Clinical trial NCT01399996: Influence of a Delivery System on the Efficacy of a Probiotic Intervention
Official title: Influence of a Delivery System on the Efficacy of a Probiotic Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Delayed Transit Time
Irregular Bowel Function
Keywords: probiotic
microbiota
transit time
immunity
immune function
constipation
bowel function
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: Dairy Management Inc.
First posted: 2011-07-22
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: In the proposed work we will evaluate the efficacy of a probiotic bacterium (Bifidobacterium animalis subsp. lactis BB12) delivered in a yogurt smoothie (organism to be added before or after fermentation) or as a supplement (tablet) by assessing 1) bowel habits (transit time); 2) the ecology of the bacterial community in the GIT; and 3) immune status of healthy human volunteers. In addition to providing information about the relative efficacy of the delivery vehicles on probiotic function it will provide novel information about the influence of the yogurt smoothie alone (control) on all the parameters measured.

Detailed description: Probiotics (health-promoting bacteria) are often considered "functional ingredients" that act independently of the matrix used to deliver them to the human host. This thinking ignores the impact the delivery matrix (food or dietary supplement) may have on both the physiology of the probiotic organism and on the human host and is likely not true.

Historically the most common "probiotic foods" have been fermented dairy products, particularly yogurts. Since yogurts are commonly understood to contain live "good" bacteria they are well accepted by consumers. However, increasingly over the last decade, probiotics are being added to non-dairy-based foods (juice, chocolate, cookies, etc) or consumed as supplements (tablets/capsules). While this expands the options for people to obtain probiotic organism, it is not clear whether probiotics delivered in these products are as efficacious as when delivered in a dairy food. In fact, the buffering capacity and nutrient composition of milk products may directly influence efficacy of the probiotic by increasing survival during passage through the gastrointestinal tract (GIT) and by modifying the physiology of the probiotic organism. In addition, fermentation products produced by the probiotic during manufacture of yogurt may also have an influence on the efficacy of probiotic bacteria.

Our hypotheses are:

1. The vehicle used to deliver probiotic bacteria into the body influences the performance of the probiotic in vivo. Specifically, consumption of yogurt-based smoothie containing probiotic bacteria will result in greater decrease in fecal transit time, and have a greater effect on the composition of the fecal microbiota and on markers of immune status than the same probiotic bacteria delivered at the same level in the form of a dietary supplement (tablet).
2. Timing of the addition of probiotic organism to the yogurt smoothie (pre or post fermentation) will not change the efficacy of the probiotic with respect to the outcomes being assessed.

Eligibility criteria: Inclusion Criteria:

* Generally healthy
* Men and women
* 18-40 years of age
* Body mass index between 20 and 35 kg/m\^2
* Persons with irregular bowel function as determined using the Rome III criteria (1) which is used to classify functional gastrointestinal disorders.
* Increased gastrointestinal transit time \> 60 hours.

Exclusion Criteria:

* Smoking and/or use of other tobacco products
* Blood pressure greater than 140/90 mm Hg
* A history of myocardial infarction, stroke, diabetes mellitus, liver disease, kidney disease and thyroid disease (unless controlled by medication and blood results within the previous 6 months are provided).
* Lactation, pregnancy or desire to become pregnant during the study
* Use of cholesterol-lowering medication
* Refusal to discontinue intake of putative cholesterol-lowering supplements (psyllium, fish oil capsules, soy lecithin, niacin, fiber, flax, phytoestrogens, stanol/sterol supplemented foods
* Refusal to discontinue probiotics,nutritional supplements, herbs or vitamins
* Vegetarianism/Veganism
* Lactose intolerance
* Clinical diagnosis of Inflammatory Bowel Disease (IBD), e.g. Crohn's Disease or ulcerative colitis
* Excessive alcohol consumption (\> 14 standard drinks per week)
* Chronic use of anti-inflammatory medications (unless able to discontinue)
* Individuals taking stool softeners or enemas on a regular basis.
* Allergy to polyvinyl chloride (PVC) or any other type of plastic
* Individuals with a bowel transit time of \< 60 hours at time of screening
* Individuals with swallowing disorders or dysphagia to food or pills
* Suspected strictures, fistulas, or physiological GI Obstruction
* GI surgery within the past three months
* Refusal to agree to give blood or plasma for the length of the study.

Note: If a participant experiences a delay in passing the capsule (beyond five days) they will be treated accordingly and excluded from future participation in the study.

Primary outcomes:
measure: Gastrointestinal transit time
timeFrame: Weeks 4, 10, 16, 22
Secondary outcomes:
measure: Change from baseline in the fecal microbiota profile at 4 weeks following each of the 4 interventions and 1 free living period
timeFrame: Weeks 4, 10, 16, 22 and 28
measure: Change from baseline in immune status at 4 weeks following each of the 4 interventions and 1 free living period
timeFrame: Weeks 4, 10, 16, 22, 28
Other outcomes:
Locations:
city: University Park
country: United States
facility: Penn State University
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Penny M Kris-Etherton, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drossman DA, Dumitrascu DL. Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006 Sep;15(3):237-41.
citation: Ba Z, Lee Y, Meng H, Kris-Etherton PM, Rogers CJ, Lewis ZT, Mills DA, Furumoto EJ, Rolon ML, Fleming JA, Roberts RF. Matrix Effects on the Delivery Efficacy of Bifidobacterium animalis subsp. lactis BB-12 on Fecal Microbiota, Gut Transit Time, and Short-Chain Fatty Acids in Healthy Young Adults. mSphere. 2021 Aug 25;6(4):e0008421. doi: 10.1128/mSphere.00084-21. Epub 2021 Jul 7.
citation: Lee Y, Ba Z, Roberts RF, Rogers CJ, Fleming JA, Meng H, Furumoto EJ, Kris-Etherton PM. Effects of Bifidobacterium animalis subsp. lactis BB-12(R) on the lipid/lipoprotein profile and short chain fatty acids in healthy young adults: a randomized controlled trial. Nutr J. 2017 Jun 29;16(1):39. doi: 10.1186/s12937-017-0261-6.
citation: Meng H, Lee Y, Ba Z, Peng J, Lin J, Boyer AS, Fleming JA, Furumoto EJ, Roberts RF, Kris-Etherton PM, Rogers CJ. Consumption of Bifidobacterium animalis subsp. lactis BB-12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults. Mol Nutr Food Res. 2016 May;60(5):1161-71. doi: 10.1002/mnfr.201500665. Epub 2016 Mar 1.