Yogurt and GI Health Pilot Study

Sponsor

USDA, Western Human Nutrition Research Center (U.S. Fed)

Overall Status

Not yet recruiting

CT.gov ID

NCT05931471

Collaborator

(none)

Enrollment

Location

Arm

11.7

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research is to assess mucosal immune function responses in the gastrointestinal (GI) tract to twice-daily yogurt consumption. Previous research has shown that dairy yogurt intake can benefit gastrointestinal health. The current study will determine whether a dietary intervention with dairy yogurt will improve mucosal immunity and the gut microbiome.

Condition or Disease	Intervention/Treatment	Phase
Yogurt Intake Gastrointestinal Immune Function Gut Microbiome Gut Health	Other: Yogurt Intervention	N/A

Detailed Description

The gastrointestinal (GI) tract has the difficult task of absorbing nutrients while excluding microorganisms and non-nutritive foreign agents. The GI tract is protected by components of GI mucosal immunity, such as the mucin layer, anti-microbial peptides, secretory IgA (sIgA), and more, which collectively maintain gut homeostasis. When mucosal immunity fails, the result can be gastrointestinal infection, allergic inflammation, or inflammatory bowel disease. Mechanistic knowledge from in vitro studies suggests that sIgA increases in response to lactic acid bacteria and mucin-2 expression increases in response to milk peptides in yogurt. Yogurt consumption may also reduce constipation and increase the production of short-chain fatty acids (SCFAs). SCFAs promote the health of intestinal cells by acting as an energy source, influencing gene expression, and exerting anti-inflammatory effects. When SCFAs increase, fecal pH decreases.

This research will expand the limited existing literature on how GI mucosal immunity changes in response to yogurt consumption, the time frame over which effects occur and how long the effects persist after yogurt is discontinued. Participants will undergo a two-week baseline period without yogurt intake, followed by a three-week intervention of two daily 6-oz servings of dairy yogurt, and a follow-up period with no yogurt consumption. Stool samples will be collected at the end of the 2-week baseline period, after 1, 2, and 3 weeks of intervention, and at the end of the 2 weeks post-intervention period for measurement of fecal sIgA, fecal mucin-2 mRNA, fecal pH, and fecal SCFAs, and analysis of the fecal microbiome. 24-hour dietary recalls will be collected with the Automated Self-Administered Dietary Assessment Tool (ASA24) during the baseline and intervention phases of the trial.

Specific knowledge will be produced regarding the effect of regular yogurt consumption on sIgA levels, mucin-2 gene expression and fecal pH in older adults (age 50 - 75 years). The study will also produce knowledge on the intervention length needed for maximal response in these outcome measures and how long these responses persist when the yogurt intervention is discontinued. The outcomes of this study will 1) provide preliminary data to inform design of future, larger studies on how dairy yogurt or similar cultured products influence GI mucosal immune function, and 2) contribute to growing knowledge on the potential health benefits of consuming fermented, particularly yogurt.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Effect of Yogurt on Mucosal Immunity in the Gastrointestinal Tract

Anticipated Study Start Date :

Jul 10, 2023

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Yogurt Consumption Participants will complete a 2-week baseline with no yogurt intake, followed by a three-week yogurt intervention, and then a 2-week follow-up period with no yogurt intake.	Other: Yogurt Intervention Participants will be provided with a commercial yogurt that contains only cultured dairy, traditional live active cultures (Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, and possibly other non-brand-specific strains), sugar, and, optionally, vanilla flavor. The yogurt will contain no starches or pectin, gums, fiber or other added ingredients. Participants will be asked to consume two 6-ounce portions of yogurt each day, and to log their consumption in a provided booklet. They will be advised to incorporate the yogurt into their diet however they choose (as part of meals or as snacks), to avoid other fermented foods, and to otherwise maintain their habitual diet.

Arm

Intervention/Treatment

Experimental: Yogurt Consumption

Participants will complete a 2-week baseline with no yogurt intake, followed by a three-week yogurt intervention, and then a 2-week follow-up period with no yogurt intake.

