Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria.

Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria.
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中药方(CoTOL)对接种肠道细菌的肥胖高尿酸血症小鼠血清尿酸和肠道菌群的影响

DOI:
10.1155/2020/8831937
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发表时间:
2020
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Lv H
Lv H
中科院分区:
其他
文献类型:
--
作者:
Gao Y;Sun J;Zhang Y;Shao T;Li H;Wang M;Zhang L;Bian H;Wen C;Xie Z;Lv H

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CoTOL是一种中医配方,临床上用于治疗痛风和高尿酸血症,特别是对反复发作的肥胖患者。然而,很少有研究研究CoTOL在降低尿酸的过程中如何影响肠道菌群。目前,我们分析了CoTOL成分的靶向细菌,并评价了CoTOL对接种黄嘌呤脱氢酶(XOD-)产生菌粪链球菌的肥胖性高尿酸血症小鼠尿酸和肠道菌群的影响。首先,从TCMID 2.0中检索CoTOL中的草药成分和这些成分的基因靶标,并通过David BioInformation Resources 6.8筛选这些基因,解密以检索细菌。然后,将3~4周龄雄性C57BL/6J小鼠随机分为6组,分别给予高脂饲料喂养8 周,达到肥胖标准。分别于第5、6、7周灌胃接种5 × 109CFU粪链球菌3次,第8周给予尿酸酶抑制剂草酸钾(PO,250 mg/kg)诱导高尿酸血症,1次/d,连续7d。模型第5周灌胃给予复方新诺明(0.4 ml/20g)和别嘌醇(40 mg/kg),1次/d,共4 周。分别于第4周和第8周采集粪便和血液标本。在不接种细菌的情况下,CoTOL组、别嘌醇组和空白组分别用CoTOL和别嘌醇或水处理。细菌44种(即粪肠球菌、链球菌等)以CoTOL中6种中草药的6种成分为靶点进行基因定位。接种粪链球菌显著提高了尿酸水平,改变了肠道菌群结构,而fi处理显著增加了阿克曼原虫的数量,减少了类杆菌和别杆菌的数量。此外,CoTOL在减轻体重方面显示了别嘌醇干预中没有观察到的独特效果。本研究首次证实CoTOL对高尿酸血症和超重有良好的治疗作用,其机制可能与调节物质代谢和改善肠道菌群结构或功能有关。因此,CoTOL可能是一种有希望的治疗高尿酸血症和超重的慢性痛风治疗方法,并可与传统治疗方法相结合。
CoTOL is a traditional Chinese medicine (TCM) formula in clinics for treating gout and hyperuricemia, especially in obese patients with recurrent attacks. However, fewer studies have investigated how CoTOL impacts the intestinal flora in reducing uric acid. In the present, we analyze the bacteria targeted by ingredients of CoTOL and evaluate the effects of CoTOL on uric acid and intestinal flora in a mice model of obese hyperuricemia inoculated with xanthine dehydrogenase- (XOD-) producing bacteria, Streptococcus faecalis. Firstly, ingredients of herbs in CoTOL and gene target by these ingredients were retrieved from TCMID 2.0, and these genes were screened by DAVID Bioinformatics Resources 6.8, deciphered to retrieve the bacteria. Then, 3-4-week-old male C57bl/6j mice were randomly divided into 6 groups and fed with high fat diet for 8 weeks up to obesity standard. The mice were inoculated intragastrically with 5 × 109 CFU Streptococcus faecalis 3 times at the 5th, 6th, and 7th week and intragastrically administrated with uricase inhibitor, potassium-oxonate (PO, 250 mg/kg), to induce hyperuricemia at the 8th week, once a day for 7 consecutive days, respectively (IB model). IB model plus CoTOL (0.4 ml/20g) and allopurinol (40 mg/kg) were administrated by gavage at the 5th week, once a day for 4 weeks. The feces and blood in each group were sampled at the 4th and 8th week. With no bacteria inoculation, CoTOL, allopurinol, and blank group were treated with CoTOL and allopurinol or water, respectively. 44 species of bacteria (i.e., Enterococcus faecalis, Streptococcus, etc.) genes were targeted by 6 ingredients of 6 herbs in CoTOL. Inoculation with Streptococcus faecalis significantly caused the elevation of uric acid and the change of intestinal flora structure, whereas treatment with CoTOL significantly increased the abundance of Akkermansia and those of Bacteroides and Alloprevotella decreased. Furthermore, CoTOL exhibited a unique effect on reducing weight unobserved in allopurinol intervention. The present study, for the first time, demonstrated that CoTOL has beneficial effects on hyperuricemia and overweight, which may be attributed to regulating material metabolism and improving the structure or function of intestinal flora. Thus, CoTOL may be a promising therapy for hyperuricemia and overweight in chronic gout management and can be integrated with conventional treatments.
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