The Gut-Liver Axis in Health and Disease: Microbial Crosstalk, Systemic Drivers, and Therapeutic Frontiers

The gut-liver axis is a core area in biomedical research, characterized by intricate and bidirectional crosstalk between the intestinal microbiome and hepatic physiology. Over the last decade, mounting evidence has identified the axis as a key contributor to metabolic, inflammatory, hepatic, and even systemic disorders. Notably, dysregulation within this axis is now recognized as a driver of escalating diseases such as non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and hepatocellular carcinoma. Studies have identified profound changes in microbial composition and metabolite production. Additionally, disruptions in mucosal immune responses and alterations in neural and endocrine signaling play crucial roles. While our mechanistic understanding is advancing—linking gut-derived entities, such as short-chain fatty acids, bile acids, and pathogen-associated molecular patterns to liver health—key questions remain regarding the directionality, causality, and clinical translation of these interactions. Importantly, the influence of oral microbiome dysbiosis, psychosocial stress, and environmental exposures on the gut-liver axis has emerged as a rapidly expanding area of research, with new studies suggesting multi-niche and multi-system involvement that demands integrated research. Emerging evidence also highlights the role of the gut–brain–liver axis, where bidirectional communication between the central nervous system, microbiome, and liver further modulates metabolic and inflammatory outcomes.This Research Topic aims to synthesize and advance our comprehension of the microbial, systemic, and environmental forces shaping the gut-liver axis in both health and disease. We seek to clarify the molecular pathways and cross-system drivers that underpin liver pathology and to explore how diverse microbiomes along the digestive tract (oral and intestinal) contribute to hepatic inflammation, immune activation, and metabolic imbalance. Through mechanistic, translational, and comparative research, this initiative endeavors to pinpoint new diagnostic markers, therapeutic strategies, and opportunities for cross-disciplinary synergy—especially those that unite insights from hepatology, microbiology, immunology, and psychoneurobiology.The scope of this Research Topic encompasses studies in vertebrate species that dissect microbial, neuroimmune, and metabolic dimensions of the gut-liver axis, while acknowledging the multifaceted nature of microbe-host interactions. We encourage submissions that address causal mechanisms, translational potential, and experimental approaches across taxa. To gather further insights in the integrated field of gut-liver axis biology, we welcome original research articles, reviews, mini-reviews and all types of articles accepted by the journal addressing, but not limited to, the following themes:o Intestinal and oral microbiome signatures associated with the development and progression of hepatic diseaseso Microbial metabolites and their mechanistic effects on liver inflammation, fibrosis, and metabolismo Effects of psychological stress and neuroendocrine regulation on oral-gut-liver crosstalko Host-microbiome immune crosstalk involving mucosal, neural, and hepatic signaling pathwayso Effects of Lifestyle, diet, and environmental factors on the microbiome and gut-liver homeostasiso Interventional strategies: Prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and dietary modulationo Comparative and translational studies using vertebrate models to identify conserved and divergent microbial mechanisms Topic editors: Swayam Prakash, Peerzada Tajamul Mumtaz, Jing Jin, Karthiyaini Damodharan, Lemonica Koumbi Source: https://www.frontiersin.org/research-topics/79776/the-gut-liver-axis-in-health-and-disease-microbial-crosstalk-systemic-drivers-and-therapeutic-frontiers