Gut microbiota disorder caused by diterpenoids extracted from Euphorbia pekinensis aggravates intestinal mucosal damage.

Gut microbiota disorder caused by diterpenoids extracted from Euphorbia pekinensis aggravates intestinal mucosal damage.
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DOI:
10.1002/prp2.765
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发表时间:
2021-10
影响因子:
2.6
通讯作者:
Cao G
Cao G
中科院分区:
医学4区
文献类型:
--
作者:
Wang K;Xu X;Maimaiti A;Hao M;Sang X;Shan Q;Wu X;Cao G

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肠道菌群失调会导致肠道损伤。本研究评价了大戟总二萜类化合物(TDEP)长期给药后对肠道菌群和肠黏膜屏障的影响,并采用斯皮尔曼相关分析法分析肠道菌群与肠黏膜屏障的相关性。将小鼠随机分为对照组、TDEP(4、8、16 mg/kg)组、TDEP(16 mg/kg)+抗生素组。灌胃给药2周后,分别采用酶联免疫吸附试验(ELISA)和高效液相色谱法(HPLC)检测血清中的炎症因子(TNF-α、IL-6、IL-1β)和LPS以及粪便中的短链脂肪酸(SCFAs)。免疫印迹法检测结肠组织紧密连接(TJ)蛋白的表达。此外,通过16 SrDNA高通量测序研究了TDEP对小鼠肠道微生物群的影响。结果显示,TDEP可剂量依赖性地增加炎症因子的水平,降低TJ蛋白和SCFAs的表达,且TDEP组小鼠肠道菌群组成与对照组有显著差异。当添加抗生素时,肠道微生物群的多样性显著降低,结肠损伤更严重。最后,通过相关性分析,我们发现了9种可能与TDEP引起的结肠损伤有关的关键细菌(Barnesiella、Muribaculaceae_unclassified、Alloprevotella、Arthromitus_Arthromitus、Enterorhabdus、Alistipes、Bilophila、Mucispirillum、Ruminiclostridium)。TDEP引起的肠道菌群失调可能加重了结肠损伤,其机制可能与粪便中SCFAs含量减少、结肠组织TJ蛋白表达紊乱、炎症因子含量增加有关。从大戟根中提取并分离总二萜类化合物(TDEP),研究其对肠道菌群和肠黏膜屏障的影响。进行相关性分析以找出关键微生物群。结论:TDEP引起的肠道菌群失调可能加重了结肠损伤,其机制可能与粪便中SCFAs减少、结肠TJ蛋白表达紊乱、炎症因子含量增加有关。
Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long‐term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF‐α, IL‐6, IL‐1β) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme‐linked immunosorbent assay (ELISA) and high‐performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high‐throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose‐dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors. The total diterpenoids were extracted and isolated from the radix of Euphorbia pekinensis (TDEP), and it’s influence on gut microbiota and intestinal mucosal barrier were evaluated. Correlation analysis was conducted to find out key microbiota. In conclusion, we found the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.
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发表时间: 2017-03-01
期刊: American journal of physiology. Gastrointestinal and liver physiology
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