Research

Nanda Nanthakumar, PhD
Assistant Professor of Pediatrics

Phone: 617-726-4180
Fax: 617-726-4172
Email: nanthaku@helix.mgh.harvard.edu

Curriculum Vita

Fellows: Di Meng, MD, PhD; Weishu Zhu, MD; Alix Dubert-Ferrandon, PhD

The adult human gastrointestinal tract is colonized by a community of more than 450 interdependent species of bacteria that are the major components of a stable but dynamic microbial ecosystem known as the gut microbiota. The gut microbiota are now becoming recognized as part of an important mutualist relationship in which both the microbes and humans benefit. Mutualist association requires cross communication (crosstalk) between the microbiota and the epithelial lining of the gut. My lab focuses on the interaction between gut epithelium and gut microbiota in the newborn, during the transition from milk to solid food, and in mature young adults.

Pioneer bacterial species induce expression of fucosylated cell surface glycans by mammalian gut epithelium. This enables colonization by additional fucose-adherent bacteria that direct the succession of microbial colonization toward the complex microbial ecosystem of the adult gut. We have identified a mechanism whereby pioneer bacterial species initiates communication with the gut epithelium at the genesis of colonization that leads to alteration of gene expression and generation of fucosylated gut surface.

Probiotics is another group of bacteria within our gut that, when present in sufficient quantities, can exert health benefits by preventing or reducing the severity of enteric pathogen infection. The bacteria-epithelial crosstalk between probiotic bacteria and gut epithelium suggests a specific mechanism by which probiotic bacteria can prevent infection by a wide variety of enteric pathogens. We are identifying nutrients that enhance colonization by probiotic bacteria that could potentially benefit the millions of children affected by pathogen-induced diarrhea in developing countries.

When premature infants are born, their aseptic guts are rapidly colonized by microbes from the environment. If their gut is not sufficiently mature, the rapid microbial colonization leads to inappropriate excessive inflammation. Without control of the innate immune response that comes with maturity, the tissue develops an inflammatory disease called necrotizing enterocolitis. The lack of suitable model system limits our ability to study the etiology of this inflammatory disease of the premature infant gut.

We have developed a number of human and animal models during the past five years to study bacterial epithelial crosstalk that is vital for the well-being of all mammals. Using various cellular, molecular, genetic and proteomic approaches, mechanisms of bacteria-epithelial communication are investigated to identify unique interactions between the host intestinal mucosa and bacteria, including mutualistic symbionts, pathogens and probiotics.

Dr. Nanthakumar's Advisees/Trainees: