Diabetes, Insulin, Gut, Enteric Supplementation Trial (DIGEST)

Effects of a Kefir Intervention in Pregnancy on Glucose, Insulin, Gestational Diabetes Mellitus, and the Gut Microbiome and Metabolites: A Randomized Controlled Trial

Pregnancy is a critical window for metabolic health, and early changes in blood sugar regulation can increase the risk of gestational diabetes mellitus (GDM), which affects both maternal and infant health. At the same time, the maternal gut microbiome changes throughout pregnancy and may play a role in glucose metabolism and insulin resistance. Kefir, a fermented milk drink containing beneficial bacteria and yeasts, may be a simple dietary strategy to support metabolic health during pregnancy, but its role in preventing GDM has not been well studied.

This study will test whether drinking kefir daily from mid-pregnancy until routine GDM screening can improve glucose and insulin regulation, reduce the incidence of GDM, and modulate the maternal gut microbiome and metabolites, among other outcomes.

Pregnant individuals will be randomly assigned to either a kefir group or a control group receiving usual prenatal care. Researchers will collect blood glucose and insulin measures, dietary information, stool samples, and body composition data across pregnancy and postpartum to evaluate metabolic and microbiome-related changes.

As one of the first studies to examine kefir as an early pregnancy intervention for GDM prevention, this study will help clarify whether a practical, food-based approach can improve maternal metabolic health. The findings may support future nutrition strategies aimed at reducing GDM risk and improving pregnancy outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Blood Glucose; Gut Microbiome; Gestational Diabetes Mellitus (GDM); Insulin Resistance, Diabetes; Gut Metabolites
• Intervention / Treatment: Dietary supplement: Kefir

Detailed Description

Pregnancy is characterized by progressive metabolic and hormonal changes, including increasing insulin resistance, particularly in the second trimester. At the same time, the maternal gut microbiome undergoes substantial shifts across gestation and may contribute to glucose metabolism, insulin resistance, and inflammation. Dietary strategies that can favorably influence the gut microbiome and metabolic health during pregnancy may represent a promising approach to reduce GDM risk. Kefir, a fermented dairy beverage containing a complex consortium of beneficial bacteria and yeasts, has shown potential for improving glycemic control and modulating the gut microbiome in non-pregnant populations, but its preventive role for GDM has not been well established.

The primary aims of this study are to determine whether daily kefir consumption initiated in mid-pregnancy can improve maternal glucose and insulin regulation. Secondary aims will examine whether kefir consumption reduces the incidence of GDM, beneficially modulates maternal gut microbiome and metabolite profiles, and alters postpartum health measures such as breastmilk composition and infant anthropometrics.

This randomized controlled trial in the PEADS Lab at the University of New Brunswick will assign pregnant participants to either a daily kefir intervention group or a control group receiving usual prenatal care. Participants in the intervention group will consume 250 mL of kefir daily beginning at approximately 14 weeks' gestation and continuing until the routine GDM screening window at 26-28 weeks' gestation. Those in the control group will continue with their usual care and habitual diet, but will be asked not to consume kefir for the duration of the study. Participants will attend study visits across pregnancy and postpartum, during which researchers will collect dietary recalls, anthropometric and body composition measurements, blood pressure, and stool and breastmilk samples. Fasted clinical bloodwork will be used to assess glucose and insulin-related outcomes, including screening for GDM.

The primary outcomes are between-group differences in maternal glycemic and insulinemic measures. Secondary outcomes include the incidence of GDM, changes in gut microbial diversity, composition, and metabolites such as short-chain fatty acid concentrations, maternal body composition, breastmilk composition, and infant anthropometrics. Assessments will occur at baseline (~14 weeks gestation), at the GDM screening windows (18-20 weeks for high-risk and 26-28 weeks for low-risk), and one month postpartum.

