Safety and Viability of an E. Coli Nissle Colibactin Knockout in Healthy Volunteers

Max Nieuwdorp20 enrolled

Overview

E. coli Nissle (EcN) is a well-established human probiotic. However, it has been found that it produces colibactin, linked to colorectal cancer. In this safety trial, the safety and properties of a novel, colibactin-knockout EcN strain (EcNΔClbP) is investigated.

In this randomised controlled intervention study, the investigators will compare EcN vs. EcN colibactin-knockout (EcNΔClbP), given once daily for 7 days, in a population of healthy individuals. Safety will be established using adverse event reporting, study visits and laboratory parameters. Pharmacokinetics will be established at the beginning and the end of the study. EcN/EcNΔClbP gut engraftment properties and effects on gut microbiome composition will be assessed using fecal analyses (qPCR, shotgun metagonmics). In addition, effects on glucose homeostasis will be studied using continuous glucose monitoring.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Diabetes

Interventions

EcN Colibactin knockoutDIETARY_SUPPLEMENT

E coli Nissle strain with ClbP-gene removed and therefore not producing colibactin

E Coli NissleDIETARY_SUPPLEMENT

E Coli wildtype strain

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria: * Healthy male or female of Caucasian descent * If female, postmenopausal * Age: 18-65 years old * BMI: 18-25 kg/m2 * Subjects should be able to give informed consent Exclusion Criteria: * Use of any systemic medication (except for paracetamol), including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period. * Use of the EcN probiotic strain (Mutaflor®) in the past 12 months. * (Expected) prolonged comprised immunity (e.g. due to recent cytotoxic chemotherapy or human immunodeficiency viruses (HIV) infection with a CD4-T cell count \< 240/mm3). * History of moderate to severe disease of the digestive tract, such as celiac disease, chronic diarrhoea (≥3 stools/day for \>4 weeks), chronic obstipation (\<2 defecations/week for \>3 months), Irritable Bowel Syndrome (IBS) (according to Rome IV criteria) or Inflammatory Bowel Disease (IBD). * Any gastro-intestinal disorder within the past 6 months * Smoking or illicit drug use (e.g. amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period. * Use of \>21 units of alcohol per week on average in the past three months or use of \>2 units of alcohol during the study period. * Simultaneous participation in other studies

Locations (1)

Amsterdam UMC location AMC

Amsterdam, Netherlands

Outcomes

Primary Outcomes

Adverse events

The number, duration and severity of adverse reactions to assess the safety/tolerability of the EcNΔClbP strain compared to the wild type strain.

Time frame: 3 weeks

CRP

Changes in CRP (mg/L)