The Gut Microbiota-Neuroimmune Axis Regulates Eosinophil Extracellular Traps and Their Role in Cancer Immunotherapy

The gut microbiota functions as a metabolically active microbial ecosystem that engages in bidirectional communication with the host nervous and immune systems, thereby contributing to homeostasis and disease pathogenesis. Eosinophil extracellular traps (EETs)-web-like structures composed of DNA and granule proteins released by activated eosinophils-exert context-dependent roles in host defence and immune regulation, with both pro-inflammatory and anti-inflammatory effects. Their function in tumour immunity, however, remains controversial. This review summarizes recent advances in understanding how the gut microbiota regulates eosinophil function and EET formation through the neuroimmune axis, encompassing the vagus nerve, neurotransmitters, and neuropeptides. We focus on the role of this regulatory network within the tumour microenvironment and discuss its potential influence on the efficacy of immune checkpoint inhibitors and the development of immune-related adverse events. By integrating evidence across microbial metabolism, neural signalling, and eosinophil biology, we aim to delineate the molecular mechanisms underlying this multilevel network and to provide a theoretical framework for anti-tumour strategies that co-target the gut microbiota and the neuroimmune axis, with the goal of improving immunotherapy outcomes while limiting treatment-related toxicity.