Pregnancy represents a critical opportunity for early prevention of metabolic complications that can affect lifelong maternal and child health. This study is the first to evaluate kefir as a practical, food-based intervention for GDM prevention, while also exploring the role of the gut microbiome as a potential modifiable mechanism. By integrating clinical, dietary, and microbiome data, this trial will help generate evidence to support accessible nutrition strategies that may improve pregnancy outcomes and inform future maternal health recommendations.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maryam Kebbe, PhD, CLC; Phone Number: 15064516872; Email: maryam.kebbe@unb.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant individual with a singleton pregnancy
• 19 years and older of age
• Gestational age 14,3 weeks or less at enrolment
• Able and willing to attend four in-person study visits at the PEADS Laboratory: baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, and 1 month postpartum
• Willing and able to comply with study group assignment, including daily consumption of 250 mL of kefir if assigned to the intervention group
• Willing to avoid kefir consumption until completion of the 26-28-week study visit if assigned to the control group
• Willing to provide required biological and clinical samples, including stool samples and glucose/insulin data, according to the study protocol
• No probiotic, prebiotic, synbiotic, or antibiotic use during the first trimester or at enrollment
• Not currently consuming probiotic, prebiotic, synbiotic, or antiobiotic supplements
• Willing to avoid probiotic, prebiotic, and synbiotic supplements until completion of the 26-28-week study visit.
• Does not engage in regular moderate-to-vigorous physical activity
• No recent or active infectious illness or significant gastrointestinal symptoms, including diarrhea or constipation in the first trimester of pregnancy.
• No history of bariatric surgery
• Able to communicate in English or French
• Currently living in Fredericton, New Brunswick, and not planning to relocate before the 1-month postpartum visit

Exclusion Criteria:

• Pre-existing metabolic disease affecting glucose regulation, including type 1 diabetes or type 2 diabetes
• Current use or first trimester use of medications known to alter glucose metabolism, such as metformin or semaglutide
• Gastrointestinal or inflammatory disease, including Crohn's disease, ulcerative colitis, celiac disease, or diagnosed irritable bowel syndrome
• Allergy, intolerance, or other contraindication to dairy or components of kefir

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daily Kefir Intake; Participants assigned to this group will consume 250 mL of kefir daily beginning at approximately 14 weeks' gestation through the routine GDM screening window at 26-28 weeks' gestation. Participants will otherwise continue their usual prenatal care and habitual diet.	Dietary supplement: Kefir; Kefir is a fermented dairy beverage containing a complex host of live bacteria and yeasts. In this study, participants assigned to the intervention group will consume 250 mL of kefir daily from approximately 14 weeks' gestation until the routine GDM screening window at 26-28 weeks' gestation. Participants will otherwise continue their usual prenatal care and habitual diet.
No Intervention: Control Group; Participants assigned to this group will continue their usual prenatal care and habitual diet beginning at approximately 14 weeks' gestation through the routine GDM screening window at 26-28 weeks' gestation. Participants will not consume the study kefir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Fasting Glucose Concentrations	Between-group difference in maternal fasting glucose concentrations measured at baseline (14 weeks' gestation) and during pregnancy via glucose challenge testing conducted within the respective screening window (18-20 weeks' gestation for high-risk or 24-28 weeks' gestation for high-risk and/or low-risk).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation
Maternal hbA1c Concentrations	Between-group difference in maternal hbA1c concentrations measured at baseline (14 weeks' gestation) and during pregnancy conducted within the respective screening window (18-20 weeks' gestation for high-risk or 24-28 weeks' gestation for high-risk and/or low-risk).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation
Maternal Fasting Insulin Concentrations	Between-group difference in maternal fasting insulin concentrations measured during pregnancy at the respective screening window (18-20 weeks' gestation for high-risk or 24-28 weeks' gestation for high-risk and/or low-risk).	18-20 weeks' gestation, 26-28 weeks' gestation
Maternal Insulin Area Under the Curve	Between-group difference in maternal insulin area under the curve measured during pregnancy at the respective screening window (18-20 weeks' gestation for high-risk or 24-28 weeks' gestation for high-risk and/or low-risk).	18-20 weeks' gestation, 26-28 weeks' gestation
Maternal Whole-Body Insulin Sensitivity	Between-group difference in maternal whole-body insulin sensitivity measured during pregnancy at the respective screening window (18-20 weeks' gestation for high-risk or 24-28 weeks' gestation for high-risk and/or low-risk).	18-20 weeks' gestation, 26-28 weeks' gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiome Diversity and Composition	Gut microbiome diversity and taxa will be assessed using metagenomic sequencing of stool samples collected from participants. Alpha diversity metrics (e.g., Shannon index, Chao1) and beta diversity metrics (Bray-Curtis dissimilarity) will quantify within- and between-sample microbial diversity. Taxonomic composition at phylum, family, and genus levels will be examined.	At baseline, 18-20 weeks' gestation, and 26-28 weeks' gestation
Gut Microbiome Metabolites	Microbial metabolite profiles relevant to inflammation and metabolic regulation such as short-chain fatty acids will be examined.	At baseline, 18-20 weeks' gestation, and 26-28 weeks' gestation
Maternal Weight	Maternal weight will be measured at each study visit.	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Maternal Height	Maternal height will be measured at baseline.	Baseline
Maternal Body Composition (BOD POD)	Maternal body composition will be assessed at each visit using air-displacement plethysmography to estimate fat mass and fat-free mass.	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Maternal Blood Pressure	Maternal blood pressure will be measured to provide additional information on maternal cardiovascular and metabolic health.	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Maternal Breastmilk Composition (Miris HMA)	Breastmilk will be collected 1 month postpartum.	1 month postpartum
Infant Length	Infant length will be assessed using standardized procedures 1 month postpartum.	1 month postpartum
Infant Weight	Infant weight will be assessed using standardized procedures 1 month postpartum.	1 month postpartum
Infant Head and Abdominal Circumferences	Infant circumferences will be assessed using standardized procedures 1 month postpartum.	1 month postpartum
Infant Body Composition	Infant body composition will be assessed using air-displacement plethysmography 1 month postpartum.	1 month postpartum
Dietary intake	Participants will complete the Automated Self-Administered 24-hour dietary assessment tool (ASA-24) at two time points (one weekday and one weekend).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Pregnancy Physical Activity Questionnaire	Participants will complete the Pregnancy Physical Activity Questionnaire (PPAQ).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Postpartum Physical Activity Questionnaire	Participants will complete the Postpartum Physical Activity Questionnaire.	1 month postpartum
Edinburgh Postnatal Depression Scale	Participants will complete the Edinburgh Postnatal Depression Scale (EPDS).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Anxiety subscale of the Symptom Checklist-90	Participants will complete the Anxiety subscale of the Symptom Checklist-90 (SCL-90).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum
Weight Control Strategies Scale	Participants will complete the Weight Control Strategies Scale (WCSS).	Baseline, 18-20 weeks' gestation, 26-28 weeks' gestation, 1 month postpartum

