Si Jiyeon, Lee Giljae, You Hyun Ju, Joo Sae Kyung, Lee Dong Hyeon, Ku Bon Jeong, Park Seoyeon, Kim Won, Ko GwangPyo
Medical Science Research Institute, School of Medicine, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
Comput Struct Biotechnol J. 2021 Oct 28;19:5920-5930. doi: 10.1016/j.csbj.2021.10.032. eCollection 2021.
Non-alcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus (T2D), and these two metabolic diseases demonstrate bidirectional influences. The identification of microbiome profiles that are specific to liver injury or impaired glucose metabolism may assist understanding of the role of the gut microbiota in the relationship between NAFLD and T2D. Here, we studied a biopsy-proven Asian NAFLD cohort (n = 329; 187 participants with NAFLD, 101 with NAFLD and T2D, and 41 with neither) and identified , , and as the principal taxa associated with the severity of NAFLD and T2D, whereas and were specific to NAFLD. In particular, the taxa that were associated with both severe liver pathology and T2D were also significantly associated with markers of diabetes, such as fasting blood glucose and Hb1Ac. Enterotype analysis demonstrated that participants with NAFLD had a significantly higher proportion of and a lower proportion of than a Korean healthy twin cohort (n = 756). However, T2D could not be clearly distinguished from NAFLD. Analysis of an independent T2D cohort (n = 185) permitted us to validate the T2D-specific bacterial signature identified in the NAFLD cohort. Functional inference analysis revealed that endotoxin biosynthesis pathways were significantly enriched in participants with NAFLD and T2D, compared with those with NAFLD alone. These findings may assist with the development of effective therapeutic approaches for metabolic diseases that are associated with specific bacterial signatures.
非酒精性脂肪性肝病（NAFLD）与2型糖尿病（T2D）密切相关，这两种代谢性疾病呈现双向影响。识别肝脏损伤或糖代谢受损所特有的微生物群特征，可能有助于理解肠道微生物群在NAFLD与T2D关系中的作用。在此，我们研究了一个经活检证实的亚洲NAFLD队列（n = 329；187名NAFLD参与者、101名NAFLD合并T2D参与者以及41名两者皆无的参与者），并确定了[具体菌群名称1]、[具体菌群名称2]和[具体菌群名称3]为与NAFLD和T2D严重程度相关的主要分类群，而[具体菌群名称4]和[具体菌群名称5]是NAFLD所特有的。特别是，与严重肝脏病理和T2D均相关的分类群也与糖尿病标志物显著相关，如空腹血糖和糖化血红蛋白。肠型分析表明，与韩国健康双胞胎队列（n = 756）相比，NAFLD参与者中[具体菌群名称6]的比例显著更高，而[具体菌群名称7]的比例更低。然而，T2D无法与NAFLD明确区分。对一个独立的T2D队列（n = 185）的分析使我们能够验证在NAFLD队列中确定的T2D特异性细菌特征。功能推断分析显示，与仅患有NAFLD的参与者相比，并发性NAFLD和T2D的参与者中内毒素生物合成途径显著富集。这些发现可能有助于开发针对与特定细菌特征相关的代谢性疾病的有效治疗方法。
