Clinical trial NCT03952988: Effect of B.Bifidum 900791 Intake in Adult With Hypolactasia and Lactose Intolerance
Official title: Effect of the Consumption of a Probiotic (B. Bifidum 900791)-Containing Ice-cream in Adult With Hypolactasia and Lactose Intolerance
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Lactose Intolerance
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2019-05-16
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.).

Primary outcomes:
measure: Area under curve (AUC) of hydrogen in the HBT
timeFrame: Day 15
Secondary outcomes:
measure: Area under curve (AUC) of hydrogen in the HBT
timeFrame: Day 43
measure: Area under curve (AUC) of hydrogen in the HBT
timeFrame: Day 71
measure: Fecal microbiota alpha-diversity
timeFrame: Days 15
measure: Fecal microbiota alpha-diversity
timeFrame: Day 43
measure: Fecal microbiota alpha-diversity
timeFrame: Day 71
measure: Relative abundancies of the bacterial taxa forming the the fecal microbiota
timeFrame: Day 15
measure: Relative abundancies of the bacterial taxa forming the the fecal microbiota
timeFrame: Day 43
measure: Relative abundancies of the bacterial taxa forming the the fecal microbiota
timeFrame: Day 71
measure: Fecal counts of B. bifidum 900791
timeFrame: Days 15
measure: Fecal counts of B. bifidum 900791
timeFrame: Days 43
measure: Fecal counts of B. bifidum 900791
timeFrame: Days 71
measure: Fecal beta-galactosidase activity
timeFrame: Days 15
measure: Fecal beta-galactosidase activity
timeFrame: Days 43
measure: Fecal beta-galactosidase activity
timeFrame: Days 71
measure: Fecal short chain fatty acids concentrations
timeFrame: Days 15
measure: Fecal short chain fatty acids concentrations
timeFrame: Days 43
measure: Fecal short chain fatty acids concentrations
timeFrame: Days 71
measure: Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT
timeFrame: Days 15
measure: Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT
timeFrame: Days 43
measure: Scores of gastrointestinal symptoms: bloating, abdominal distention, abdominal pain, borborygms and flatulence, during the HBT
timeFrame: Days 71
Other outcomes:
Locations:
Study officials:
References:
citation: Marteau P, Pochart P, Flourie B, Pellier P, Santos L, Desjeux JF, Rambaud JC. Effect of chronic ingestion of a fermented dairy product containing Lactobacillus acidophilus and Bifidobacterium bifidum on metabolic activities of the colonic flora in humans. Am J Clin Nutr. 1990 Oct;52(4):685-8. doi: 10.1093/ajcn/52.4.685.
citation: Pelletier X, Laure-Boussuge S, Donazzolo Y. Hydrogen excretion upon ingestion of dairy products in lactose-intolerant male subjects: importance of the live flora. Eur J Clin Nutr. 2001 Jun;55(6):509-12. doi: 10.1038/sj.ejcn.1601169.
citation: Jiang T, Mustapha A, Savaiano DA. Improvement of lactose digestion in humans by ingestion of unfermented milk containing Bifidobacterium longum. J Dairy Sci. 1996 May;79(5):750-7. doi: 10.3168/jds.S0022-0302(96)76422-6.
citation: Almeida CC, Lorena SL, Pavan CR, Akasaka HM, Mesquita MA. Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients. Nutr Clin Pract. 2012 Apr;27(2):247-51. doi: 10.1177/0884533612440289. Epub 2012 Mar 8.
citation: Turroni F, Duranti S, Bottacini F, Guglielmetti S, Van Sinderen D, Ventura M. Bifidobacterium bifidum as an example of a specialized human gut commensal. Front Microbiol. 2014 Aug 21;5:437. doi: 10.3389/fmicb.2014.00437. eCollection 2014.
citation: Gargari G, Taverniti V, Balzaretti S, Ferrario C, Gardana C, Simonetti P, Guglielmetti S. Consumption of a Bifidobacterium bifidum Strain for 4 Weeks Modulates Dominant Intestinal Bacterial Taxa and Fecal Butyrate in Healthy Adults. Appl Environ Microbiol. 2016 Sep 16;82(19):5850-9. doi: 10.1128/AEM.01753-16. Print 2016 Oct 1.
citation: Hsu CA, Yu RC, Lee SL, Chou CC. Cultural condition affecting the growth and production of beta-galactosidase by Bifidobacterium longum CCRC 15708 in a jar fermenter. Int J Food Microbiol. 2007 May 1;116(1):186-9. doi: 10.1016/j.ijfoodmicro.2006.12.034. Epub 2007 Jan 19.