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利用葡聚糖硫酸钠诱导的小鼠结肠炎模型,研究米诺环素、甲泼尼龙或联合治疗对结肠炎症状态下结肠细菌种群的影响。

Effect of minocycline, methyl prednisolone, or combination treatment on the colonic bacterial population in a state of colonic inflammation using the murine dextran sulfate sodium model.

机构信息

College of Pharmacy, Kuwait University, PO Box 24923, 13110, Safat, Kuwait.

出版信息

Microb Cell Fact. 2023 Nov 10;22(1):232. doi: 10.1186/s12934-023-02242-8.

DOI:10.1186/s12934-023-02242-8
PMID:37950185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10636938/
Abstract

BACKGROUND

Several reports demonstrated anti-inflammatory properties of minocycline in various inflammatory disorders including colitis. We have experimental evidence suggesting synergistic anti-inflammatory effect of minocycline with methyl prednisolone in reducing colitis severity in mice, but if this effect is in part related to modulating the composition of colonic microbiota is still unknown.

METHODS

the effect of vehicle (V), minocycline (M), methyl prednisolone (MP), or combination (C) regimen on the composition of the microbiota of mice in a state of colon inflammation compared to untreated (UT) healthy mice was determined using 16s metagenomic sequencing, and the taxonomic and functional profiles were summarized.

RESULTS

Overall, the bacterial flora from the phylum Firmicutes followed by Bacteroidota were found to be predominant in all the samples. However, the composition of Firmicutes was decreased relatively in all the treatment groups compared to UT group. A relatively higher percentage of Actinobacteriota was observed in the samples from the C group. At the genus level, Muribaculaceae, Bacteroides, Bifidobacterium, and Lactobacillus were found to be predominant in the samples treated with both drugs (C). Whereas "Lachnospiraceae NK4A136 group" and Helicobacter in the M group, and Helicobacter in the MP group were found to be predominant. But, in the UT group, Weissella and Staphylococcus were found to be predominant. Eubacterium siraeum group, Clostridia vadinBB60 group, Erysipelatoclostridium and Anaeroplasma genera were identified to have a significant (FDR p < 0.05) differential abundance in V compared to C and UT groups. While at the species level, the abundance of Helicobacter mastomyrinus, Massiliomicrobiota timonensis and uncultured Anaeroplasma were identified as significantly low in UT, C, and M compared to V group. Functional categories related to amino acid, carbohydrate, and energy metabolism, cell motility and cell cycle control were dominated overall across all the samples. Methane metabolism was identified as an enriched pathway. For the C group, "Colitis (decrease)" was among the significant (p = 1.81E-6) associations based on the host-intrinsic taxon set.

CONCLUSION

Combination regimen of minocycline plus methyl prednisolone produces a synergistic anti-inflammatory effect which is part related to alternation in the colonic microbiota composition.

摘要

背景

多项研究报告表明米诺环素具有抗炎作用,可用于多种炎症性疾病,包括结肠炎。我们的实验证据表明,米诺环素与甲基强的松龙联合使用可协同减轻小鼠结肠炎的严重程度,但这种协同作用是否部分与调节结肠微生物群的组成有关尚不清楚。

方法

采用 16s 宏基因组测序方法,比较了载剂(V)、米诺环素(M)、甲基强的松龙(MP)或联合(C)方案对处于炎症状态的小鼠肠道微生物群组成的影响,并对分类和功能谱进行了总结。

结果

总体而言,厚壁菌门和拟杆菌门的细菌菌群在所有样本中占主导地位。然而,与未治疗(UT)健康组相比,所有治疗组的厚壁菌门组成相对减少。在 C 组的样本中,发现放线菌门的比例相对较高。在属水平上,发现粘胶球形菌科、拟杆菌属、双歧杆菌属和乳酸杆菌属在两种药物(C)治疗的样本中占主导地位。而在 M 组中,普雷沃氏菌科 NK4A136 属和幽门螺杆菌属,在 MP 组中仅发现幽门螺杆菌属占优势。但是,在 UT 组中,发现韦荣球菌属和葡萄球菌属占优势。在 V 组与 C 组和 UT 组相比,发现真杆菌属 siraeum 组、梭菌属 vadinBB60 组、埃利希氏体属和厌氧原体属的丰度有显著差异(FDR p<0.05)。而在种水平上,发现幽门螺杆菌属 mastomyrinus、Massiliomicrobiota timonensis 和未培养的厌氧原体属的丰度在 UT、C 和 M 组中均显著低于 V 组。与氨基酸、碳水化合物和能量代谢、细胞运动和细胞周期控制相关的功能类别总体上在所有样本中占主导地位。鉴定出甲烷代谢是一种富集途径。对于 C 组,根据宿主固有分类群集,"结肠炎(减少)"是一个显著相关的(p=1.81E-6)关联。

结论

米诺环素联合甲基强的松龙的联合治疗方案产生协同抗炎作用,这部分与结肠微生物群组成的改变有关。

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