We are particularly interested in understanding these overarching questions in our lab:
How does the community of viruses in the infant gut develop?
Using next generation sequencing we have shown that in contrast to the stable microbiome and virome observed in adults, the infant microbiome and virome is highly dynamic during early childhood. We then demonstrated that only 15% of the viruses in an infant’s gut were also in their mother’s gut suggesting that infant gut viruses are likely from other sources. We are currently conducting an ongoing prospective longitudinal birth cohort study to define the contribution of the hospital and home environment on the infant gut microbiome and virome.
What is the role of the infant gut virome and bacterial microbiome in the development of disease?
Childhood growth
Environmental enteric dysfunction (EED) is an inflammatory process that is endemic in children in low and middle-income countries which leads to stunting (poor linear growth). Stunting is associated with ~20% of all-cause deaths before age 5. EED and, by extension, stunting are thought to have microbial origins. In a longitudinal cohort of Malawian children with environmental enteric dysfunction, we found bacterial and phage signatures which distinguished children with good vs. poor growth velocities.
Necrotizing enterocolitis
Necrotizing enterocolitis (NEC) is a serious, sudden, and often fatal complication of preterm birth. NEC is associated with gut bacterial microbiome alterations. However, previously little was known about the role of the gut virome in NEC. In a longitudinal cohort of premature infants, we found bacterial and viral perturbations which preceded the sudden onset of NEC. We observed a convergence towards reduced viral beta diversity in the 10 days before NEC onset, which was driven by specific viral signatures and accompanied by specific viral-bacterial interactions.
This suggests, that the accrual of NEC-associated viruses may be a distinctive feature of the pre-NEC state.
Diarrhea
In a multi-site comparison of the stool viromes of children with diarrhea across economically diverse and geographic distinct sites, we reported that viromes from children in a rural resource poor setting contain more viral families per sample than viromes from a westernized urban setting. Additionally, we discovered novel astroviruses (MLB2, MLB3, VA2, VA3, VA4, VA5) as well as novel picornaviruses (klassevirus and cosavirus E-1) in pediatric diarrhea samples.
How can we improve our understanding of celiac disease in order to ultimately improve the lives of our patients with celiac disease?
Celiac disease (CD) is an immune mediated enteropathy caused by ingestion of gluten in genetically susceptible individuals. A subset of patients have positive celiac serology, but have normal duodenal villous architecture (potential celiac disease). We performed a retrospective study of children at our center to better understand the subset of children with potential celiac disease who progress to celiac disease. We found that 28% of children with positive serology and initially normal biopsy went on to have biopsy confirmed CD. We are particularly interested in this progression of disease, as we may learn valuable insights into the mechanisms underlying CD.
Ongoing projects
Maternal Offspring Microbiome (MOM) Study
We all have microbial communities in and on our bodies that are extremely important for health and development. From previous research, we know that these microbes are picked up very early in life and that they help babies digest food and develop healthy immune systems. We also know that an abnormal microbiome can be associated with increased risk for conditions like asthma, allergies, infections, and obesity.
The MOM study is a longitudinal, observational study that follows participating families for approximately one year to identify the origins of infants’ microbiomes and microbial transmission dynamics among household members and the environment. The central hypothesis of this study is that the term infant bacterial microbiome and virome are acquired from post-natal environmental exposures and persist throughout infancy.
Pediatric Celiac Disease Repository
We are creating a repository of both clinical data and biological samples of pediatric patients seen at St. Louis Children’s Hospital with suspected and confirmed celiac disease. This repository will provide a rich resource to better understand the natural disease process and to ask questions regarding the many currently unanswered questions about celiac disease.