Inflammation-Associated Changes in Bioactive Proteins and Peptides of Bovine Milk: Evidence from Mastitis, Lameness, and Metabolic Disorders—A Review

Bovine milk contains bioactive proteins and encrypted peptide sequences whose abundance and availability may change during mammary or systemic inflammation. This narrative review critically evaluates evidence associated with subclinical mastitis, lameness-causing claw disorders, and periparturient metabolic disorders. Direct milk-level evidence is strongest for mastitis: increased somatic cell count and intramammary inflammation are generally associated with higher concentrations of milk haptoglobin, milk serum amyloid A (including mammary-associated serum amyloid A3, when isoform-resolved), lactoferrin, cathelicidins, and immunoglobulins, together with accelerated casein proteolysis. For lameness and metabolic disorders, evidence is substantially weaker and derives mainly from systemic acute-phase responses, broad milk metabolomic or compositional changes, and mechanistic hypotheses involving blood–milk barrier permeability and protease regulation. The review explicitly separates direct disease-defined milk evidence from systemic, broad omics, and mechanistic evidence. These alterations may influence biomarker performance, whereas processing consequences are best-established for mastitic milk. Their persistence after processing and digestion, and their biological effects in human consumers, remain largely unresolved. Future studies should combine diagnosis-specific cow health monitoring with milk proteomics and peptidomics. They should also assess the stability, bioaccessibility, and functionality of altered proteins and peptides during processing and digestion.