Collaborators and Investigators

• Sponsor: University of New Brunswick
• Investigators: Principal Investigator: Maryam Kebbe, PhD, CLC, University of New Brunswick

Publications and helpful links

General Publications

• Zhu Y, Zhang C. Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective. Curr Diab Rep. 2016 Jan;16(1):7. doi: 10.1007/s11892-015-0699-x.
• Salari A, Ghodrat S, Gheflati A, Jarahi L, Hashemi M, Afshari A. Effect of kefir beverage consumption on glycemic control: A systematic review and meta-analysis of randomized controlled clinical trials. Complement Ther Clin Pract. 2021 Aug;44:101443. doi: 10.1016/j.ctcp.2021.101443. Epub 2021 Jul 13.
• van Raaij JM, Peek ME, Vermaat-Miedema SH, Schonk CM, Hautvast JG. New equations for estimating body fat mass in pregnancy from body density or total body water. Am J Clin Nutr. 1988 Jul;48(1):24-9. doi: 10.1093/ajcn/48.1.24.
• Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The Pathophysiology of Gestational Diabetes Mellitus. Int J Mol Sci. 2018 Oct 26;19(11):3342. doi: 10.3390/ijms19113342.
• Pakmehr A, Ejtahed HS, Shirzad N, Hemmatabadi M, Farhat S, Larijani B. Preventive effect of probiotics supplementation on occurrence of gestational diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Front Med (Lausanne). 2022 Dec 1;9:1031915. doi: 10.3389/fmed.2022.1031915. eCollection 2022.
• O'Malley EG, Reynolds CME, O'Kelly R, McMahon L, Sheehan SR, Turner MJ. The diagnosis of gestational diabetes mellitus (GDM) using a 75 g oral glucose tolerance test: A prospective observational study. Diabetes Res Clin Pract. 2020 May;163:108144. doi: 10.1016/j.diabres.2020.108144. Epub 2020 Apr 13.
• Nakshine VS, Jogdand SD. A Comprehensive Review of Gestational Diabetes Mellitus: Impacts on Maternal Health, Fetal Development, Childhood Outcomes, and Long-Term Treatment Strategies. Cureus. 2023 Oct 23;15(10):e47500. doi: 10.7759/cureus.47500. eCollection 2023 Oct.
• Johns EC, Denison FC, Norman JE, Reynolds RM. Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab. 2018 Nov;29(11):743-754. doi: 10.1016/j.tem.2018.09.004. Epub 2018 Oct 5.
• Hivert MF, Backman H, Benhalima K, Catalano P, Desoye G, Immanuel J, McKinlay CJD, Meek CL, Nolan CJ, Ram U, Sweeting A, Simmons D, Jawerbaum A. Pathophysiology from preconception, during pregnancy, and beyond. Lancet. 2024 Jul 13;404(10448):158-174. doi: 10.1016/S0140-6736(24)00827-4. Epub 2024 Jun 20.
• Hamsho M, Hawari R, Yesil Z, Dakhel Z, Dursun Saydam D, Terzi M, Ranneh Y. Effect of different kefir dosages on inflammation status, metabolic profile, and anthropometric measurements in adults: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2026 May;36(5):104364. doi: 10.1016/j.numecd.2025.104364. Epub 2025 Sep 11.
• Fisher PM, Sutherland HW, Bewsher PD. The insulin response to glucose infusion in normal human pregnancy. Diabetologia. 1980 Jul;19(1):15-20. doi: 10.1007/BF00258304.
• Crusell MKW, Hansen TH, Nielsen T, Allin KH, Ruhlemann MC, Damm P, Vestergaard H, Rorbye C, Jorgensen NR, Christiansen OB, Heinsen FA, Franke A, Hansen T, Lauenborg J, Pedersen O. Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum. Microbiome. 2018 May 15;6(1):89. doi: 10.1186/s40168-018-0472-x.
