Effects of Nutritional Fat on the Growth of Intestinal E. Coli

NCT03800147 | Unknown

• 1 other identifier: FAT Study
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Recent experiments in the lab of Prof. WD Hardt revealed, that in mice, 24 h exposure to a high-fat diet results in a breakdown of colonization resistance against Salmonella typhimurium. Mechanistic experiments identified bile acids as the mediator for reduced colonization resistance. Exposure to a high fat diet leads to increased bile acid secretion which in turn modify the intestinal microbiota. It is now the aim to verify the results of this study in human healthy volunteers. The nutritional habits of all participants will carefully be evaluated. In the intervention phase, participants will be exposed to either high-fat or low-fat diet and a controlled dose of the non-pathogenic bacteria E. coli Nissle. E. coli Nissle is the active compound for "Mutaflor®" and other probiotics. It is planned to enumerate E. coli Nissle counts in the stool after Mutaflor ingestion and to quantify other changes of the human microbiota. The hypothesis is that a high-fat diet leads to increased bile acid secretion results in favorable growth conditions for E. coli Nissle, resulting in high bacterial counts in the stool.

Conditions

Escherichia Coli Infections

Outcome Measures

Primary Outcomes (2)

• Maximum concentration of E. coli Nissle bacteriae in all stool samples of each participant

  Each participant's fecal samples will be analyzed for E. coli Nissle bacteriae. Only the stool samples acquired in intervention phase 1 will be considered. For each participant, the maximum concentration of E. coli Nissle in all stool samples (assessed by qPCR) will be used for the calculation of the primary outcome.

  1, 2 and 5 days after E. coli Nissle inoculation

• Comparison of E. coli Nissle concentration in feces between high-fat diet and low-fat diet

  The concentration of E. coli Nissle bacteriae (CFU per g feces) in participants exposed to high-fat diet will be compared to the concentration of E. coli Nissle bacteriae in individuals exposed to low-fat diet (Mann-Whitney U test, a p-value \<0.05 will be considered significant).

  1, 2 and 5 days after E. coli Nissle inoculation

Secondary Outcomes (6)

• Chemical composition of blood

  Week 1 - 8

• Chemical composition of stool

  Week 1 - 8

• Microbiota composition: taxonomic composition

  Week 1 - 8

• Microbiota composition: metagenomic properties

  Week 1 - 8

• Microbiota composition: E. coli content

  Week 1 - 8

Study Arms (2)

High-fat diet

ACTIVE COMPARATOR

Participants will follow a high-fat diet. During the intervention phase, they will inoculate "Mutaflor Suspension" (E. coli Nissle 1917) (Single dose, 5 ml = 5x10\^8 CFU). Blood samples, stool samples and clinical information will be collected during the study.

Drug: "Mutaflor Suspension" (E. coli Nissle 1917); Other: Blood samples; Other: Stool samples; Other: Clinical information

Low-fat diet

ACTIVE COMPARATOR

Participants will follow a low-fat diet. During the intervention phase, they will inoculate "Mutaflor Suspension" (E. coli Nissle 1917) (Single dose, 5 ml = 5x10\^8 CFU). Blood samples, stool samples and clinical information will be collected during the study.

Drug: "Mutaflor Suspension" (E. coli Nissle 1917); Other: Blood samples; Other: Stool samples; Other: Clinical information

Interventions

"Mutaflor Suspension" (E. coli Nissle 1917) DRUG

Inoculation of "Mutaflor Suspension" (E. coli Nissle 1917)

Also known as: Mutaflor Suspension

High-fat diet; Low-fat diet

Blood samples OTHER

Blood samples will be collected and analyzed at different study time points

High-fat diet; Low-fat diet

Stool samples OTHER

Stool samples will be collected and analyzed at different study time points

High-fat diet; Low-fat diet

Clinical information OTHER

Clinical information will be collected at different study time points using questionnaires

High-fat diet; Low-fat diet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals free of abdominal complaints or symptoms
• Written informed consent
• Age 18 - 85 years
• Working at ETH Zurich or University of Zurich and trained and experienced in handling -80°C freezers at biosafety level 2.

You may not qualify if:

• Previous history of gastrointestinal disease or surgery (excludes appendectomy, hernia repair and surgery for anorectal disorders)
• Known diabetes mellitus, scleroderma, neurological impairment or other major diseases requiring ongoing management
• Immunesuppression
• Subjects with antibiotic therapy, proton pump inhibitors or laxatives within the last four weeks
• Pregnancy beyond week 12. "Mutaflor" intake is safe during pregnancy; however, special regulations are required to gain access to the -80°C freezers. No pregnancy test will be performed.

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Institute of Microbiology (D-BIOL), ETH Zurich

Zurich, 8093, Switzerland

Location

MeSH Terms

Conditions

Escherichia coli Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Wolf-Dietrich Hardt, Prof. Dr.

  ETH Zurich, Institute of Microbiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Misselwitz, MD

CONTACT

+41 44 255 1111; benjamin.misselwitz@usz.ch

Wolf-Dietrich Hardt, Prof. Dr.

CONTACT

+41 44 632 51 43; hardt@micro.biol.ethz.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Participants will not be blinded regarding the composition of their nutrition. Investigators performing stool and blood analyses will be blinded to the group assignment of the participants.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized controlled crossover clinical study

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: January 11, 2019
• Study Start: January 24, 2019
• Primary Completion: September 24, 2019
• Study Completion: September 24, 2019
• Last Updated: January 11, 2019

Record last verified: 2019-01

Locations

CH (1)