Bridging soil health and human health: Mycobacterium vaccae as a keystone link

Mycobacterium vaccae (recently reclassified as Mycolicibacterium vaccae ) is a non-pathogenic, soil-dwelling bacterium increasingly recognized for its potential role in linking ecosystem health with human immune and mental health. This narrative review synthesizes current knowledge on the soil ecology of M. vaccae, pathways of human exposure, immunological and neurobiological mechanisms, and implications for public and planetary health, following a structured literature search of PubMed, Web of Science, and Scopus. Ecologically, M. vaccae is best documented for its capacity to degrade hydrocarbons and related xenobiotic pollutants, and forms part of diverse soil microbial communities. Human exposure occurs primarily through inhalation, dermal contact, and ingestion of soil-associated materials, with reduced exposure reported in urbanized environments. Immunologically, M. vaccae promotes immune tolerance by inducing regulatory T cells, tolerogenic dendritic cells, and anti-inflammatory cytokine profiles, providing mechanistic support for the “old friends” hypothesis. Preclinical evidence, largely from rodent models, demonstrates its influence on serotonergic signaling, neuroinflammation, and stress-related behaviors; human evidence remains limited to a small number of early-phase and observational studies, which constrains causal inference and limits generalization of preclinical neurobehavioral findings to clinical practice. Preclinical and preliminary clinical findings support applications for allergic and inflammatory conditions and use as a vaccine or cancer-therapy adjuvant, with a more limited and preliminary evidence base for neuropsychiatric indications. This review also discusses the ecological drivers of soil biodiversity loss and their possible relevance to public health, while highlighting gaps in safety data, independent replication, and methodological standardization that should be addressed.