Other: Yogurt Intervention

Participants will be provided with a commercial yogurt that contains only cultured dairy, traditional live active cultures (Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, and possibly other non-brand-specific strains), sugar, and, optionally, vanilla flavor. The yogurt will contain no starches or pectin, gums, fiber or other added ingredients. Participants will be asked to consume two 6-ounce portions of yogurt each day, and to log their consumption in a provided booklet. They will be advised to incorporate the yogurt into their diet however they choose (as part of meals or as snacks), to avoid other fermented foods, and to otherwise maintain their habitual diet.

Outcome Measures

Primary Outcome Measures

Changes in fecal secretory immunoglobulin A [After 2-week baseline; at 1, 2 and 3 weeks of intervention; and after 2-week follow-up]
Fecal secretory immunoglobulin A (sIgA) will be extracted then measured in duplicate by enzyme-linked immunosorbent assay (ELISA)

Secondary Outcome Measures

Changes in fecal mucin-2 mRNA expression [After 2-week baseline; at 1, 2 and 3 weeks of intervention; and after 2-week follow-up]
Pre-amplification and quantitative reverse transcription polymerase chair reaction (RT-qPCR) for mucin 2 (MUC2) and GAPDH will be conducted using validated TaqMan assays, and fold MUC2 gene expression of samples will be calculated relative to a commercial total human colon RNA standard using GAPDH as the housekeeping gene.
Changes in fecal pH [After 2-week baseline; at 1, 2 and 3 weeks of intervention; and after 2-week follow-up]
Fecal pH will be measured with a glass electrode pH meter.
Changes in fecal short-chain fatty acids [After 2-week baseline; at 1, 2 and 3 weeks of intervention; and after 2-week follow-up]
The most abundant fecal SCFAs, such as acetate, propionate, butyrate, will be analyzed via gas chromatography-mass spectrometry.
Fecal microbiome [After 2-week baseline; at 1, 2 and 3 weeks of intervention; and after 2-week follow-up]
Gut microbiota composition will be assessed with PCR amplification and 16S sequencing

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 50 - 75 years
BMI 18.5 - 39.9 kg/m2

Exclusion Criteria:

BMI less than 18.5 or greater than 39.9
Consumption of fermented foods or probiotics in the past two weeks
Unwillingness to abstain from non-study fermented foods and probiotics during the trial
Allergy to cow milk
Lactose intolerance
Any dietary restriction limiting or prohibiting consumption of lightly sweetened, vanilla flavored, whole milk yogurt
Uncomfortable with or unwilling to complete stool sample collections
Current participation in another research study
If female,
Currently pregnant or lactating
Have had menstrual bleeding in the past 12 months
Having fewer than 3 bowel movements per week
Unmanaged hypertension, defined as blood pressure greater than or equal to 140/90 mmHg
Current diagnosis of:
Disease that affects the immune system, including HIV/AIDS
Cancer
Diabetes
Asthma with daily medication
Primary immune deficiency
Auto-immune disease
Chronic gastrointestinal disorder (e.g. Crohn's disease, irritable bowel syndrome, colitis, gastric ulcer)
Current use for 2 weeks or longer of:
Any drug that affects the immune system, such as immunosuppressants, immune modifying drugs, or corticosteroids (e.g. cortisone, prednisone, methylprednisolone)
Biologics (e.g. Lantus, Remicade, Rituxan, Humira, Herceptin, Avastin, Lucentis, Enbrel)
Use of sulfonamides or antibiotics in the past 3 months
Use of laxatives in the past 2 weeks
Currently undergoing cancer treatment with radiation or drugs
History of gastrointestinal surgery that would impact study outcomes, such as gastric bypass, intestinal resection, surgeries of the liver or pancreas, or removal of part or all of any organ of the GI tract
Having within the past 2 weeks:
Diarrheal illness, defined as passing 3 or more abnormally loose or watery stools in a 24-hour period
Persistent vomiting
Fever
Having within the past 3 months:
Surgery
Hospitalization
Having within the past 1 month:
Colonoscopy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USDA Western Human Nutrition Research Center	Davis	California	United States	95616

Sponsors and Collaborators

USDA, Western Human Nutrition Research Center

Investigators

Principal Investigator: Danielle G Lemay, PhD, USDA, Western Human Nutrition Research Center
Principal Investigator: Bess L Caswell, PhD, USDA, Western Human Nutrition Research Center