• Choi Y, Keum GB, Kang J, Doo H, Kwak J, Kim H, Chae Y, Lee S, Yang H, Kim S, Sun X, Kim HB, Yoo SJ. Evaluation of kefir consumption on gut microbial diversity in a healthy young population using full-length 16S rRNA sequencing. Front Microbiol. 2025 May 21;16:1587831. doi: 10.3389/fmicb.2025.1587831. eCollection 2025.
• Bianchi C, de Gennaro G, Romano M, Battini L, Aragona M, Corfini M, Del Prato S, Bertolotto A. Early vs. standard screening and treatment of gestational diabetes in high-risk women - An attempt to determine relative advantages and disadvantages. Nutr Metab Cardiovasc Dis. 2019 Jun;29(6):598-603. doi: 10.1016/j.numecd.2019.02.007. Epub 2019 Mar 1.
• Asgharian H, Homayouni-Rad A, Mirghafourvand M, Mohammad-Alizadeh-Charandabi S. Effect of probiotic yoghurt on plasma glucose in overweight and obese pregnant women: a randomized controlled clinical trial. Eur J Nutr. 2020 Feb;59(1):205-215. doi: 10.1007/s00394-019-01900-1. Epub 2019 May 8.
• Song S, Duo Y, Zhang Y, Qiao X, Xu J, Zhang J, Peng Z, Chen Y, Nie X, Sun Q, Yang X, Wang A, Sun W, Fu Y, Dong Y, Lu Z, Yuan T, Zhao W. The Predictive Ability of Hepatic Steatosis Index for Gestational Diabetes Mellitus and Large for Gestational Age Infant Compared with Other Noninvasive Indices Among Chinese Pregnancies: A Preliminary Double-center Cohort Study. Diabetes Metab Syndr Obes. 2021 Dec 16;14:4791-4800. doi: 10.2147/DMSO.S335364. eCollection 2021.
• Staynova R, Vasileva E, Yanachkova V. Gestational diabetes mellitus: a growing economic concern. Folia Med (Plovdiv). 2022 Oct 31;64(5):725-732. doi: 10.3897/folmed.64.e65693.
• Edwards SM, Cunningham SA, Dunlop AL, Corwin EJ. The Maternal Gut Microbiome During Pregnancy. MCN Am J Matern Child Nurs. 2017 Nov/Dec;42(6):310-317. doi: 10.1097/NMC.0000000000000372.
• Arum P, Kdekian A, Lutgers HL, Gordijn SJ, Veenstra MK, Sietzema M, Kruit JK, van der Beek EM. Early pregnancy meal tolerance test responses and their association with later insulin sensitivity in overweight and obese women: an exploratory analysis. Front Endocrinol (Lausanne). 2026 Jan 28;17:1763137. doi: 10.3389/fendo.2026.1763137. eCollection 2026.
• Kishimoto M, Tamaru S, Odawara M. Risk factors for gestational diabetes mellitus and postpartum glucose intolerance: a retrospective study from a hospital specializing in infertility treatment. Sci Rep. 2025 Nov 12;15(1):39731. doi: 10.1038/s41598-025-23404-1.
• Moon JH, Jang HC. Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications. Diabetes Metab J. 2022 Jan;46(1):3-14. doi: 10.4093/dmj.2021.0335. Epub 2022 Jan 27.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Insulin; Pregnancy; Probiotics; Glucose; Gut microbiome; Gestational diabetes mellitus; Kefir; Gut metabolites
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Hyperinsulinism; Nutritional and Metabolic Diseases; Diabetes, Gestational; Diabetes Mellitus; Insulin Resistance; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Beverages; Cultured Milk Products; Fermented Foods; Dairy Products; Milk; Fermented Beverages; Kefir
• Other Study ID Numbers: 2026-633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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