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.