Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA–microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.

肠道微生物组和 microRNA (miRNA) 在肝性脑病 (HE) 的发展中都发挥着作用。然而，粪便中微生物组和宿主来源的 miRNA 之间的功能联系仍然知之甚少。在本研究中，与慢性乙型肝炎患者相比，HE 患者的肠道微生物组和粪便 miRNA 发生了改变。将 HE 患者的粪便和粪便 miRNA 转移到受体小鼠体内会加重硫代乙酰胺诱导的 HE。hsa-miR-7704（一种在 HE 患者粪便中高度富集的宿主来源的 miRNA）口服灌胃后，会以微生物组依赖性方式加重小鼠的 HE。从机制上讲，hsa-miR-7704通过抑制proB来抑制长双歧杆菌的生长和粘附。B. longum及其代谢物乙酸盐通过抑制小胶质细胞活化和氨生成来减轻 HE。我们的研究结果揭示了 miRNA-微生物组轴在 HE 中的作用，并表明粪便 hsa-miR-7704 是 HE 进展的潜在调节因子。