Tolerogenic probiotics and gut-brain axis: targeting pain receptors in neuroimmune disorders

Tolerogenic probiotics, including Lactobacillus and Bifidobacterium species, offer significant therapeutic potential for neuroimmune disorders by modulating the gut-brain axis to promote immune tolerance and reduce inflammation. These probiotics influence key cell types, such as enteroendocrine cells (EECs), intestinal epithelial cells (IECs), and enteric glial cells (EGCs), enhancing gut barrier integrity and regulating hormone secretion (e.g. GLP-1, serotonin). They also modulate pain receptors, including transient receptor potential vanilloid 1 (TRPV1), cannabinoid (CB1, CB2), opioid (mu, kappa), and serotonin (5-HT) receptors, to alleviate visceral and neuropathic pain hypersensitivity. Despite promising preclinical evidence, challenges such as inconsistent dosing protocols, strain-specific efficacy, and limited large-scale clinical trials hinder clinical translation. This review synthesizes the mechanisms by which tolerogenic probiotics target the gut-brain axis and pain receptors, highlighting research gaps and proposing directions for personalized therapies and standardized clinical approaches.