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Overview: Diet, Enteric Bacterial Invasion, and Chronic Inflammation

Chronic inflammation is increasingly implicated in the pathophysiological processes of many diseases afflicting individuals of westernized societies including diabetes, atherosclerosis, and some cancers. Consumption of diets high in refined carbohydrates and fat, but low in fruits, vegetables, and whole grains appear to contribute significantly to these disease states. Our research efforts focus on delineating the role of diet in modulating insidious bacterial translocation, a process involving invasion of gut bacteria or their proinflammatory byproducts to extraintestinal sites. We hypothesize that this leakage of bacteria due to poor gut nutrition may be a potent trigger for the systemic inflammation underpinning insulin resistance, vascular dysfunction, and other metabolic derangements of aging and chronic disease.

Current approaches used to detect enteric bacterial invasion are relatively insensitive, including microbiological culture and classic techniques such as polymerase chain reaction (PCR) amplification of bacterial DNA. Thus, documentation of this event has mostly been confined to extreme inflammatory conditions such as sepsis, burn injury, peritonitis, blunt abdominal trauma, multiple organ dysfunction, etc. Low-level bacterial invasion is a much more difficult process to tract due to the trace amounts of microbes involved. Our interest in characterizing the link between bacterial invasion and subtle inflammatory signaling demands a methodology that is orders of magnitude more sensitive than the cited approaches. In an effort to directly link this event to systemic inflammation, we are developing molecular probes that enable tracking of these bacteria with greatly improved sensitivity compared to that of traditional PCR-based methods. These high sensitivity tools, that are designed to selectively “trap” DNA encoding bacterial 16s rRNA, open up many opportunities to investigate the role of gut bacterial invasion in human disease. In addition, the characterization of this event may offer an alternative explanation for the beneficial effects on health status of dietary fiber, fruits and vegetable intake, and metabolic substrates that enhance intestinal mucosal function. Furthermore, a better understanding of nutritional interventions that blunt the untoward, bacterial invasion-promoting effects of chemotherapeutic drugs, radiation therapy, parenteral nutrition, poor diet, and food allergy may also be gained. Through these studies we hope to provide a conceptual bridge between gut health, nutrition, and disease.

Another research focus of my laboratory involves the use of analytical techniques to quantitate small molecule analytes that report levels of oxidative stress, inflammation, and vascular dysfunction. Efforts have lead to the development of high sensitivity techniques that enable the detection of molecular damage to DNA and protein produced by normal metabolism and inflammatory response. Ongoing work focuses on the development of methods to monitor blood plasma levels of L-arginine, asymmetric dimethylarginine (ADMA, a potent inhibitor of nitric oxide synthase), and other amino acids whose levels affect vascular function and are markedly changed during inflammation. Such techniques will allow us to test the relationship between bacterial invasion and parameters of vascular function in animal models and affected individuals. We plan to implement both molecular approaches to examine the role of diet and enteric bacterial invasion in systemic chronic inflammatory states.

 

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