Understanding how the tryptophan-kynurenine pathway is regulated in different tissues, and the diverse biological activities of its metabolites, has become of interest to many areas of science. The bioavailability of tryptophan can be affected by factors that range from gut microbiome composition to systemic inflammatory signals. Gut-resident bacteria can directly absorb tryptophan and thus limit its availability to the host organism. The resulting metabolites can have local effects on both microbiome and host cells and even mediate interspecies communication. In addition, the biochemical fate of absorbed tryptophan will be affected by cross-talk with other nutrients and even by individual fitness, because skeletal muscle has recently been shown to contribute to kynurenine metabolism.
In this Wednesday, June 1, 2016 photo, Amanda Evans-Clark looks over photos of her husband, Joe Clark, and their daughter at their home in Carmel, Ind. He died of advanced colon cancer at 31, after a year of chemotherapy and last-ditch major abdominal surgery. The decision to end treatment had a surprise effect on Clark and his wife. "It was a whole new way of thinking to wrap our minds around," Evans-Clark recalled. No more "fight mode," she said.
Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive form of kidney cancer and undergoes extensive metabolic reprogramming. Courtney et al. infused a glucose isotope into patients with primary ccRCC who were undergoing surgery and traced metabolic and isotopic flux. Compared with cells of the adjacent kidney, tumor cells exhibited prominent glycolysis, whereas the presence of tricarboxylic acid (TCA) cycle metabolites (indicating glucose oxidation) was diminished. In one patient who was infused with an acetate isotope (acetate is a direct substrate of the TCA cycle), low TCA cycle turnover of metabolites was also observed. This phenomenon describes the Warburg effect of metabolism in ccRCC and highlights metabolic differences between different types of cancer.
How does the gut microbiota shape the composition and function of distal host organs, despite being segregated in the gut? Uchimura et al. used stable isotope tracing to show that microbial metabolites penetrate host tissues and fluids to influence host immunological and metabolic signaling networks. However, metabolite impact is modulated by a high rate of urinary excretion of microbial products. Furthermore, secretory immunoglobulin A antibodies limit bacterial dwell times in the small intestine, which also ameliorates host exposure to microbial metabolites. The joint effect contributes to resolving gut function as both nutrient gateway and barrier.
DNA isn't the only molecule we could use for digital storage. It turns out that solutions containing sugars, amino acids and other small molecules could replace hard drives too. Jacob Rosenstein and his colleagues at Brown University, Rhode Island, stored and retrieved pictures of an Egyptian cat, an ibex and an anchor using an array of these small molecules. They say the approach could make storage that is less vulnerable to hacking and that could function in more extreme environmental conditions. Inspired by recent research showing that it is possible to store data on DNA, Rosenstein's team wanted to see if smaller and simpler molecules could also encode abstract information.