Microbiome Engineering in Dairy Cattle: A Critical Review of Strategies for Disease Resistance, Productivity, and Sustainable Farming.

Dairy production currently faces three converging challenges: the escalation of antimicrobial resistance (AMR), rising global food demand, and stricter regulatory requirements for reducing enteric methane emissions. This review evaluates probiotics, prebiotics, fecal microbiota transplantation (FMT), metagenomic tools, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based synthetic biology for dairy cow microbiome engineering, applying a Technology Readiness Level (TRL) 1-9 framework to assess the translational maturity of each strategy. The quantitative ranges below are from individual controlled or field studies unless indicated otherwise, and they represent the variation from study to study in different breeds, feeds, and stages of lactation, as well as in management systems. A systematic literature search was conducted across five major databases for the period 2020-2026. Applying the TRL framework revealed that conventional probiotics have reached field-ready maturity (TRL 7-8), boosting milk yield by 0.5-1.5 kg/d and lowering somatic cell counts by 20-40%. Calf gut maturation was found to be two to three weeks faster when FMT was used (TRL 5-6). Controlled conditions (TRL 2-3) showed a 10-20% reduction in methane emissions using engineered rumen bacteria (CRISPR). Intervention failures primarily stem from host-microbiome misalignment rather than microbial product design. The key translational gap is shifting from uniform herd-level to precision-guided individualized dosing. Standardized data infrastructure, regulatory frameworks for engineered biologics, and integration with precision livestock farming platforms are required to reduce antibiotic use and lower methane emissions within a One Health framework.