Department of Pediatrics
Department of Pediatrics
The Department of Pediatrics

Gastroenterology - Research

Our division advances the treatment of pediatric gastrointestinal and liver disorders through excellent patient care, research and education.


Gastroenterology Research

Each member of the division is actively pursuing or has a record of aggressive pursuit of an area of clinical research:  Dr. Navarro – inflammatory bowel disease and nutrition; gastrointestinal function and its relationship to behavior in autism; citrulline metabolism and infant nutrition in short bowel syndrome.  Dr. Gleason – Vitamin D metabolism in the intestine and liver and its relationship to health and disease.  Dr. Imseis – functional dyspepsia and response to medical therapy; Hirschsprung’s disease.  Dr. Rhoads – infantile colic, gut inflammation, response to a probiotic (L. reuteri), and relationship to the colonic microbiota.  Two of our members are active in basic sciences research:  Dr. Liu and Dr. Rhoads share a laboratory investigating toll-like receptor signaling in the intestine and its relationship to the inflammatory response in necrotizing enterocolitis (NEC), as well as anti- and pro-inflammatory signaling by probiotics, which might improve outcomes in NEC. 

Our fellows are required to take the courses offered by the Center for Clinical and Translational Research (CCTR), headed by Dr. Jon Tyson.  Our members are also active participants in the Baylor-U.T.-M.D. Anderson Digestive Diseases Center, which sponsors a lecture series featuring internal and external expert speakers each week.

Clinical:  Ms. Nicole Fatheree, Dr. Mike Ferris (New Orleans Children’s Hospital), and I are studying how the fecal microbiota may contribute to infantile colic.  We have determined via molecular analysis of the stools of 36 infants that infants with colic have a significantly greater chance of having Klebsiella spp. in their stool when compared to normal infants; furthermore, they have elevated levels of fecal calprotectin (a neutrophil marker), indicating a greater degree of inflammation in the gastrointestinal tract.  After satisfying F.D.A. requirements for a Phase 1 Safety & Tolerability study in adult volunteers, we have N.I.H. funding to investigate the impact of Lactobacillus reuteri on:   colic symptoms; fecal microbiota and calprotectin; and circulating peripheral blood monocyte toll-like receptor (TLR) levels and cytokine production.  The study will be a double-masked, placebo-controlled trial in infants with colic. 

 

Basic:  Our lab focuses on mechanisms and treatment of neonatal diseases.  The two foci of our research are necrotizing enterocolitis (NEC) and infantile colic.  The NEC research focuses on the role of toll-like receptor signaling in the generation of inflammatory cytokines in experimental NEC.  We use a rat pup model of NEC and are determining the effects of 2 strains of Lactobacillus reuteri (LR) in modifying inflammatory signaling (Figure 1). In studies of intestinal epithelial cell monolayers, we are identifying the mechanism of protection from hypoxia-reoxygenation injury by two amino acids (Arginine and Citrulline).  Intestinal tight junction patency is measured by transepithelial electrical resistance, tight junction proteins, and inulin-FITC permeability. The colic studies focus on the role of the intestinal microbiota in producing intestinal inflammation in infants with colic.  A human treatment trial of LR is in progress.

In neonates lacking a well developed commensal flora, probiotic organisms may protect from NEC.  Anti-inflammatory response of probiotic Lactobacillus reuteri  is strain specific. Lactobacillus reuteri 17938 is TNF stimulatory strain, while Lactobacillus reuteri 6459 is TNF inhibitory strain. Proposed strain-specific mechanism of anti-inflammatory L. reuteri prevention of NEC via modulating TLR signaling in experimental newborn rat model.