H9N2 influenza virus infections represent a significant respiratory health concern, yet the functional role of gut microbiota during infection progression remains poorly understood. Here, we show that H9N2 infection causes dose-dependent alterations in gut microbial communities in a mammalian infection model, particularly the depletion of Prevotella species. Prophylactic administration of Prevotella copri improved survival and clinical outcomes in infected mice by restructuring the gut microbiome, promoting beneficial bacteria, and suppressing pathogens. Metabolomic profiling revealed increased isovaleric acid levels in the intestine and serum. Isovaleric acid pretreatment reduced pulmonary inflammation, alleviated tissue damage, and preserved epithelial integrity. Isovaleric acid pretreatment alleviates lung inflammation, reduces tissue damage, and maintains epithelial integrity. Additionally, isovaleric acid mitigates infection caused by the H1N1 influenza virus. These findings highlight the immunomodulatory role of gut commensals and their metabolites in antiviral defense, offering a new approach to influenza virus treatment.

The discovery of regulated necrosis revitalizes the understanding of necrosis from a passive and accidental cell death to a highly coordinated and genetically regulated cell death routine. Since the emergence of RIPK1 (receptor-interacting protein kinase 1)-RIPK3-MLKL (mixed lineage kinase domain-like) axis-mediated necroptosis, various other forms of regulated necrosis, including ferroptosis and pyroptosis, have been described, which enrich the understanding of pathophysiological nature of diseases and provide novel therapeutics. Micronutrients, vitamins, and minerals, position centrally in metabolism, which are required to maintain cellular homeostasis and functions. A steady supply of micronutrients benefits health, whereas either deficiency or excessive amounts of micronutrients are considered harmful and clinically associated with certain diseases, such as cardiovascular disease and neurodegenerative disease. Recent advance reveals that micronutrients are actively involved in the signaling pathways of regulated necrosis. For example, iron-mediated oxidative stress leads to lipid peroxidation, which triggers ferroptotic cell death in cancer cells. In this review, we illustrate the crosstalk between micronutrients and regulated necrosis, and unravel the important roles of micronutrients in the process of regulated necrosis. Meanwhile, we analyze the perspective mechanism of each micronutrient in regulated necrosis, with a particular focus on reactive oxygen species (ROS).

Introduction: Aeromonas veronii remains a pervasive aquatic pathogen precipitating catastrophic economic depletion and threats to global food security. Conventional therapeutic modalities are constrained by inadequate stability, prohibitive costs, and biosafety risks. Methods: To address such challenges, an engineered Lactobacillus casei strain was developed to constitutively express the A. veronii outer membrane protein OmpAI through a tandem promoter system to ensure optimized antigen delivery. Results: Anal intubation with engineered L. casei in Channa argus stimulated compartmentalized mucosal immunity, evidenced by a six-fold elevation in hindgut IgT transcripts, significant infiltration of IgT ⁺ B cells, and pIgR mediated transcytosis, synchronized with systemic IgM activation. The probiotic treament accelerated pathogen clearance, improved survival rates to 42.9% compared to 12.5% in control group, and reorganized the commensal microbiome through a specific enrichment of beneficial Firmicutes . Discussion: This study elucidated a novel engineered-probiotic mucosal vaccination strategy for teleosts, providing a noninvasive, mucosal targeted immunoprophylactic strategy to decrease antibiotic dependency in aquaculture.