Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Inflamm Bowel Dis. 2024 Apr 3;30(4):529-537. doi: 10.1093/ibd/izad203.
Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.
By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).
Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.
We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.
原发性硬化性胆管炎（PSC）是一种慢性、纤维炎症性、胆汁淤积性肝病，其病因不明，常与炎症性肠病有关。最近的证据表明，肠道微生物群或其分子在 PSC 的发病机制中起着重要作用，与免疫和环境因素一起。
通过对 16S rRNA 和 ITS2 基因座的宏基因组测序，我们描述了 26 例患有 PSC 合并溃疡性结肠炎（PSC-UC）、27 例无 PSC 但有 UC（UC）和 26 例健康对照（CTRLs）的儿科患者的粪便微生物群和真菌群。
与 CTRL 相比，PSC-UC 和 UC 两组的细菌和真菌肠道失调明显；特别是，PSC-UC 中链球菌、酿酒酵母、Spirobolomyces、Tilletiopsis 和 Debaryomyces 增加，而 UC 中克雷伯氏菌、嗜血杆菌、肠球菌 Collinsella、Piptoporus、念珠菌和 Hyphodontia 增加。在两组患者中，阿克曼氏菌、拟杆菌、副拟杆菌、卵形螺旋体、Meyerozyma 和 Malassezia 减少。共现分析表明，与细菌相比，真菌网络的节点和边缘数量最少。最后，我们根据肝功能试验、细菌和真菌特征确定了一种特定的患者特征，能够将 PSC-UC 与 UC 患者区分开来。
我们描述了与 PSC-UC 疾病相关的肠道微生物群和真菌失调。我们的结果表明肠道失衡，具有抗炎特性的肠道共生微生物减少（即阿克曼氏菌、拟杆菌、副拟杆菌、卵形螺旋体、Meyerozyma 和 Malassezia），而病原体增加（即链球菌、酿酒酵母和 Debaryomyces），这可能与 PSC 的进展有关。总之，这些事件可能共同参与了 UC 框架下 PSC 的病理生理学。
