Mastitis is a severe disease in cows that decreases milk yield and quality in dairy farms around the world. Although pathogenic infection of the mammary gland is a major cause, the gut microbiota is also thought to play a critical role. Studies have shown that mastitis is associated with gastrointestinal imbalance caused by the acid build-up associated with a high-grain diet, but the direct link between gut microbes and mastitis remains unclear. To address this gap, researchers investigated the microbes and their metabolites in the gut of cows fed a high-grain diet. Findings revealed elevated levels of sialic acid. Separate experiments in mice showed that supplementation with sialic acid aided the proliferation of Enterobacteriacea. These microbes damage the gut barrier, allowing toxins to enter the intestine and cause local inflammation, which then progresses to systemic inflammation when the toxins enter the blood. Persistent systemic inflammation disrupts the blood-milk barrier, ultimately inducing mastitis. Although the effects of different types of sialic acid on gut imbalance and mastitis remain unexplored, the connections observed between the microbiota, gut, and mammary gland may enable future.