Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.
Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.
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菊粉补充剂可改善尿酸氧化酶（Uox）基因敲除小鼠的高尿酸血症，并调节其肠道微生物群。
DOI：
10.1007/s00394-020-02414-x
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发表时间：
2021-06
影响因子：
5
通讯作者：
Tian Z
中科院分区：
文献类型：
--
作者：
Guo Y;Yu Y;Li H;Ding X;Li X;Jing X;Chen J;Liu G;Lin Y;Jiang C;Liu Z;He Y;Li C;Tian Z
菊粉是一种可发酵的膳食纤维，不易消化，可通过调节肠道微生物群来改善代谢功能。本研究旨在通过敲除尿酸氧化酶（Uox）基因建立高尿酸血症小鼠模型，评价菊粉在高尿酸血症中的作用和肠道微生物群的微生物组成。KO（Uox敲除）和WT（野生型）小鼠通过管饲法给予菊粉或盐水7周。通过评估KO小鼠中血清UA（尿酸）水平、炎症参数、上皮屏障完整性、粪便微生物群改变和SCFA（短链脂肪酸）浓度的变化来确定菊粉对抗高尿酸血症的效果。补充菊粉可有效缓解KO小鼠高尿酸血症，增加小肠ABCG 2的表达，下调肝脏黄嘌呤氧化酶（XOD）的表达和活性。结果显示，KO组中的炎性细胞因子和LPS（脂多糖）的水平显著高于WT组，表明高尿酸血症小鼠的全身炎症，但菊粉治疗减轻了KO小鼠的炎症。此外，菊粉治疗修复了肠上皮屏障，如KO小鼠中肠TJ（紧密连接）蛋白[ZO-1（闭合小带-1）和闭合]水平增加所证明的。此外，尿毒症毒素，包括IS（硫酸吲哚酚）和PCS（对甲酚硫酸盐）的血清水平，降低菊糖处理的KO小鼠。进一步的研究揭示了菊粉补充增强了微生物多样性并提高了有益细菌的相对丰度，涉及SCFA产生细菌（例如，Akkermansia和Ruminococcus）。此外，菊粉治疗增加了KO小鼠中肠道微生物群来源的SCFA（乙酸盐、丙酸盐和丁酸盐浓度）的产生，这与高尿酸血症缓解的有效性正相关。我们的研究结果表明，菊糖可能是治疗高尿酸血症的一种有希望的候选治疗药物。此外，通过补充菊粉来缓解高尿酸血症至少部分地通过调节肠道微生物群及其代谢产物来调解。本文的在线版本（10.1007/s 00394 -020-02414-x）包含补充材料，可供授权用户使用。
Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites. The online version of this article (10.1007/s00394-020-02414-x) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
Guo Z;Zhang J;Wang Z;Ang KY;Huang S;Hou Q;Su X;Qiao J;Zheng Y;Wang L;Koh E;Danliang H;Xu J;Lee YK;Zhang H
通讯作者：
Zhang H
DOI：
10.1038/ismej.2015.53
发表时间：
2015-11
期刊：
The ISME journal
影响因子：
--
作者：
Maurice CF;Knowles SC;Ladau J;Pollard KS;Fenton A;Pedersen AB;Turnbaugh PJ
通讯作者：
Turnbaugh PJ
影响因子：
9.2
作者：
Fang C;Zhong H;Lin Y;Chen B;Han M;Ren H;Lu H;Luber JM;Xia M;Li W;Stein S;Xu X;Zhang W;Drmanac R;Wang J;Yang H;Hammarström L;Kostic AD;Kristiansen K;Li J
通讯作者：
Li J
影响因子：
24.5
作者：
Catry E;Bindels LB;Tailleux A;Lestavel S;Neyrinck AM;Goossens JF;Lobysheva I;Plovier H;Essaghir A;Demoulin JB;Bouzin C;Pachikian BD;Cani PD;Staels B;Dessy C;Delzenne NM
通讯作者：
Delzenne NM
影响因子：
29.4
作者：
Marchiando AM;Shen L;Graham WV;Edelblum KL;Duckworth CA;Guan Y;Montrose MH;Turner JR;Watson AJ
通讯作者：
Watson AJ