A Novel Formulation of Bifidobacterium Longum BB536 and Lactobacillus Rhamnosus HN001 With Vitamin B6 on IBS Patients

Irritable Bowel Syndrome Clinical Trial

— LLB  

Official title:

The Beneficial Effects of a Novel Formulation of Bifidobacterium Longum BB536 and Lactobacillus Rhamnosus HN001 With Vitamin B6 on Gut Microbiota and Intestinal Permeability in IBS Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03815617
• Other study ID #: 4651
• Status: Completed
• Phase: Phase 3
• Start date: February 1, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: January 2019
• Source: University of Bari
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal disorder with a prevalence ranging from 10 to 15 percent. IBS results from an interaction among several factors, including genetic predisposition, gastrointestinal motility, visceral hypersensitivity, immune activation with minimal inflammation, alterations in intestinal microbiota, increased intestinal permeability, and food sensitivity. Of note, the management of patients with IBS is critical. Since quantitative and qualitative disturbances of intestinal microbiota can occur in IBS, interesting data support the use of probiotics to modulate intestinal microbiota. The present study aimed to investigate the effects of a novel formulation of B. longum BB536 and L. rhamnosus HN001 with vitamin B6 on the gut microbiota and intestinal permeability in IBS subjects.

Description:

Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal disorder with a prevalence ranging from 10 to 15 percent. It is characterized by recurrent chronic abdominal pain or discomfort in the absence of detectable organic causes with two or more of the following conditions: onset associated with a change in frequency of stool, onset associated with a change in form (appearance) of stool, or improvement with defecation.

IBS results from an interaction among several factors, including genetic predisposition, gastrointestinal motility, visceral hypersensitivity, immune activation with minimal inflammation, alterations in intestinal microbiota, increased intestinal permeability, and food sensitivity.

IBS is associated with a high economic burden for the health care costs and work absenteeism.

The disease course is represented by unchanged symptoms in 30 to 50 percent or progression of symptoms in 2 to 18 percent. On the other hand, an improvement in symptoms was recorded in 12 to 38 percent of patients.

Of note, the management of patients with IBS is critical. Several therapeutic options have been proposed looking to the underlying pathophysiological mechanisms (i.e., dietary modification, osmotic laxatives, lubiprostone, guanylate cyclase agonists, 5-hydroxytryptamine (serotonin) 4 receptor agonists, antidiarrheal agents, bile acid sequestrants, 5-hydroxytryptamine (serotonin) 3 receptor antagonists, antispasmodic agents, antidepressants, antibiotics, probiotics, behavior modification, anxiolytics, mast cell stabilizer, and fecal transplantation).

Since quantitative and qualitative disturbances of intestinal microbiota can occur in IBS, interesting data support the use of probiotics to modulate intestinal microbiota. The genus Bifidobacterium is one of the most representative member of the intestinal microbiota with large effects on overall gut physiology. Its metabolic activity results from the degradation of oligo-fructose, production of acetate, and promotion of butyrate production by means of cross-feeding. In particular, B. longum has beneficial effects on the immune system, and can be considered a promising candidate for prevention/treatment of immune-mediated inflammatory diseases.

The combination of specific bacterial strains of Lactobacillus with Bifidobacterium species plays an interesting role in reserving the intestinal dysbiosis. The synergic action results in survival on adverse gastrointestinal conditions, adhesion to intestinal mucosa, immunomodulatory activities, and restoration of gut environment.

The present study aimed to investigate the effects of a novel formulation of B. longum BB536 and L. rhamnosus HN001 with vitamin B6 on the gut microbiota and intestinal permeability in IBS subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 31, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Diagnosis of IBS according to Rome IV Criteria

Exclusion Criteria:

• Diagnosis of structural abnormality of the GI tract

• Inflammatory bowel disorders

• Biliary duct obstructions

• Gallstones

• Abdominal surgery within the previous six months

• Infective diseases

• Drug or alcohol abuse

• Metabolic disturbances

• Mental illness

• Concomitant immunological, haematological or neoplastic disease

• Severe hepatic insufficiency (i.e., Child-Pugh class C)

• Severe heart failure (NYHA class III-IV)

Related Conditions & MeSH terms

• Irritable Bowel Syndrome

Intervention

Dietary Supplement:
• Zircombi
Twenty-five IBS patients (Rome IV criteria) (M:F= 8:17; age 48 yrs ± 11 SD) were enrolled and randomized to treatment or placebo in a a crossover randomized double-blind two-block placebo-controlled trial. Abdominal pain and bloating, intestinal habits, severity of disease, intestinal permeability, and intestinal microbiota were performed at the different time points.
• Placebo
Given as comparable packets. Same duration.

