Microbiota-immune crosstalk in livestock: implications for tick-borne disease control.

Globally, livestock health, which impacts animal welfare and agricultural productivity, is continuously threatened by tick-borne diseases (TBDs). The growing issues of acaricide overuse in livestock, emerging resistance, and vector adaptation to climate change require novel and sustainable intervention strategies. Recent advances in microbiome research reveal how host and vector microbiota influence immune responses, particularly through natural antibodies (nAbs) that modulate vector competence and pathogen transmission. In livestock, nAbs targeting microbial glycans are heritable, measurable, and linked to health outcomes. In cattle, nAb titers to bacterial antigens are associated with mastitis risk and longevity, while in pigs, early-life nAb levels are proposed as resilience markers. Studies in poultry further demonstrate the importance of high nAb phenotypes for health and production. These findings highlight nAbs as both immunological markers and potential targets for genetic selection to improve disease resistance. Emerging interventions, such as anti-microbiota vaccines and immunobiotics, aim to modulate nAb repertoires, disrupt pathogen colonization, and enhance disease resilience. Additionally, microbial glycans serve as key targets for inducing cross-reactive immunity against TBDs. Manipulation of the livestock microbiota through diet, probiotics, and prebiotics shows promise in diversifying nAb profiles and improving robustness against infection. Despite these advances, research gaps remain, particularly in establishing causality and practical feasibility in livestock systems. This review emphasizes the need for integrative research across immunology, microbiology, and veterinary sciences to leverage microbiota-immune interactions in enhancing livestock resilience against TBDs, exploring how nAbs shaped by the gut microbiota can modulate tick microbiomes and impact pathogen transmission.