Metabolomics and xenometabolomics: Applications to study metabolic health
Dr. Sean Adams is the Director of the Arkansas Children’s Nutrition Center where his research aims to understand the molecular processes that underlie metabolic disease and obesity. Although it is well known that health status affects the microbiome and that the microbiome affects health status, molecular signals linking gut microbes and host pathophysiology remain largely unknown. His lab applies metabolomics to gut microbiome metabolism, which they call xenometabolomics. During his talk, Dr. Adams focused on two topics. Firstly, how does microbial metabolism impact host physiology? To investigate this question, they have studied nitrogen, kidney, and liver metabolism in the context of an altered microbiome. They have found that dietary manipulation of the gut microbiome alters the host liver metabolome; there are reduced hepatic amino acids and urea cycle metabolites in mice feed a high starch diet. The same diet fed to experimental mice in a chronic kidney disease model ameliorates the kidney disease. They believe that the high starch diet increases the density of beneficial bacteria which then act as a nitrogen sink to reduce the nitrogen load on the kidney. Further, they reason that the changed metabolites from the changed microbiome reduces uremic solutes. Second, Dr. Adams discussed how host physiological states impact the microbe population and biochemistry. In a study of adult human women, they found that xenometabolites—specifically, cis-3,4-methylene heptanoyl carnitine and aminomalonic acid— change with both acute exercise and with weight loss. They have also found the microbiome and xenometabolomics distinctively change during diabetes progression in a rat model. In fact, performing a “xenoscan” of the cecal metabolites can discriminate severity of disease in a rat model. Knowing this, his group hopes to investigate how we can use these altered metabolites to treat or identify disease. In summary, Dr. Adam’s group has shown that host microbiome cross talk involves a two-way street. They will continue to investigate the molecular factors involved in this communication and work towards improving our metabolic health by studying microbiota ecology and xenometabolism.