Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.
Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment.
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DOI：
10.3389/fphar.2020.620724
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发表时间：
2020
影响因子：
5.6
通讯作者：
Ji G
中科院分区：
文献类型：
--
作者：
Dai L;Tang Y;Zhou W;Dang Y;Sun Q;Tang Z;Zhu M;Ji G
美沙拉明已在临床上用于改善溃疡性结肠炎(UC)，但其潜在机制尚未得到很好的阐明。为了从肠道微生物区系和相关代谢产物的角度探讨美沙拉明的疗效，我们采用16S rRNA测序和代谢组学方法对14例正常对照组(NC组)、10例治疗初期UC患者(UC组)和14例美沙拉明治疗有效的UC患者(美沙拉明组)的粪便样本进行了检测。我们注意到UC组肠道微生物区系多样性和群落组成明显受到干扰，美沙拉明治疗后部分恢复。UC组192个属的相对丰度在属水平上发生显著变化，美沙拉明干预后168个属的相对丰度发生显著变化。同时，UC组共有127种代谢物发生显著变化，美沙拉明治疗后有129种代谢物发生显著变化。重要的是，我们观察到许多候选菌株被美沙拉明逆转，其中包括49个属(如志贺氏菌、肠球菌和丁酸杆菌)和102个代谢菌(如异亮氨酸、胆酸和脱氧胆酸)。Spearman相关分析表明，大多数候选物种与UC的Mayo评分显著相关，特定属的相对丰度与代谢产物的扰动显著相关。途径分析表明，这些属和候选代谢物富含许多相似的分子途径，如氨基酸代谢和次生代谢物的生物合成。重要的是，ROC曲线分析确定了肠道微生物区系特征，该特征由5个属组成，包括大肠杆菌-志贺氏菌、链球菌、巨型单胞菌、普雷沃特氏菌_9和[真细菌]_辅前列腺素_组，可用于区分UC组与NC组和美沙拉明组。综上所述，我们的结果提示美沙拉明可能通过不同途径的相关代谢产物调节肠道微生物区系特征而在UC中发挥有益的作用，这可能为开发新的UC候选生物标志物和治疗靶点提供基础。
Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [Eubacterium] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.
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影响因子：
9.4
作者：
Fite, Alemu;Macfarlane, Sandra;Macfarlane, George T.
通讯作者：
Macfarlane, George T.
影响因子：
30.3
作者：
Sinha SR;Haileselassie Y;Nguyen LP;Tropini C;Wang M;Becker LS;Sim D;Jarr K;Spear ET;Singh G;Namkoong H;Bittinger K;Fischbach MA;Sonnenburg JL;Habtezion A
通讯作者：
Habtezion A
影响因子：
5.4
作者：
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通讯作者：
Cogan, T. A.
影响因子：
4.6
作者：
Kojima, Ayuchi;Nakano, Kazuhiko;Wada, Koichiro;Takahashi, Hirokazu;Katayama, Kazufumi;Yoneda, Masato;Higurashi, Takuma;Nomura, Ryota;Hokamura, Kazuya;Muranaka, Yoshinori;Matsuhashi, Nobuyuki;Umemura, Kazuo;Kamisaki, Yoshinori;Nakajima, Atsushi;Ooshima, Takashi
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Ooshima, Takashi
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影响因子：
4.3
作者：
Shen ZH;Zhu CX;Quan YS;Yang ZY;Wu S;Luo WW;Tan B;Wang XY
通讯作者：
Wang XY