The Effects of Omega-3 PUFAs on the Infant Microbiome and Immunity

The Effects of Omega-3 Polyunsaturated Fatty Acids on the Infant Microbiome and Immunity

Prenatal supplementation with fish oil, rich in omega-3 polyunsaturated fatty acids, is widely recommended in Canada. The aim of this observational, prospective cohort study is to determine the effects of maternal fish oil supplements on the development of their infants' gut microbiota and immunity.

Study Overview

• Status: Completed
• Conditions: Microbial Colonization; Infant Development
• Intervention / Treatment: Dietary supplement: Fish oil supplements

Detailed Description

During infancy, the gastrointestinal tract is colonized with microbiota, a community of microorganisms, which play a significant role in the development, regulation, and maintenance of immune functions. Fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), are thought to be anti-inflammatory and consequently may increase susceptibility to infection by hindering their body's ability to produce an adequate inflammatory response in defense against infectious disease. Currently, women in Canada are supplementing their diets with n-3 PUFA during gestation and lactation despite their being conflicting clinical evidence regarding the beneficial effects on infant development. It is currently unknown how maternal fish oil supplementation impacts the offspring's gut microbiota and immune functions. Considering that diet influences microbiota and maternal microbiota is passed from mother to infant, the investigators hypothesize that maternal fish oil supplementation will affect the participants' infant gut microbiota and immunity.

This study will evaluate the effects of postnatal n-3 PUFA supplementation in breast milk on the fecal microbiome in infants over a six-month period. The investigators will analyze the fecal microbiome of infants born to mothers in the fish oil and non-fish oil groups via next generation sequencing. As short-chain fatty acids (SCFA) are produced by gut bacteria and affect immunity, the investigators will analyze SCFA in stool through gas chromatography. Markers of inflammation like fecal calprotectin and sIgA in stool samples will also be identified.

• Study Type: Observational
• Enrollment (Actual): 109

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Healthy women in the Okanagan Valley who predominantly breastfeed their healthy, full-term infants while self-administering fish oil supplements or not.

Description

Inclusion Criteria:

• All mothers of infants in the Okanagan Valley are invited to participate in the study between the first day of delivery to until solid food is introduced into the infant's diet.
• Healthy, full-term infants, who are predominantly breastfed by mothers who are or are not supplementing with fish oil. Mothers must also be healthy, i.e., asymptomatic and with no clinical indication of disease.
• To remain within the inclusion criteria for this study, participants will be expected to be consistent (i.e. maintain the same type and amount of omega-3 PUFA intake or no intake) with whichever supplementation group they have decided to join for the entirety of the breast milk and infant stool donation period. In other words, the investigators will be asking the participants not to switch from one group to another which would happen by changing their omega-3 PUFA supplementation patterns.

Exclusion Criteria:

• Any infants who are ingesting juice or solid foods as part of their regular diet will be excluded from the study.
• Any infants who are clinically ill (fever, contagious diseases, or active diarrhea) will be excluded from the study.
• Any participants who decide to drastically change their omega-3 PUFA supplementation intake patterns (i.e. causing them to switch between study groups) will result in all subsequent samples to be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fish oil group; Women who chose to supplement with fish oil, rich in omega-3 polyunsaturated fatty acids, during gestation or lactation.	Dietary supplement: Fish oil supplements; Women who chose to supplement with fish oil during gestation or lactation.
No fish oil group; Women who chose not to supplement with fish oil during gestation or lactation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in infant fecal microbiota of the two groups.	Fecal microbiota will be measured by examining microbial taxa from infant stool every month from birth until 6-months of age or until solids are introduced.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in infant short-chain fatty acid production of the two groups.	Changes in short-chain fatty acid production will be analyzed in infant stool through gas chromatography.	6 months
Changes in infant IgA in shed intestinal epithelial cells of the two groups.	We will examine the effects of fish oil on immunity by measuring fecal IgA concentrations using ELISA	6 months
Changes in infant cytokines in shed intestinal epithelial cells of the two groups.	We will examine the effects of fish oil on immunity by measuring fecal cytokines (TNF-a, IFN-y, IL-17) using real time PCR.	6 months
Compare occurrences of sickness and incidences of disease between the two groups.	Any incidences of disease in the infants will be closely monitored for the first 2 years of their lives.	2 years
Changes in breast milk IgA composition of the two groups.	Immune markers such as sIgA will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)	6 months
Changes in breast milk cytokine composition of the two groups.	Immune markers such cytokines will be measured in breast milk using an addressable laser bead immunoassay (ALBIA)	6 months
Changes in breast milk lipid composition of the two groups.	Breast milk lipid concentrations will be analyzed using short-chain fatty acids	6 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: Principal Investigator: Deanna L Gibson, Ph.D., University of British Columbia

Publications and helpful links

General Publications

• Quin C, Estaki M, Vollman DM, Barnett JA, Gill SK, Gibson DL. Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison. Sci Rep. 2018 May 29;8(1):8283. doi: 10.1038/s41598-018-26423-3.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: September 25, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 29, 2017

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: H13-02523

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Infant stool microbial data will be made open access upon publishing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No