gas chromatography/time of flight mass spectrometry (GC/TOFMS) approach was used to detect the metabolites in serum, colon tissue and fecal of rats on the 5th day of administration. Principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) were used to analyze the differences of metabolites between different dose groups and the control group. The metabolites with statistical significance were obtained by t-test. Results ·The water content of rat feces in the dose group gradually increased with the time and dose after rhubarb administration. Compared with the control group, 28, 18 and 20 differential metabolites were obtained in serum, colon tissue and fecal samples from different dose groups, which showed significant changes (P<0.05) on the 5th day. At the same time, the levels of 17 serum metabolites, 2 colon tissue metabolites, and 10 fecal metabolites altered significantly in a dose-dependent manner. Among these differential metabolites, some gut microbial-host co-metabolites, including neurotransmitters, indoles, and bile acids, were observed to alter significantly after rhubarb administration. The levels of fecal catechol and indole-3-acetic acid increased while the levels of fecal phenylalanine, 4-aminobutyric acid, L-DOPA, and indole-3-propionic acid decreased. Deoxycholic acid level was significantly elevated in colon tissue samples from the high-dose group. Compared with the control group, phenylalanine, tyrosine, and tryptophan levels in serum samples also increased in different dose groups. In addition, the levels of fumaric acid (one of organic acids related to energy metabolism), was down-regulated in fecal samples but up-regulated in colon tissue and serum samples. With the increase of dosage, the level of glutamic acid (one of amino acids) significantly increased in serum samples but gradually decreased in colon tissue samples. Except for 6-phosphogluconic acid, the levels of carbohydrates and lipid metabolites, including fructose, pyruvate, lactic acid, glucose-1-phosphate, D-glycero-1-phosphate docosenic acid, 13-docosenoic acid, 1-monostearoylglycerol, and cholesterol increased in the serum samples, while those of D-glycero-1-phosphate in colon tissue and lactic acid, glucose-1-phosphate, and linolenic acid in fecal samples decreased. Conclusion ·Rhubarb affects brain-gut axis and bile acid metabolism through the gut microbial-host co-metabolism, and further affects the body's energy metabolism, amino acid metabolism, glycometabolism and lipid metabolism.