VEO-IBD is a rare disease with an estimated worldwide prevalence of 14/100 000 and incidence of 4.3 per 100,000 children. Many VEO-IBD patients have a strong family history of the disease and approximately 25% of these patients have an underlying genetic defect causing immunodeficiency.

Due to the rarity and diversity of the disease VEO-IBD patients have not been well studied so far. Therefore, there remains a need for further research to obtain a better understanding of its causes, treatments, and the underlying disease processes.  

The human body, and specifically the human gut, is home to trillions of microbes including bacteria, viruses and fungi. We refer to those normal, commensal inhabitants as the “microbiome”.

The microbiome is important to maintaining some aspects of human health. Microbes begin colonizing the human gut right after birth and undergos a highly dynamic period until it reaches an adult-like configuration around three years of age. This process of microbiome maturation is not well understood, but can be crucial for the establishment of a “healthy” microbiome. Microbes participate in many complex physiological and immunological processes, like digesting food and acquiring nutrients, excluding pathogens, and directing immune system development. 

In order to take advantage of these benefits without being overrun, the immune system must maintain a delicate balance with its microbial residents. However,  if this balance is preturbed, diseases like diabetes, obesity, asthma, and inflammatory bowel disease can arise.

Adult IBD can have many causes, but in some cases, severe inflammation and injury can occur when the immune system has a strong response to the microbes that normally live in our gut. The specific composition of microbes living in our gut may play a role in determining how likely these inappropriate immune responses are to occur. 

Research has observed that inflammatory bowel disease in both adult and pediatric patients is associated with lower microbial diversity. In addition, some bacteria have been shown to be more beneficial to a healthy gut, and might be lost in disease. On the other hand, some bacteria that were more commonly found in IBD patients may possibly drive inflammation through degradation of the protective mucus layer covering the gut epithelium or through the production of harmful metabolites.

Very little is currently understood about the role that the gut microbiome plays in the development of very early-onset inflammatory bowel disease. In this study, we will characterize the community composition and stability of the gut and oral microbiome in VEO-IBD patients over time, as well as the human immune response during IBD flares and remission.

This will help us better understand the role that microbes play in disease development and severity, as well as how inflammation can change the nature of host-microbe interactions in the gut. In addition, we hope to identify microbial signatures and/or novel immune biomarkers that can predict IBD flares and/or responsiveness to various therapeutic interventions. These investigations may lead to more relaible diagnostic tests and enable earlier, patient-specific interventions that reflect the best available treatment options. 

• You are/your child is invited to participate in our research study of the role of the gut microbiome in very-early-onset inflammatory bowel disease:

- If your child has been diagnosed with IBD before the age of 6 years

- You live in the San Francisco Bay Area

If you or your child chooses to participate in this study, our research study staff may ask you to:

1. Assist your treating physician in the completion of a one-time initial subject profile about general subject information, subject health profile, family health history, and treatment history.
2. VEO-IDB patients will be asked to collect a series of "baseline" stool and oral samples at home on three consecutive days each month for six months. Parents and healthy siblings may also be asked to collect daily samples. 
3. If the VEO-IBD patient experiences a change in disease (either remission to flare or flare to remission) OR a change of medication, we ask that an additional set of "perturbation" samples be collected for 7 consecutive days. Otherwise, the collection protocol is the same as for the "baseline" samples.
4. One complete sample set (either "baseline" or "perturbation") includes a stool tube, a stool swab stored in preservative, and a tongue swab. In addition to these samples, a brief questionnaire on the subject's health, nutrition, and medications should be filled out. Detailed sample collection instructions and all sampling materials will be provided by the research study staff. Samples should be stored in a provided insulated bag inside your home freezer until you are ready to ship them to study personnel. A daily sample collection should take no longer than 15 minutes.
5. In some cases, we may ask you for additional testing, such as genome sequencing, gene expression profiling, assessment of the immunological response, assessment of bacterial DNA in your blood sample.

Your participation in this study is entirely voluntary. Your participation is for research only and you will not gain any medical benefit from participating in the study. If you wish to participate in this study, you must sign a consent form. You can decide to participate now, but withdraw your consent at any later time and stop your participation immediately. Your decision to stop participation will not have any negative effect on you or your medical care.  If samples that you have provided for the study have already been stored in an anonymous fashion (so they can not be linked to you), and you decide to stop participating in the study, it will not be possible to stop further research on the samples you have already provided.

If you would like to learn more about this study or are interested in participating, click the link to the right to be contacted by the VEO-IBD and the Microbiome research team or email us directly at veoibd-microbiome@stanford.edu.