Effect of B.Bifidum 900791 Intake in Adult With Hypolactasia and Lactose Intolerance

Study Overview
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Brief Summary
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Lactase is high in the newborn intestine, allowing him to digest the high amounts of lactose present in breastmilk. From weaning, lactase is genetically programmed to decrease, reaching residual levels in the adult. This situation occurs in 75% of the world population and is known as adult primary hypolactasia while the remaining 25% is lactase persistent i.e. maintains in adulthood lactase values similar to these of newborns. In subjects with hypolactasia, the intake of milk products can produce digestive symptoms, making that the affected individuals spontaneously reduce the consumption of these products and, therefore, their intake of calcium and proteins. In addition to lactose-free milk and exogenous lactase, a strategy for the intolerant subjects to continue consuming dairy products is, for example, to consume yogurt, due to the fact that the lactase of the yogurt bacteria continues to function in the intestine of the consumer, hydrolyzing lactose and decreasing the development of digestive symptoms. Similarly, many probiotic strains, such as L. acidophilus NCFM, L. casei CRL431, B. longum 401 and B. bifidum Orla Jensen 1424, express β-galactosidases that hydrolyze lactose, preventing its fermentation and the production of gases. The acute administration of these strains improves lactose tolerance. In addition, a recent study reported that dietary supplementation of intolerant subjects for 4 weeks with L. casei Shirota and B. breve Yakult reduced digestive symptoms and breath hydrogen excretion not only at the end of the period of administration of the probiotics but also 3 months after having discontinued the use of probiotics. Based on this background, the aim of this study is to determine whether the regular consumption of an ice cream with the strain B. bifidum 900791 improves lactose intolerance in hypolactasic subjects, even after the suspension of the consumption of the product. To determine if this effect is due to the adaptation of the microbiota, the investigators will also evaluate changes in the composition of the microbiota and the generation of volatile fatty acids.

Official Title
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Effect of the Consumption of a Probiotic (B. Bifidum 900791)-Containing Ice-cream in Adult With Hypolactasia and Lactose Intolerance

Conditions
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Lactose Intolerance

Intervention / Treatment
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* Dietary Supplement: Probiotic ice cream
* Dietary Supplement: Placebo ice cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of hypolactasia and lactose intolerance Exclusion Criteria: Diarrhea Previous gastrointestinal pathologies Current or recent intake of antibiotics, anti-inflammatory drugs, laxatives or drugs interfering with intestinal transit Alterations of intestinal anatomy or function Pregnancy Chronic diseases of different etiologies (auto-immune, inflammatory, tumor, etc.).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At Day 1, hypolactasic subjects will perform a Hydrogen Breath Test (HBT) with a placebo ice-cream with 20g lactose (Negative Control). A second HBT will be carried at Day-8 with the same product + an exogenous lactase (Positive control). A 3° HBT will be carried out at Day 15 with the probiotic ice cream with 20g lactose to determine the acute effect of the probiotic. Posteriorly, the subjects will be randomly assigned in one of 2 groups to consume an ice-cream/d, with or without the probiotic, for 4 weeks. At Day-43, they will carry out a 4° HBT with ice cream with 20g lactose and without probiotic (Evaluation of the chronic effect). At Day 71, after 4 weeks washout period, a 5° HBT will be carried out with the ice cream with lactose and without probiotic, to evaluate the remanence of the effect. A fresh stool will be obtained at days 15, 43 and 71 to determine the presence of the probiotic, microbiota composition, ß-galactosidase activity and short chain fatty acid concentrations.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br> | Dietary Supplement: Probiotic ice cream<br>* One portion (50g) of an ice-cream containing the probiotic B. bifidum 900791 (>10(exp7)/g) every day for 4 weeks<br>* Other names: Bifidice;|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo ice cream<br>* One portion (50g) of an ice-cream without probiotic every day for 4 weeks<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve (AUC) of hydrogen in the HBT | Acute effect of the probiotic on hydrogen excretion after lactose ingestion | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve (AUC) of hydrogen in the HBT | Chronic effect of the probiotic on hydrogen excretion after lactose ingestion | Day 43 | 
| Area under curve (AUC) of hydrogen in the HBT | Remanent effect of the probiotic on hydrogen excretion after lactose ingestion after one month without probiotic ingestion | Day 71 | 
| Fecal microbiota alpha-diversity | Shannon Index | Days 15 | 
| Fecal microbiota alpha-diversity | Shannon Index | Day 43 | 
| Fecal microbiota alpha-diversity | Shannon Index | Day 71 | 
| Relative abundancies of the bacterial taxa forming the the fecal microbiota | Relative abundancies of the different bacterial taxa detected by high throughput sequencing | Day 15 | 
| Relative abundancies of the bacterial taxa forming the the fecal microbiota | Relative abundancies of the different bacterial taxa detected by high throughput sequencing | Day 43 | 
| Relative abundancies of the bacterial taxa forming the the fecal microbiota | Relative abundancies of the different bacterial taxa detected by high throughput sequencing | Day 71 | 
| Fecal counts of B. bifidum 900791 | B. bifidum 900791 counts in fecal samples | Days 15 | 
| Fecal counts of B. bifidum 900791 | B. bifidum 900791 counts in fecal samples | Days 43 | 
| Fecal counts of B. bifidum 900791 | B. bifidum 900791 counts in fecal samples | Days 71 | 
| Fecal beta-galactosidase activity | Determination of the microbial beta-galactosidase activity in fecal samples (expressed as U/g) | Days 15 | 
| Fecal beta-galactosidase activity | Determination of the microbial beta-galactosidase activity in fecal samples (expressed as U/g) | Days 43 | 
| Fecal beta-galactosidase activity | Determination of the microbial beta-galactosidase activity in fecal samples (expressed as U/g) | Days 71 | 
| Fecal short chain fatty acids concentrations | Determination of short chain fatty acids concentrations in fecal samples | Days 15 | 
| Fecal short chain fatty acids concentrations | Determination of short chain fatty acids concentrations in fecal samples | Days 43 | 
| Fecal short chain fatty acids concentrations | Determination of short chain fatty acids concentrations in fecal samples | Days 71 | 
| Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT | Determination of gastrointestinal symptoms (bloating, abdominal distention, abdominal pain, borborygms and flatulence) using a previously validated questionnaire on a scale of 0 (none), 1 (mild), 2 (moderate), 3 (severe). We will define clinically relevant ymptoms as a composite score of 3 or more during the HBT. | Days 15 | 
| Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT | Determination of gastrointestinal symptoms (bloating, abdominal distention, abdominal pain, borborygms and flatulence) using a previously validated questionnaire on a scale of 0 (none), 1 (mild), 2 (moderate), 3 (severe). We will define clinically relevant ymptoms as a composite score of 3 or more during the HBT. | Days 43 | 
| Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT | Determination of gastrointestinal symptoms (bloating, abdominal distention, abdominal pain, borborygms and flatulence) using a previously validated questionnaire on a scale of 0 (none), 1 (mild), 2 (moderate), 3 (severe). We will define clinically relevant ymptoms as a composite score of 3 or more during the HBT. | Days 71 |