Zhiheng Pei, MD, PhD

The common theme in our work is the effect on disease states by the microbial pressure that arises when a patient?s symbiotic bacterial biota is altered. Increasing evidence suggests an important role for chronic inflammation in many disease conditions associated with aging, such as atherosclerosis, cancers, diabetes, and even autoimmune diseases. The body contains about ten times as many commensal bacteria as human cells, 1 quadrillion versus 100 trillion. Under normal conditions, these commensal bacteria are essential for the development of the mucosal immune system, maintenance of the physiological environment, and the provision of essential nutrients. However, changes in the balance of the normal bacterial biota might induce pathogenesis. The analysis of bacterial biota is an innovative approach that could lead to discovering the etiology of a number of idiopathic chronic diseases that involve alteration of the normal microbial populations, and could provide a better understanding of pathogenesis in polybacterial diseases that are otherwise poorly explained by conventional disease models.

One project in my laboratory explores the role of bacterial biota in the development of esophageal adenocarcinoma in reflux-related disorders (R01CA97946). Our hypothesis is that gastric acid reflux selectively alters the normal microbial populations in the distal esophagus. Such a microenvironmental change may favor an overgrowth of bacteria that are inflammation prone, or produce carcinogenic metabolites that promote tumorigenesis. We are testing this hypothesis by defining the bacterial biota in the normal esophagus vs. that found in association with reflux disorders. Through comparison of these differences, we hope to identify the bacteria associated with reflux disorders, to explore how and why this association occurs, and to determine what role any microbial population shifts might play in tumorigenesis.

Another project relates to the etiology of idiopathic tonsillar hypertrophy, or ITH (R01AI063477). ITH is an obstructive lymphoproliferative disease that plays a pathogenic role in obstructive sleep apnea, failure to thrive, abnormal dental and facial growth, halitosis, and other ailments. ITH has also been implicated in the neurologic morbidity associated with sleep disorders, such as inattention and hyperactivity in children. In a significant number of cases, hypertrophic tonsils harbor large clusters of mixed bacterial populations referred to as metacolonies. Our hypothesis is that ITH is a manifestation of the immune reaction to antigens released from bacterial metacolonies in hypertrophic tonsils. We are testing this hypothesis by investigating the association between metacolony-common (MC) species and ITH, and by examining the specific roles played by these bacteria in the activation of B lymphocytes in ITH.

An extension of this work involves exploring the role of tonsillar metacolonies as a potential reservoir of pathogens for dental and periodontal diseases. This work is still at an early stage, but holds significant promise for developing novel therapeutic approaches to combat these prevalent illnesses.

My interest in the analysis of microbial biota in the human health context also extends into the clinical domain, where I am working with NYU Hospital Residents and Fellows on the application of new methodologies for disease diagnosis in clinical practice. In particular, we are pursuing the identification of uncultivable microbial agents in fixed tissue specimens through the use of molecular techniques.