Celiac Disease Genomic Environmental Microbiome and Metabolomic Study

The CDGEMM study will address genomic, environmental, microbiome, and metabolomic factors that could affect the development of CD.

Genomic: The investigators will study children who have a first degree relative with celiac disease so that we can understand how their genes may contribute to whether they develop CD or not. Scientists and doctors are already aware of one group of genes, called the HLA DQ2 and DQ8 genes, which are involved in the development of CD. These genes are necessary for development of CD, but cannot alone predict who will develop the disease. The investigators hope that the CDGEMM study will help to not only learn more about these specific genes, but also identify other genes that could make it easier to predict who will develop CD.

Environmental: When infants enroll, the investigators will record information about their environment including whether they were born vaginally or by Cesarean section and whether they were given antibiotics. Over time, the investigators will also consider other parts of the infant's medical history including feeding modality (breastfeeding versus formula feeding), illnesses, infections, and growth to understand if any of this information is related to CD development. Since the investigators will follow infants until they reach 5 years of age, the investigators will update this information every six months to understand how changes might affect if the child develops CD or not.

Microbiome: Our gut, compromised of the small and large intestine, contains many types of bacteria. These bacteria that live in the gut normally help to break down and digest food, provide our bodies with energy, and make vitamins that our bodies need. This diverse community of bacteria is called the gut microbiome. A main goal of the CDGEMM study is to understand how the microbiome is affected by other factors, like foods or antibiotic drugs, and how this may affect the development of CD. It is possible that learning about the types of bacteria living in the gut before and after disease development may help us predict who will develop CD before it happens.

Metabolomic: The processes that occur in our gut, such as the digestion of foods and production of vitamins, create products that are called metabolites. The specific metabolites that we produce differ from person to person and depend on many factors, including the genes that we have, the members of the gut microbiome, and the foods that we eat. We will study the infant's unique metabolomic profile (metabolites that the infant produces) to understand if there is a specific profile associated with CD.

• Change in gut permeability measured by serum zonulin levels and loss of gluten tolerance measured by increased expression of pro-inflammatory cytokines and appearance of anti-tTg antibodies. [Time frame: Every six months until age 3. Every year thereafter until age 5.]