Microbiome alterations and host-pathogen interactions in paratuberculosis: A one health perspective

Paratuberculosis is a chronic ruminal-enteric infection caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has significant economic, trade, and public health implications. In addition to evading host immunity, MAP modulates the gut microbiome, resulting in dysbiosis that exacerbates disease progression. A conceptual framework is proposed in which Johne's disease (JD) can serve as the paradigm of chronic infection, based on dysbiosis in microbial imbalance, immune escape, and pathogen survival in a self-sustaining loop, as in human tuberculosis and Crohn's disease. This review evaluates the evidence on MAP-induced microbiome alterations and their impact on host-pathogen relations, immune responses, and metabolic processes in cattle, sheep, goats, and other ruminants. JD-associated dysbiosis is characterized by reduced microbial diversity, depletion of butyrate-producing taxa (e.g., Ruminococcaceae and Lachnospiraceae), enrichment of pro-inflammatory Enterobacteriaceae, and disruption of short-chain fatty acid (SCFA) metabolic pathways. Recent studies suggest that such alterations in microbes can be the initial signs of diagnosis and pre-treatment components, such as probiotics, prebiotics, dietary modifications, and microbiome-based vaccinations. This summary bridges the research on the veterinary and human microbiome, revealing that MAP-Microbiome interactions reflect immunological evasion and microbial persistence schemes observed with other intracellular pathogens. Evidence across species and disciplines highlights the interdependence between host microbiome stability, pathogen persistence, and disease progression. However, variances between studies show the need to adopt standardized methodologies, longitudinal studies, and multi-omics designs to establish whether dysbiosis precedes or follows MAP infection. The review is the first to combine molecular, immunological, and microbiome-level data into the One Health concept of MAP persistence. Moreover, this review takes a One Health approach where the investigation of MAP-induced dysbiosis offers an understanding of chronic inflammation, microbial ecology, and persistence strategies applicable to veterinary as well as human health. This way, we can emphasize the diagnostic, therapeutic, and translational opportunities of microbiome-based interventions in JD using a One Health model that connects ruminant disease to human inflammatory bowel diseases, including Crohn's disease.