Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Dysbiosis (EBP)

Evidence Based Probiotic Therapy of Proton Pump Inhibitor Induced Gastrointestinal Discomfort and Oralization of the Gut Microbiome: An Open-label Pilot Single-arm Trial

In this study the investigators aim to test whether an evidence based probiotic is able to revert proton pump inhibitor induced dysbiosis of the gut microbiome.

Study Overview

• Status: Recruiting
• Conditions: Dysbiosis
• Intervention / Treatment: Dietary supplement: Intervention

Detailed Description

With the emergence of high throughput sequencing techniques, researchers obtained the necessary tools to launch in-depth investigations into the structure and function of the intestinal microbiome. For the first time, it was possible to describe the influence of genetics, environment, nutrition and diseases on the microbiome and identify major determinants. One of the most prominent influencing factors on the composition of the microbiome is the use of proton pump inhibitors (PPI), in the general population as well as in chronic diseases, such as liver cirrhosis.

Proton pump inhibitors are used to treat gastric acid related diseases. They drastically reduce the secretion of gastric acid and thereby increase the gastric pH. The reduction of gastric acid production, however, allows acid-sensitive food-borne and oral bacteria to pass the stomach unharmed and colonize the more distal parts of the intestine. In addition, PPI use creates less favorable conditions for typical gut commensals and reduces the microbial diversity in the intestine. These alterations in the microbiome can be linked to PPI side effects, such as gastrointestinal symptoms (e.g., abdominal discomfort, bloating, constipation or diarrhea) and an increased risk for enteral infections. In patients with liver cirrhosis, PPI-induced changes in the microbiome, namely Streptococcus salivarius and Veillonella parvula - two oral bacteria, are linked to intestinal inflammation and gut permeability and predict a higher risk of complications and a higher three-year liver related mortality. These are considerable risks that need to be weighed against the benefits of the therapy. Reduction of PPI use to cases with a clear indication is one important measure to reduce potential harm of the treatment. However, many patients require long-term treatment, e.g. for gastroesophageal reflux disease or to prevent gastrointestinal bleeding when drugs with a high risk of bleeding are used (such as thrombocyte aggregation inhibitors and oral anticoagulation). Therefore, strategies to reduce oralization and thereby symptoms and negative consequences of PPI are necessary.

One possibility to change the composition of the gut microbiome is the use of probiotic bacteria. Probiotics are live microorganisms that have been demonstrated to alter the gut microbiome and exhibit positive effects on numerous gastrointestinal complaints, strengthen the gut barrier and reduce inflammation parameters. The investigators previously showed in a pilot study that a multispecies probiotic was able to improve gut permeability biomarkers in patients with long-term PPI therapy as well as gastrointestinal symptoms. However, this product was not able to efficiently reverse oralization. Therefore, the investigators conducted a series of experiments, including direct and indirect pathogen inhibition tests to identify probiotic strains that are capable of inhibiting the growth of Streptococcus salivarius and Veillonella parvula in vitro to design an evidence based probiotic mixture. The investigators screened 43 QPS (Qualified presumption of safety, granted by the European Food Safety Authority) certified probiotic strains and identified 5 strains as potential therapeutic agents to prevent/treat PPI induced oralization (unpublished data).

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vanessa Stadlbauer, Association Prof Dr; Phone Number: 385 0043 316; Email: vanessa.stadlbauer@medunigraz.at

Study Locations

• Austria
  • Graz, Austria
    • Recruiting
    • Medical University Graz
    • Contact: Vanessa Stadlbauer-Köllner, MD; Phone Number: 82282 0043 316 385; Email: vanessa.stadlbauer@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18;
• Signed Informed Consent;
• PPI intake for at least 3 months;
• Willing to accept use of all encoded data, including publication, and the confidential use and storage of all data for at least 15 years; Exclusion criteria
• Diagnosed with a gastrointestinal infection within 4 weeks prior to screening; Severe gastrointestinal disorders (e.g. inflammatory bowel diseases)
• Received any of the following products/medication prior to screening: systemic antibiotics, prokinetics, prebiotic supplements, probiotic supplements within 4 weeks prior to screening;
• Concomitant diseases or other circumstances that suggest that the patients are not eligible for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; The study product contains Lactobacillus acidophilus W53, Lactobacillus acidophilus W55, Lactobacillus casei W56, Lactobacillus plantarum W1, Lactobacillus plantarum W21, Lactobacillus rhamnosus W71, and Pediococcus acidilactici W143.	Dietary supplement: Intervention; multispecies probiotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in overall symptom score	Gastrointestinal quality of life index (GIQLI)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other dimension of gastrointestinal quality of life	Gastrointestinal quality of life index (GIQLI)	3 months
Composition of the faecal metabolome	NMR metabolomics	3 months
Zonulin	measurement of faecal zonulin	3 months
Calprotectin	measurement of faecal calprotectin	3 months
Diaminooxidase	measurement of serum diaminooxidase	3 months
lipopolysaccharide binding protein	measurement of serumlipopolysaccharide binding protein	3 months
soluble CD14	measurement of serum soluble CD14	3 months
Veillonella parvula	measurement of stool Veillonella parvula gene abundance	3 months
Streptococcus salivarius	measurement of stool Streptococcus salivarius gene abundance	3 months

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: CBmed Ges.m.b.H.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Dysbiosis
• Other Study ID Numbers: 35-175 ex 22/23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Microbiome data will be shared in a public repository, other data will depend on results and IPR discussions between partners
• IPD Sharing Time Frame: Microbiome data will be shared in a public repository when the paper will be submitted, other data will depend on results and IPR discussions between partners
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No