Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.
Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.
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DOI：
10.5056/jnm22182
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发表时间：
2023-10-30
影响因子：
3.4
通讯作者：
Duan L
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang C;Zhang T;Zhang L;Duan L
肠易激综合征（IBS）被认为是一种肠-脑相互作用的疾病。黄连素和利福昔明是非吸收性抗生素，已被证实对IBS治疗有效，但仍缺乏直接比较它们的效果。本研究旨在比较两种药物对IBS患者肠道菌群引起的肠-脑轴改变的影响。无菌大鼠接受来自筛选的IBS患者和健康对照的粪便微生物群移植。在定植14天后，在接下来的14天内分别口服给予大鼠小檗碱、利福昔明或赋形剂。评价内脏敏感性，分析粪便微生物群并测定微生物短链脂肪酸。进行免疫荧光染色和形态学分析以评估小胶质细胞活化。小檗碱和利福昔明可减轻IBS-粪便菌群移植诱导的内脏高敏反应，小檗碱可增加蔗糖偏好率。两种药物均降低了微生物α多样性。与利福昔明相比，小檗碱显著改变了微生物结构，富集了毛梭菌。此外，黄连素而不是利福昔明显着增加粪便中的乙酸和丙酸浓度。小檗碱能恢复微生态失调引起的小胶质细胞形态学改变，这可能与其影响参与肽聚糖生物合成的微生物基因通路的表达有关。利福昔明既不影响活化的小胶质细胞的数量，也不影响小胶质细胞的形态学改变。小檗碱富集毛梭菌，降低肽聚糖生物合成基因的表达，增加乙酸和丙酸。利福昔明没有这些作用可以解释药物对微生物群-肠-脑轴的不同作用。
Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients. Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days’ colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation. Visceral hypersensitivity induced by IBS–fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations. Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.
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影响因子：
12.3
作者：
Ming J;Yu X;Xu X;Wang L;Ding C;Wang Z;Xie X;Li S;Yang W;Luo S;He Q;Du Y;Tian Z;Gao X;Ma K;Fang Y;Li C;Zhao J;Wang X;Ji Q
通讯作者：
Ji Q
影响因子：
3.6
作者：
Acosta A;Camilleri M;Shin A;Linker Nord S;O'Neill J;Gray AV;Lueke AJ;Donato LJ;Burton DD;Szarka LA;Zinsmeister AR;Golden PL;Fodor A
通讯作者：
Fodor A
影响因子：
9.3
作者：
Fang, Yuan;Zhang, Jindong;Duan, Liping
通讯作者：
Duan, Liping
影响因子：
158.5
作者：
Pimentel, Mark;Lembo, Anthony;Forbes, William P.
通讯作者：
Forbes, William P.
影响因子：
17.1
作者：
De Palma, Giada;Lynch, Michael D. J.;Bercik, Premysl
通讯作者：
Bercik, Premysl