北医三院段丽萍:小檗碱或可用于治疗IBS
创作:szx 审核:szx 02月18日
  • 小檗碱可显著缓解慢性避水应激诱导的大鼠内脏高敏感性,并降低结肠肥大细胞及脊髓小胶质细胞的活化;
  • 将小檗碱处理后的大鼠的粪菌移植给无菌大鼠,可在急性避水应激中起保护作用;
  • 移植IBS患者的粪菌可诱导大鼠的内脏高敏感性及小神经胶质细胞的促炎表型,小檗碱处理可抑制小神经胶质细胞的活化,并改变粪便菌群组成及短链脂肪酸谱;
  • 小檗碱无法直接抑制LPS诱导的小神经胶质细胞活化,而可能通过富集短链脂肪酸产生菌而发挥作用。
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szx
靶向肠道菌群失调的药物或可缓解IBS症状。来自北京大学第三医院的段丽萍团队在Acta Pharmacologica Sinica上发表的一项最新研究,发现小檗碱可通过调节肠道菌群组成,富集短链脂肪酸产生菌,从而在不同大鼠模型中抑制内脏高敏感性及小神经胶质细胞活化。
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Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation

小檗碱通过改变肠道菌群并抑制脊髓小神经胶质细胞激活以缓解大鼠的内脏高敏感性

10.1038/s41401-020-00601-4

02-08, Article

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Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg−1 ·d−1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota–gut–brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

First Authors:
Jin-dong Zhang

Correspondence Authors:
Liping Duan

All Authors:
Jin-dong Zhang,Jiao Liu,Shi-wei Zhu,Yuan Fang,Ben Wang,Qiong Jia,Hui-feng Hao,John Y Kao,Qi-hua He,Li-Jin Song,Fei Liu,Baoli Zhu,Chung Owyang,Liping Duan

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