Dissayabutra Thasinas, Chuaypen Natthaya, Somnark Pornjira, Boonkaew Bootsakorn, Udomkarnjananun Suwasin, Kittiskulnam Piyawan, Charoenchittang Pimpisa, Prombutara Pinidphon, Tangkijvanich Pisit
Metabolic Diseases in Gut and Urinary System Research Unit (MeDGURU), Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Chulalongkorn University, Bangkok, 10330, Thailand.
Sci Rep. 2025 May 3;15(1):15481. doi: 10.1038/s41598-025-00237-6.
The mechanistic role of gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) is increasingly recognized. Despite their close association, comparative data regarding gut dysbiosis in these disorders are limited. This study included 22 healthy controls and 180 patients (90 MASLD, 60 CKD, and 30 both diseases with sex- and age-matched). Fecal bacterial 16 S ribosomal RNA sequencing and butyryl-CoA: acetate CoA transferase (BCoAT) gene expression were analyzed. Plasma intestinal fatty acid binding protein (I-FABP), representing intestinal barrier dysfunction, was assessed using the ELISA method. Our data showed that alpha and beta diversities of gut microbiota differed between MASLD and healthy controls. However, only beta diversities were different between CKD and healthy individuals. The MASLD and CKD groups displayed fewer SCFA-producing genera, particularly Bifidobacterium, than healthy controls. Fecal BCoAT levels were inversely correlated with eGFR and I-FABP levels. Patients with CKD had significantly enriched pathogenic bacteria, reduced BCoAT, and increased I-FABP levels versus MASLD. Combining significant bacterial genera discriminated MASLD from CKD with high diagnostic accuracy (AUC of 0.90). Among patients with both diseases, gut microbial alterations showed mixed characteristics of MASLD and CKD. These data highlighted the shared and distinct gut dysbiosis and related biomarkers, which could provide a better understanding of MASLD and CKD pathogenesis.
肠道微生物群在代谢功能障碍相关脂肪性肝病（MASLD）和慢性肾脏病（CKD）中的机制作用日益受到认可。尽管它们密切相关，但关于这些疾病中肠道菌群失调的比较数据有限。本研究纳入了22名健康对照者和180例患者（90例MASLD、60例CKD以及30例同时患有这两种疾病的患者，均按性别和年龄匹配）。分析了粪便细菌16S核糖体RNA测序和丁酰辅酶A：乙酸辅酶A转移酶（BCoAT）基因表达。采用酶联免疫吸附测定法评估代表肠道屏障功能障碍的血浆肠脂肪酸结合蛋白（I-FABP）。我们的数据显示，MASLD与健康对照者之间肠道微生物群的α和β多样性存在差异。然而，CKD与健康个体之间仅β多样性不同。与健康对照者相比，MASLD和CKD组中产生短链脂肪酸的菌属较少，尤其是双歧杆菌属。粪便BCoAT水平与估算肾小球滤过率（eGFR）和I-FABP水平呈负相关。与MASLD患者相比，CKD患者的病原菌显著富集，BCoAT减少，I-FABP水平升高。结合显著的细菌属可将MASLD与CKD区分开来，诊断准确性较高（曲线下面积为0.90）。在同时患有这两种疾病的患者中，肠道微生物改变呈现出MASLD和CKD的混合特征。这些数据突出了共同和独特的肠道菌群失调及相关生物标志物，有助于更好地理解MASLD和CKD的发病机制。
