Free Radic Biol Med. 2026 Sep 9;256:441-460. doi: 10.1016/j.freeradbiomed.2026.09.006. Online ahead of print.

ABSTRACT

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a rising global prevalence, posing serious short-term and long-term health threats to both mothers and offspring. This review repositions GDM as a systemic disorder in which oxidative stress acts as a proposed mechanistic hub, linking upstream risk factors to downstream pathophysiology. We first examine how "upstream" factors-including genetic susceptibility, pre-conception status, and environmental exposures-converge to promote a state of pathological redox imbalance. We then examine key mechanistic pathways through which oxidative stress is thought to contribute to systemic insulin resistance and pancreatic β-cell failure, highlighting novel pathways involving intercellular communication via tunneling nanotubes and exosomes. Furthermore, we explore the downstream cascade, where oxidative stress may program maternal accelerated biological aging and multi-organ offspring disease trajectories through nuclear epigenetic programming and mitochondrial dysfunction programming, leaving what has been termed a persistent "metabolic memory". Consequently, this review evaluates emerging strategies that target oxidative stress for early prediction and precision intervention. Early prediction models based on direct redox biomarkers and multi-omics signatures hold potential to shift diagnosis from late-gestation oral glucose tolerance test (OGTT) to first-trimester risk stratification. Current supporting evidence draws from human epidemiological associations, ex vivo placental analyses, and experimental models. However, direct causal and interventional validation in pregnant women remains limited. Integrating targeted redox risk stratification and precision interventions into a life-course clinical framework may help interrupt the intergenerational transmission of metabolic disease initiated by GDM.

PMID:42716407 | DOI:10.1016/j.freeradbiomed.2026.09.006

J Vis Exp. 2026 Sep 1;(235). doi: 10.3791/73747.

ABSTRACT

Liver resection and liver transplantation remain cornerstone treatments for many hepatobiliary diseases, yet postoperative infection, impaired liver regeneration, and post-hepatectomy liver failure (PHLF) remain serious complications. Perioperative stressors can disrupt the gut-liver axis by altering the intestinal microbiota, epithelial barrier integrity, microbial metabolites, bile acid signaling, and host immunity. This review examines how these alterations relate to clinical outcomes and evaluates evidence for microbiota-targeted interventions, including probiotics, synbiotics, nutritional optimization, antibiotic stewardship, bile acid modulation, and emerging multiomics strategies. We distinguish liver resection from living-donor and deceased-donor liver transplantation because the patient populations, graft or remnant anatomy, ischemia-reperfusion exposures, immune status, and outcome definitions differ. Clinical evidence most consistently supports selected pro-/synbiotic strategies for reducing postoperative infection in higher-risk settings, whereas microbiome-based prediction of PHLF, fecal microbiota transplantation (FMT), bile acid-directed therapy, and precision multiomics-guided pathways remain investigational. Future work should use transparent literature identification, standardized perioperative protocols, risk-defined populations, external validation, and prospective multicenter trials. A better understanding of gut-liver interactions may help preserve beneficial host-microbial signals while limiting translocation and inflammation during recovery.

PMID:42683887 | DOI:10.3791/73747