The bacteria that inhabit the mammalian gastrointestinal tract, referred to as the microbiota, generally benefit the overall host physiology and well-being. Recent studies suggest that intestinal microbiota are also major contributors to a complex signaling network in the human gastrointestinal tract. Specifically, it is hypothesized that bacterial molecules produced by the intestinal microbiota will be recognized by intestinal cells as a result of their close spatial association within this ecological niche. At the core of signaling network are tryptophan metabolites that appear to contribute to both the intestinal and microbiota fitness. This project will test the hypothesis that tryptophan metabolites affect dentritic cells in a way that benefits the intestinal environment as well as the microbiota to create a beneficial gut mucosal ecology.
BROADER IMPACTS: This project will investigate the communication of host cells with signals produced by the intestinal microbiota, which is an important factor in human/microbiota symbiotic relationship. The educational and outreach component of this proposal focuses on two activities to increase the number of underrepresented students that pursue advanced degrees in biological sciences. First, the Principal Investigator serves as a role model for underrepresented students and has established a continuous pipeline of undergraduate students that receive research training in the PI's laboratory. Second, this project will develop an institutional program that creates opportunities for the Texas A&M Hispanic Minority Serving Institution (HSI) in the Texas A&M University System. These students are prepared research and training in graduate or medical school at the Texas A&M Health Science Center.
Dr. Alaniz, in close collaboration with Dr. Arul Jayaraman, has succeeded in the objectives of this project: 1) the microbiota metabolei indole was characterized to be a natural and abundant chemoeffector (interkingdom signal) present in the healthy GI tract of mice and humans. 2) The microbiota metabolite indole influenced GI tract ecology by preventing the colonization with bacteria (Salmonella typhimurium) that are not natural members of the GI tract community (microbiota). [ Rational identification of diet-derived postbiotics for improving intestinal microbiota function. Klemashevich C, Wu C, Howsmon D, Alaniz RC, Lee K, Jayaraman A. Curr Opin Biotechnol. 2014 Apr;26:85-90. doi: 10.1016/j.copbio.2013.10.006. ] 3) indole signals salmonella to decrease the expression of Type 3 secretion systems (i.e., T3SS-1) necessary to colonize the host GI tract and compete with endogenous members of the GI tract microbiota; indole appears to ofunction as a major "colonization resistance" signal for invading bacteria. [manuscript submitted] 4) we have identified that indole not only signals endogenous microbiota and bacterial species that invade the GI tract ecosystem, but also signals host cells (dendritic cells) in a manner (reduce inflammation) that favors overall GI tract host and microbial ecological homeostasis. [manuscript submitted] 5) we have identified the host receptor for microbiota-derived indole as the aryl hydrocarbon receptor (AhR; also know as the xenobiotic receptor). [ Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Jin UH, Lee SO, Sridharan G, Lee K, Davidson LA, Jayaraman A, Chapkin RS, Alaniz R, Safe S. Mol Pharmacol. 2014 May;85(5):777-88. doi: 10.1124/mol.113.091165. ]
