Correspondence to editorial on “MicroRNA isomiRs reveal novel pathways linked to disease activity and fibrosis in MASLD” David William Salzman, Stephen Aurelien Hoang, Arun Jayant Sanyal Clinical and Molecular Hepatology.2026; 32(3): e387. CrossRef
The knowledge accumulated over the past two decades has revealed that the natural history of metabolic dysfunction-associated steatotic liver disease (MASLD) and the drivers of the disease severity are not only complex but also exhibit variation among patients. This intricate clinical scenario entails major therapeutic and management implications. In this review, we provide a comprehensive examination of recent advancements in our understanding of MASLD heterogeneity, drawing insights from multiomics and panomics studies. The discussion herein explores the instrumental role of panomics in MASLD research, elucidating the potential for the identification of molecular subtypes that exhibit divergent survival outcomes or heterogeneous responses to various treatments. Furthermore, we provide insights into the challenges in addressing disease heterogeneity and potential solutions. Finally, the most advanced technological advancements and prospective research directions in the domain of MASLD research are delineated, with the objective of facilitating the implementation of personalized diagnosis and interventions.
Citations
Citations to this article as recorded by
Semaglutide in MASH with F2-F3 fibrosis: a holistic perspective on the ESSENCE phase 3 trial Carlos Jose Pirola, Silvia Sookoian Metabolism and Target Organ Damage.2026;[Epub] CrossRef
Mapping the genomic landscape of MASLD: A framework for molecular subtyping and precision hepatology Carlos José Pirola, Silvia Sookoian Med.2026; 7(6): 101131. CrossRef
Reply to correspondence on “Comparative risk of fibrosis progression with sodium-glucose cotransporter-2 vs. dipeptidyl peptidase-4 inhibitors in metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus with low-to-intermediat Yang-Hsiang Lin, Ching-Chih Hu, Chih-Lang Lin Clinical and Molecular Hepatology.2026; 32(3): e434. CrossRef
Beyond the canonical sequence: IsomiRs as modulators and drivers of MASLD progression: Editorial on “MicroRNA isomiRs reveal novel pathways linked to disease activity and fibrosis in MASLD” Carlos Jose Pirola Clinical and Molecular Hepatology.2026; 32(3): 1452. CrossRef
From indirect regulation to multi-layered metabolic control in MASLD: Multi-receptor agonism and microbiota–metabolite functional convergence Sini Zhou, Ling Dong Pharmacological Research.2026; 231: 108369. CrossRef
Background/Aims Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.
Methods Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.
Results There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.
Conclusions This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
Citations
Citations to this article as recorded by
Sex and gender differences in metabolic dysfunction-associated liver disease Rishitha Penmetsa, Sasha Kapil, Lisa B. VanWagner Indian Journal of Gastroenterology.2026; 45(2): 192. CrossRef
New Definition, New Point of View: Sex and Gender Interpretation of MASLD—Interpretation of Guidelines and Review of the Literature Massimo De Luca, Rita Verdoliva, Anna Lombardi, Antonio Giorgio Gastroenterology Insights.2026; 17(1): 7. CrossRef
The Gut–Liver Axis in MASLD: From Host–Microbiome Crosstalk to Precision Therapeutics Ji Zhou, Bowen Zhu, Ziqian Bing, Tingting Wang, Yue Zhao Microorganisms.2026; 14(2): 471. CrossRef
