Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

This research investigates how a decrease in the amino acid citrulline might indicate a heightened risk of developing laminitis, a painful inflammatory disease often linked to sepsis, in horses. The study identifies potential implications for predicting and diagnosing this disease through serum metabolomics.

Background and Methodology

• The study begins by highlighting acute laminitis, an inflammatory ailment in horses that typically follows sepsis or systemic inflammation related to gastrointestinal disease. The authors suggest its similarity to human multiple organ dysfunction syndrome, with the initial organ failure in horses manifesting in the weight-bearing laminar epithelium of the foot.
• The researchers used metabolomics on blood samples collected from horses before (the control group, or Con) and after (the Laminitis group, or Lmn) the induced gastrointestinal-related sepsis. In the process, they found 1,177 mammalian and bacterial-origin metabolites in the equine serum.

Results and Findings

• Network and correlation analyses indicated a disruption in fatty acid metabolism in the Lmn group, as well as an increase in organic acids such as lactate.
• Notably, the concentrations of the amino acid citrulline were found to be reduced in the Lmn samples from all study animals. This led to the inference that citrulline could serve as a predictive biomarker to identify critically ill animals that are potential candidates to develop laminitis.

Establishment of Plasma Citrulline as a Predictive Biomarker

• To confirm this inference, the study established baseline plasma citrulline concentrations in another group of horses. The ability of citrulline to predict undesirable outcomes, such as laminitis or death, was then tested on critically ill horses.
• The study found significantly lower plasma citrulline levels in critically ill horses that eventually experienced unfavorable outcomes.
• This finding strongly suggests that citrulline could prove to be a useful biomarker for predicting laminar failure (which leads to laminitis) in horses suffering from sepsis. However, further research is needed to accurately determine a diagnostic cutoff.