Review links bacterial inflammation, NETs and MMP activation to gallstone formation

A 2026 review in Molecular Biology Reports proposes a unified immunometabolic framework for gallstone disease, focusing on the coordinated roles of bacterial infection, neutrophil extracellular traps (NETs) and matrix metalloproteinase (MMP) activation. The article is a literature review rather than a new clinical trial or experimental study, and the available evidence consists of its abstract.

The abstract states that gallstone disease is a prevalent hepatobiliary disorder involving interactions among metabolic imbalance, biliary dysfunction and chronic inflammation. Although cholesterol supersaturation and impaired gallbladder motility are described as well established, the review examines how immune and metabolic processes may contribute to gallstone formation. It focuses specifically on the relationship between biliary bacterial colonization, inflammatory signalling, NET formation and MMP activity.

According to the abstract, bacterial colonization of the biliary tract can trigger inflammatory signalling pathways, cytokine release and oxidative stress. These processes are associated with activation of MMPs, which the review says may disrupt extracellular-matrix integrity and the protective mucin barrier. Such changes are presented as promoting cholesterol-crystal nucleation and retention in the gallbladder. In parallel, NETs are described as structural scaffolds that may enhance crystal aggregation and help stabilize gallstone growth.

The review further argues that bile-acid toxicity and altered lipid metabolism can intensify epithelial injury and inflammatory responses, reinforcing a pro-lithogenic environment. By connecting infection-associated inflammation, extracellular-matrix changes, NET scaffolds, bile-acid effects and lipid metabolism, the proposed framework links biliary and immune processes to gallstone development. The abstract identifies NET formation, MMP activity and bile-acid-mediated toxicity as potential molecular targets and possible avenues for therapeutic investigation, but it does not report tested treatments, clinical outcomes or evidence that targeting these pathways prevents gallstones. Because the source provided is an abstract, the review’s detailed methods, extent of literature coverage and limitations cannot be assessed from the available material.

Subject of Research: Immunometabolic mechanisms implicated in gallstone formation

Article Title: Immunometabolic crosstalk in gallstone disease: driving roles of bacterial infection, NETs and MMP activation

Article References: Murali, S., Krishna, R. B. D., Krishnamurthy, N., Balu, J., Ram, P. N., Vijayaraghavan, S., Shanmugam, R. K., P, H. K., & Francis, A. M. (2026). Immunometabolic crosstalk in gallstone disease: driving roles of bacterial infection, NETs and MMP activation. Molecular Biology Reports, 53(1), Article 1564. https://doi.org/10.1007/s11033-026-12741-7

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12741-7

Keywords: gallstone disease, bacterial infection, neutrophil extracellular traps, matrix metalloproteinases, bile acids, cholesterol crystallization, inflammation, gallbladder biology, Immunometabolic, crosstalk, gallstone, disease