Maternal & Offspring Microbiome Study

Study Overview
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Brief Summary
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The purpose of the study is to learn how different dietary interventions affect microbiota diversity in pregnant women and the transmission of microbiota to their infants during pregnancy, birth, and postpartum.

Detailed Description
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This research study aims to understand the relationship of dietary fiber, fermented foods, and the microbiome, specifically during pregnancy and postpartum. We know that the composition of the microbiome can have an important effect on our overall health, and a greater variety will confer more health benefits. Research suggests that maternal microbiota play an important role in the development of their offspring's microbiota during pregnancy, childbirth, and breastfeeding. The purpose of this study is to assess how diet impacts maternal microbiome during pregnancy and their infant's microbiome up to about two years postpartum. Potential pregnant participants will be recruited during their first trimester up to 22 weeks. After completion of the baseline visit and sample collection, they will be randomized to start a diet high in fiber, high in fermented foods, high in both fiber and fermented foods, or a usual care group. Participants will be asked to provide blood, stool, vaginal swab, and breast milk samples periodically throughout the study. Cord blood will be collected after childbirth, and infant blood from a heel stick will be collected twice. They will also be asked to fill out online questionnaires and perform dietary recalls with study diet assessors.

Official Title
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Effects of Fermented & Fiber-rich Foods on Maternal & Offspring Microbiome Study

Conditions
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Pregnancy Related, Microbiome, Immune Function, Inflammation

Intervention / Treatment
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* Behavioral: Fiber
* Behavioral: Fermented Foods


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age Singleton pregnancies Recruit during the first trimester and up to 22 weeks of pregnancy. Healthy subjects willing and able to provide blood, stool, vaginal swab, and breast milk samples. Must be able to provide signed and dated informed consent. Exclusion Criteria: Pre-pregnancy BMI greater than 40 Blood pressure SBP: > 160 mmHg -OR- DBP: > 90 mmHg Kidney disease Liver disease Anemia Symptomatic gallstones History of bariatric surgery Acute disease at time of enrollment (i.e. flu or gastroenteritis). May delay sampling until subject recovers. Chronic, clinically significant, unstable (unresolved, requiring on-going changes to medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality, as determined by medical history History of active uncontrolled gastrointestinal disorders or diseases including: Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis; Irritable bowel syndrome (IBS) (moderate-severe); Persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated) Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection. Surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time. Confirmed or suspected autoimmune disease Medications: Weight loss medications Regular high dose aspirin Regular use of prescription opiate pain medication If taken in the past 2 months: Systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular or oral) Corticosteroids (intravenous, intramuscular, oral, nasal or inhaled) Cytokines Methotrexate or immunosuppressive cytotoxic agents Diet & Lifestyle: Recent history of chronic excessive alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day; or > 14 drinks/week. Regular/frequent use of smoking or chewing tobacco, e-cigarettes, cigars or other nicotine-containing products Maternal chronic medical conditions: Pre-gestational diabetes (T1 or T2) History of gestational diabetes On medication that is an immune modulators or chronic steroid use Hyperemesis gravidarum Pregnancy history: Preterm birth Recurrent pregnancy loss

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber<br>Participants will be asked to increase their usual dietary fiber intake by 20 grams/day. | Behavioral: Fiber<br>* Additional 20 grams of fiber/day.<br>|
| Experimental: Fermented Foods<br>Participants will be asked to consume 6 servings of fermented foods per day. | Behavioral: Fermented Foods<br>* 6 servings of fermented foods/day<br>|
| Experimental: Fiber + Fermented Foods<br>Participants will be asked to increase their usual dietary fiber intake by 20 grams/day and to consume 6 servings of fermented foods per day. | Behavioral: Fiber<br>* Additional 20 grams of fiber/day.<br>Behavioral: Fermented Foods<br>* 6 servings of fermented foods/day<br>|
| No Intervention: Comparator<br>Participants will receive usual care for pregnancy and postpartum. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in total number of species detected in stool as a measure of infant microbiota diversity. | Difference in total number of species (ASVs - Amplicon Sequence Variants) detected in stool between the fiber, fermented, fiber + fermented and comparator arms at 1 month postpartum. | 1 month postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the total number of species detected in stool as a measure of maternal microbiota diversity. | Change in differences in total number of species (ASVs- Amplicon Sequence Variants) detected in stool from baseline to 36 weeks of pregnancy between fiber, fermented, fiber + fermented, and comparator arms. | Baseline and 36 weeks of pregnancy | 
| Change in the maternal inflammatory marker profile | Change in the differences in inflammatory markers (β-NGF, LIF-R, IL-12B, IL10, CASP-8, LAP TGF-β-1, CD6, CD5, MCP-2, IL6, CCL20, IL18, VEGFA, MMP-10, MCP-4, CCL4, CXCL10, CCL19, FGF-21) detected in blood samples from baseline to 36 weeks of pregnancy between fiber, fermented, fiber + fermented, and comparator arms. | Baseline and 36 weeks of pregnancy | 
| Characterize the infant inflammatory marker profile | Difference in amount of inflammatory markers (β-NGF, LIF-R, IL-12B, IL10, CASP-8, LAP TGF-β-1, CD6, CD5, MCP-2, IL6, CCL20, IL18, VEGFA, MMP-10, MCP-4, CCL4, CXCL10, CCL19, FGF-21) detected in heel stick blood between fiber, fermented, fiber + fermented, and comparator arms at 6 months postpartum. | 6 months postpartum | 
| Characterize the infant allergy marker profile | Difference in amount of allergy markers (skin prick testing) detected in heel stick blood between fiber, fermented, fiber + fermented, and comparator arms at 6 months postpartum. | 6 months postpartum | 
| Infant Growth | Difference in weight-for-length growth chart percentiles between fiber, fermented, fiber + fermented, and comparator arms at 18 months postpartum. | 18 months postpartum | 
| Maternal Weight | Differences in the number of participants who gained weight within the pregnancy weight gain recommendations between fiber, fermented, fiber + fermented, and comparator arms measured at 36 weeks. | 36 weeks of pregnancy | 
| Maternal systolic blood pressure | Change from baseline in systolic blood pressure at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal diastolic blood pressure | Change from baseline in diastolic blood pressure at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal LDL-cholesterol | Change from baseline in LDL cholesterol at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal HDL-cholesterol | Change from baseline in HDL cholesterol at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal triglycerides | Change from baseline in triglycerides at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal glucose | Change from baseline in glucose at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 
| Maternal fasting insulin | Change from baseline in fasting insulin at 36 weeks of pregnancy. | Baseline and 36 weeks of pregnancy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Microbiome, Immune function, Inflammation