Locations

Country	Name	City	State
Italy	Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School	Bari	BA

Sponsors (1)

Lead Sponsor	Collaborator
University of Bari

Country where clinical trial is conducted

Italy, 

References & Publications (13)

2. Mearin F, Lacy BE, Chang L, et al. Bowel Disorders. Gastroenterology. 2016. doi:10.1053/j.gastro.2016.02.031

Bonfrate L, Tack J, Grattagliano I, Cuomo R, Portincasa P. Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options. Scand J Gastroenterol. 2013 Sep;48(9):995-1009. doi: 10.3109/00365521.2013.799220. Review. — View Citation

Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012 Oct 25;367(17):1626-35. doi: 10.1056/NEJMra1207068. Review. — View Citation

El-Serag HB, Pilgrim P, Schoenfeld P. Systemic review: Natural history of irritable bowel syndrome. Aliment Pharmacol Ther. 2004 Apr 15;19(8):861-70. Review. — View Citation

Falony G, Vlachou A, Verbrugghe K, De Vuyst L. Cross-feeding between Bifidobacterium longum BB536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose. Appl Environ Microbiol. 2006 Dec;72(12):7835-41. Epub 2006 Oct 20. — View Citation

Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Epub 2014 Jun 10. — View Citation

Khailova L, Petrie B, Baird CH, Dominguez Rieg JA, Wischmeyer PE. Lactobacillus rhamnosus GG and Bifidobacterium longum attenuate lung injury and inflammatory response in experimental sepsis. PLoS One. 2014 May 15;9(5):e97861. doi: 10.1371/journal.pone.0097861. eCollection 2014. — View Citation

Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4. doi: 10.1016/j.cgh.2012.02.029. Epub 2012 Mar 15. — View Citation

Markowiak P, Slizewska K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients. 2017 Sep 15;9(9). pii: E1021. doi: 10.3390/nu9091021. Review. — View Citation

Milani C, Lugli GA, Duranti S, Turroni F, Mancabelli L, Ferrario C, Mangifesta M, Hevia A, Viappiani A, Scholz M, Arioli S, Sanchez B, Lane J, Ward DV, Hickey R, Mora D, Segata N, Margolles A, van Sinderen D, Ventura M. Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut. Sci Rep. 2015 Oct 28;5:15782. doi: 10.1038/srep15782. — View Citation

Rios-Covian D, Gueimonde M, Duncan SH, Flint HJ, de los Reyes-Gavilan CG. Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett. 2015 Nov;362(21). pii: fnv176. doi: 10.1093/femsle/fnv176. Epub 2015 Sep 28. — View Citation

Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R. The burden of selected digestive diseases in the United States. Gastroenterology. 2002 May;122(5):1500-11. — View Citation

Toscano M, De Grandi R, Stronati L, De Vecchi E, Drago L. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study. World J Gastroenterol. 2017 Apr 21;23(15):2696-2704. doi: 10.3748/wjg.v23.i15.2696. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analogue Scale, ranging from 0 to 100	For assessing abdominal pain and bloating	Baseline
Primary	Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS)	Developed by Francis et al. (1997), and categorized as follows: remission (score <75), mild (75-175), moderate (175-300) and severe (>300).	Baseline
Primary	Bristol Stool Form Scale (BSFS)	To assess bowel movements, consisting of a self-report instrument for classifying stool form into seven types ranging from "separate hard lumps like nuts" (type 1) to "watery, no solid pieces" (type 7)	Baseline
Primary	MEDSTYLE questionnaire	A custom-designed questionnaire, tested across different ages, and anthropometric groups in health and disease, to measure anthropometric data, medical history, lifestyle and daily intake of foods. Frequency (day, week or month) and portion sizes (small, medium and large, represented by color pictures) of food consumption were estimated by using 35 food items (156 foods).The adherence to a Mediterranean diet was calculated by analyzing nine food categories with a score ranging from 0 point (lowest adherence) to 18 points (highest adherence).	Baseline
Primary	Intestinal permeability	It was assessed by oral administration of four sugar probes, which selectively characterize the permeability from different tracts of the gastrointestinal system. Sucrose (SO) was used as a marker of gastro-duodenal permeability; lactulose (LA) and mannitol (MA) were used as markers of small intestine permeability also as (LA/MA), and sucralose (SU) as marker of; 8 colonic permeability.	Baseline
Primary	Cultivable intestinal microbiota	It was evaluated by faecal samples (5 g) were mixed with 45 mL sterilized physiological solution and homogenized.	Baseline
Primary	Community level catabolic profiles	Biolog Eco microplates (Biolog, Inc., Hayward, CA, USA) were used to estimate the microbial diversity.	Baseline
Primary	Fecal metabolome	Three grams of fecal sample were placed into 10 mL glass vials and added with 10 µL of 4-methyl- 2-pentanol (final concentration of 33 mg/L) as the internal standard.	Baseline