Modulating Early Life Microbiome Through Dietary Intervention in Crohn's Disease

The study design is a three-arm, prospective, pre-post intervention trial. Crohn's Disease
(CD) patients at 27-29 weeks of pregnancy will self-select to Arm 1 or Arm 2. Controls will
be in Arm 3.

1. Arm 1 (diet-CD): 8-10 weeks of dietary intervention (n=66)

2. Arm 2 (no-diet-CD): usual diet with no diet intervention (n=66)

3. Arm 3 (no-diet-control): unaffected controls at the same gestational stage will follow
their usual diet and no intervention (n=66).

The goal of this study is to prospectively test the hypothesis that a non-invasive dietary
intervention during the last trimester of pregnancy could beneficially shift the microbiome
of CD patients and their babies, hereby promoting a healthier immune system during a critical
time of the immune system development. Particularly, the study team will test whether
favorable diet-driven changes in the microbiome can lead to a reduced risk of postpartum
relapse and lower gut inflammation in the offspring.

Stool, saliva, breast milk and umbilical cord blood samples will be collected, and
questionnaires administered. Self-selected participants to Arm 1 will adopt a specified diet,
which will be adapted to address specific needs of third trimester pregnancy without
compromising the diet principles. Subjects will receive nutritional counseling and training,
and compliance to dietary recommendations will be recorded.

Analysis will be performed to correlate dietary change and assessed changes in quality of
life with microbial composition in the gut and with circulating markers of inflammation in
moms. The study team will also compare the effect of diet vs. non-diet on babies' microbiome
and the impact of the early life microbiome in levels of inflammatory markers after 1-year of
partum.

This study will help better understand the origin of the initial bacterial colonization in
high-risk babies, providing potential intervention targets for primary CD prevention. The
study team will also generate an extensive collection of serial samples and longitudinal
clinical data, including identification of specific dietary components correlated with
certain functional and quantitative bacterial patterns for future investigations. This study
will help create new opportunities to foster a healthy microbiome in high risk babies of
microbiome and immunity-mediated diseases, thereby hopefully reducing their risk later in
life.

Inclusion Criteria:

- Capacity to sign informed consent

- At least 18 years old

- Singleton pregnancy of less than 27-29 weeks gestation

- English-speaking

Exclusion Criteria:

- Inability to provide informed consent

- HIV/AIDS

- Multi-fetus pregnancy

- Fetal chromosomal or structural abnormalities

- Active infection (including chorioamnionitis or sepsis)

- Alcohol use disorder

- Diagnosis of diabetes, renal disease, or intrauterine growth restriction

- Non-English speaking

- Active perianal or extraintestinal disease

- Antibiotic or steroid treatment at recruitment

- Scheduled cesarean section prior to gestational week 37