Prospective Cohort Assessing the Role of the Genotoxin Colibactin From Escherichia Coli B2 in the Genesis of NASH (Coli-NASH)

In a population of patients with Non Alcoholic Fatty Liver Disease (NAFLD), the investigators will compare the composition of the gut microbiota from patients with simple steatosis with that with steatohepatitis.

The purpose of this study is to determine if the pathogenic Escherichia Coli to the B2 group and producing the genotoxin colibactin is a factor for developing NASH.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Biological: liver biopsy; Biological: collection of stools; Biological: blood sample

Detailed Description

Gut microbiota composition is now linked to the onset of obesity, metabolic disorders, and Non Alcoholic Fatty Liver Disease . While simple steatosis has benign prognosis, steatohepatitis (NASH) leads to cirrhosis and hepatocarcinoma and increases cardiovascular and cancer- related mortality. Some Escherichia coli (E. coli) belonging to the B2 phylogenetic group are involved in many diseases. Those producing the genotoxin colibactin are in addition known to induce a chronic alteration of intestinal permeability, one of the major factors leading to NASH.

• Study Type: Observational
• Enrollment (Actual): 176

Contacts and Locations

Study Locations

• France
  • Toulouse, France
    • CHU Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Non Alcoholic Fatty Liver Disease

Description

Inclusion Criteria:

• NAFLD
• indication of liver biopsy

Exclusion Criteria:

• presence of any other cause of liver or steatosis
• alcohol consumption exceeding 30 g / day for a men and 20 g / day for a woman
• a history of decompensated cirrhosis
• treatment with prebiotics, probiotics or antibiotics in the month prior to inclusion
• chronic gastrointestinal disease or history of gastrointestinal surgery
• pregnancy or breastfeeding
• patient under guardianship

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NAFLD with simple steatosis; Patients with NAFLD with simple steatosis: collection of stools, blood sample and liver biopsy	Biological: liver biopsy; A small needle is inserted into the liver to collect a tissue sample; Biological: collection of stools; collection of stools; Biological: blood sample; collection of blood sample
NAFLD with steatohepatitis; Patients with NAFLD with steatohepatitis: collection of stools, blood and liver biopsy	Biological: liver biopsy; A small needle is inserted into the liver to collect a tissue sample; Biological: collection of stools; collection of stools; Biological: blood sample; collection of blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composition of the gut microbiota between two groups, and prevalence of the Escherichia Coli belonging to the B2 group and producing the genotoxin colibactin.	compare the composition of the gut microbiota between patients with simple steatosis with steatohepatitis, and determinate the prevalence of the Escherichia Coli belonging to the B2 group and producing the genotoxin colibactin.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
differences between the two groups	highlight other differences between the two cohort	1 day
determine wether bacteria, in particular escherichia Coli can translocate and reach steatohepatitis patients liver	determine if bacteria, in particular escherichia Coli can translocate and reach steatohepatitis patients liver	1 day
Exploration of a biomarker of fibrosis from blood microbiota in NAFLD patients	Determination of bacterial translocation assay PCR 16S bacterial gene in blood and sequence and analyse the microbiota.	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Maeva Guillaume, Doctor, CHU de Toulouse, Hôpital Purpan

Publications and helpful links

General Publications

• Smati S, Polizzi A, Fougerat A, Ellero-Simatos S, Blum Y, Lippi Y, Regnier M, Laroyenne A, Huillet M, Arif M, Zhang C, Lasserre F, Marrot A, Al Saati T, Wan J, Sommer C, Naylies C, Batut A, Lukowicz C, Fougeray T, Tramunt B, Dubot P, Smith L, Bertrand-Michel J, Hennuyer N, Pradere JP, Staels B, Burcelin R, Lenfant F, Arnal JF, Levade T, Gamet-Payrastre L, Lagarrigue S, Loiseau N, Lotersztajn S, Postic C, Wahli W, Bureau C, Guillaume M, Mardinoglu A, Montagner A, Gourdy P, Guillou H. Integrative study of diet-induced mouse models of NAFLD identifies PPARalpha as a sexually dimorphic drug target. Gut. 2022 Apr;71(4):807-821. doi: 10.1136/gutjnl-2020-323323. Epub 2021 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: February 25, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimate): March 17, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: gut microbiota; Steatohepatitis; Escherichia coli; Non Alcoholic Steato Hepatitis; colibactin
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Escherichia coli Infections
• Other Study ID Numbers: RC31/14/7319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO