摘要:Impaired thermoregulation and lowered average daily gains (ADG) result when livestock graze toxic endophyte (Epichloë coenophialum)-infected tall fescue (E ) and are hallmark signs of fescue toxicosis (FT), a disease exacerbated by increased temperature and humidity ( temperature-humidity index; THI). We previously reported FT is associated with metabolic and microbiota perturbations under thermoneutral conditions; here, we assessed the influence of E grazing and THI on the microbiota:metabolome interactions. Using high-resolution metabolomics and 16S rRNA gene sequencing, plasma/urine metabolomes and the fecal microbiota of Angus steers grazing non-toxic or E tall fescue were evaluated in the context of THI. E grazing affected the fecal microbiota profile; THI conditions modulated the microbiota only in E steers. E also perturbed many metabolic pathways, namely amino acid and inflammation-related metabolism; THI affected these pathways only in E steers. Integrative analyses revealed the E microbiota correlated and co-varied with the metabolomes in a THI-dependent manner. Operational taxonomic units in the families Peptococcaceae, Clostridiaceae, and Ruminococcaceae correlated with production parameters (e.g., ADG) and with multiple plasma/urine metabolic features, providing putative FT biomarkers and/or targets for the development of FT therapeutics. Overall, this study suggests that E grazing increases Angus steer susceptibility to THI, and offers possible targets for FT interventions.