Many studies have elucidated the pivotal significance of the gut microbiota in the pathogenesis of numerous diseases. Research has demonstrated that administering high-grain diets (HGDs) to ruminants to enhance growth performance results in subacute ruminal acidosis (SARA), which subsequently triggers rumen microbial dysbiosis. This dysregulation can result in inflammation within the gastrointestinal tract, disruption of the gastrointestinal barrier, and an increased risk of disease. Nevertheless, the precise underlying mechanism that governs the contribution of the ruminal microbiota to the development of gastrointestinal inflammation remains elusive. The objective of this study was to investigate the role and potential mechanisms of microbial dysbiosis in the context of gastrointestinal inflammation. An HGD was used to induce SARA in dairy goats, thus establishing a model of ruminal microbial dysbiosis. The findings of this study indicate that dairy goats with SARA exhibit significant gastrointestinal and systemic inflammation, which is associated with ruminal microbial dysbiosis. The transplantation of ruminal microbiota from SARA dairy goats in mice has been demonstrated to induce gastrointestinal inflammation and disrupt the gastrointestinal barrier, thereby leading to a systemic inflammatory response. Furthermore, ruminal microbial dysbiosis is involved in gastrointestinal inflammation through the promotion of ferritinophagy-ferroptosis via activation of the NCOA4/FTH signalling pathway. However, this process can be reversed following pretreatment with Fer-1. These findings suggest that the modulation of the ruminal microbiota could be a potential strategy to prevent inflammation in the gastrointestinal tract and even systemic inflammatory responses. Importance. SARA is a common nutritional metabolic disease in ruminants and has significant implications for animal welfare and performance. Research has shown a strong link between SARA-induced rumen flora disorders in ruminants and inflammatory diseases such as hepatitis, mastitis and endometritis. The results of the present study demonstrate that disorders of the rumen flora can disrupt the gastrointestinal barrier through the ferritinophagy-ferroptosis pathway, leading to the movement of harmful substances and the development of systemic inflammation and other related inflammatory diseases. This study offers a new theoretical basis for treating inflammatory diseases in ruminants.