Sex-specific dynamics of MASLD reveal early hepatic and extrahepatic metabolic deterioration in females despite long-term protection Maria Repollés-de-Dalmau, Anna Marsal-Beltran, Catalina Núñez-Roa, Joan Vendrell, Victòria Ceperuelo-Mallafré, Sonia Fernández-Veledo Biology of Sex Differences.2026;[Epub] CrossRef
Sex-specific cardiometabolic phenotypes in MASLD: 3PM-centric stratification and trajectory mapping for proactive risk assessment Carlos José Pirola, Luis Diambra, Tomas Fernández Gianotti, Silvia Sookoian EPMA Journal.2026; 17(2): 387. CrossRef
Dysregulation of the Gut-Adipose Tissue-Liver Axis: a Possible Mechanism Behind the Relationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Susanna Longo, Tommaso Giovanni Rinaldi, Jose Manuel Fernández-Real, Massimo Federici Current Diabetes Reports.2026;[Epub] CrossRef
Correspondence to letter to the editor on “Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunctionassociated steatotic liver disease” Eiji Kakazu, Masaaki Mino, Tatsuya Kanto Clinical and Molecular Hepatology.2026; 32(2): e235. CrossRef
Sex differences in the gut microbiome and related metabolites: role in cardiometabolic disease Yi Wang, En Cheng, Brandilyn A. Peters-Samuelson Gut Microbes.2026;[Epub] CrossRef
MASLD: Prevalence, Mechanisms, and Sex-Based Therapies in Postmenopausal Women Ilaria Milani, Marianna Chinucci, Frida Leonetti, Danila Capoccia Biomedicines.2025; 13(4): 855. CrossRef
Characteristics of serum bile acid profiles among individuals with metabolic dysfunction-associated steatotic liver disease Sheng Lyu, Jiani Yang, Xin Xin, Qinmei Sun, Beiyu Cai, Xin Wang, Ziming An, Jian Sun, Yiyang Hu, Lei Shi, Qin Feng, Xiaojun Gou BMC Gastroenterology.2025;[Epub] CrossRef
Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease Chao Cui, Shuai Gao, Jingfei Shi, Kai Wang Gut and Liver.2025; 19(4): 479. CrossRef
Triglyceride-glucose-waist circumference index: A powerful tool for metabolic dysfunction-associated steatotic liver disease Bryan Adrian Priego-Parra, Berenice M Román-Calleja, Rocio Gallego-Duran, Jordi Gracia-Sancho, Jose Antonio Velarde Ruiz-Velasco, Jose Maria Remes-Troche World Journal of Hepatology.2025;[Epub] CrossRef
Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery Stavros P. Papadakos, Chara Georgiadou, Eva Kassi, Rallia-Iliana Velliou, Antonios Chatzigeorgiou Expert Opinion on Drug Discovery.2025; 20(12): 1683. CrossRef
ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH Xiao Wen, Keyan Wu, Mengyao Wang, Zihan Ma, Tao Wang, Jing Zhang, Bei Wang, Siyuan Chen, Jingyi Wang, Siyue Chen, Fan Yang, Chuwei Liu, Xianyang Chen, Lu Deng, Yafan Cheng, Qing Robert Miao, Baofa Sun, Xiongzhong Ruan, Kai Li, Yajun Duan, Wenquan Hu Nature Communications.2026;[Epub] CrossRef
Early portal hypertension in metabolic dysfunction-associated steatotic liver disease: a concise review Iván López-Méndez, Eva Juárez-Hernández, Juan Pablo Soriano-Márquez, Misael Uribe, Graciela Castro-Narro Expert Review of Gastroenterology & Hepatology.2025; 19(7): 755. CrossRef
The effects of next generation probiotics on metabolic dysfunction-associated steatotic liver disease: a parallel, double-blind, randomized, placebo-controlled trial Sung-Min Won, Hyunchae Joung, In Gyu Park, Sang Hak Han, Young Lim Ham, Ji Sook Han, Yoojin Kwon, Dong Joon Kim, Ki Tae Suk Journal of Translational Medicine.2025;[Epub] CrossRef
Correspondence on Editorial regarding “Identification of signature gene set as highly accurate determination of MASLD progression” Sungju Jung, Sumin Yoon, Jong Hoon Park, Yeon-Su Lee, Kyung Hyun Yoo Clinical and Molecular Hepatology.2024; 30(2): 287. CrossRef
First
Prev
