<i>Heyndrickxia coagulans</i> as a next-generation probiotic: current evidence and future perspectives

<i>Heyndrickxia coagulans</i>, a spore-forming probiotic, has garnered significant attention due to its exceptional tolerance to gastric acid and heat, alongside its multifaceted therapeutic potential. This review systematically delineates the unique biological characteristics of this bacterium, which include high survivability mediated by its spore form (retaining 73% viability after microwave treatment at 260 °C), dual lactate fermentation pathways, and plasticity in ATP synthesis that depends on pH and growth rate. Clinical evidence supports its efficacy in managing metabolic disorders (<i>e.g.</i>, type 2 diabetes and non-alcoholic fatty liver disease), gastrointestinal conditions (<i>e.g.</i>, constipation and irritable bowel syndrome), and neuropsychiatric disorders (<i>e.g.</i>, depression and Alzheimer's disease). The underlying mechanisms involve the production of short-chain fatty acids (SCFAs), modulation of the TLR4/MyD88/NF-κB signaling pathway, and suppression of oxidative stress. Notably, therapeutic effects are strain-specific: <i>H. coagulans</i> MTCC 5856 (2 × 10¹⁰ CFU day^-1) significantly reduces abdominal distension (<i>P</i> < 0.01), while the strain Unique IS-2 alleviates anxiety-like behaviors by upregulating hippocampal BDNF. Although toxicological assessments establish a no observed adverse effect level (NOAEL) of >1000 mg kg^-1 in rodent models, its limited capacity for intestinal colonization presents a clinical challenge. Future research should prioritize large-scale clinical trials, multi-omics mechanistic investigations, and the development of synbiotic formulations to fully realize its potential as a next-generation therapeutic agent.