Popova Anna, Rācenis Kārlis, Brīvība Monta, Saksis Rihards, Saulīte Mikus, Šlisere Baiba, Berga-Švītiņa Egija, Oļeiņika Kristīne, Saulīte Anna Jana, Seilis Jānis, Kroiča Juta, Čerņevskis Harijs, Pētersons Aivars, Kloviņš Jānis, Lejnieks Aivars, Kuzema Viktorija
Department of Internal Diseases, Riga Stradins University, Riga, Latvia.
Center of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.
Sci Rep. 2025 Jul 31;15(1):28011. doi: 10.1038/s41598-025-13629-5.
Gut-associated lymphoid tissue is central to the production of galactose-deficient IgA1 (Gd-IgA1), a key factor in immunoglobulin A nephropathy (IgAN). Although no major differences in gut microbiome diversity have been reported across IgAN cohorts, functional alterations in microbial composition may contribute to disease pathogenesis. The study was designed as a cross-sectional study with an embedded prospective cohort component. Forty-eight adults with biopsy-confirmed IgAN-categorized as progressors (eGFR decline > 5 ml/min/1.73 m²/year, n = 23) or nonprogressors (n = 23)-and 23 healthy controls (HC) were recruited. Stool samples underwent metagenomic and functional profiling. Alpha diversity did not differ significantly between IgAN patients and HC. However, butyrate-producing bacteria (Butyrococcus, Agathobacter rectalis) were less abundant in IgAN patients. The sulfoquinovose degradation I pathway, associated with these bacteria, was also reduced. Nucleotide- and nucleoside-biosynthesis pathways were elevated in IgAN. Gd-IgA1 levels correlated with variations in metabolic pathways. Progressors demonstrated enhanced activity in isopropanol biosynthesis, biotin biosynthesis II, and phospholipid biosynthesis pathways. IgAN patients show reduced butyrate-producing bacteria and distinct functional changes in the gut microbiome suggestive of immune activation and inflammation. Progressors exhibit additional metabolic shifts linked to bacterial membrane stabilization.
肠道相关淋巴组织对于缺乏半乳糖的IgA1（Gd-IgA1）的产生至关重要，Gd-IgA1是免疫球蛋白A肾病（IgAN）的关键因素。尽管在IgAN队列中未报告肠道微生物群多样性的主要差异，但微生物组成的功能改变可能有助于疾病的发病机制。该研究设计为一项包含前瞻性队列成分的横断面研究。招募了48名经活检确诊的IgAN成人患者，分为病情进展者（估算肾小球滤过率下降>5 ml/min/1.73 m²/年，n = 23）或非进展者（n = 23），以及23名健康对照者（HC）。对粪便样本进行宏基因组和功能分析。IgAN患者和HC之间的α多样性无显著差异。然而，IgAN患者中产生丁酸盐的细菌（丁酸球菌、直肠阿加西杆菌）较少。与这些细菌相关的磺基喹诺糖降解I途径也减少。IgAN中核苷酸和核苷生物合成途径升高。Gd-IgA1水平与代谢途径的变化相关。病情进展者在异丙醇生物合成、生物素生物合成II和磷脂生物合成途径中表现出增强的活性。IgAN患者肠道微生物群中产生丁酸盐的细菌减少，且存在明显的功能变化，提示免疫激活和炎症。病情进展者表现出与细菌膜稳定相关的额外代谢变化。
