Clinical trial NCT02390232: Prospective Cohort Assessing the Role of the Genotoxin Colibactin From Escherichia Coli B2 in the Genesis of NASH
Official title: Prospective Cohort Assessing the Role of the Genotoxin Colibactin From Escherichia Coli B2 in the Genesis of NASH
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: gut microbiota
Non Alcoholic Steato Hepatitis
Steatohepatitis
Escherichia coli
colibactin
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-03-17
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Non Alcoholic Fatty Liver Disease

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: composition of the gut microbiota between two groups, and prevalence of the Escherichia Coli belonging to the B2 group and producing the genotoxin colibactin.
timeFrame: 1 day
Secondary outcomes:
measure: differences between the two groups
timeFrame: 1 day
measure: determine wether bacteria, in particular escherichia Coli can translocate and reach steatohepatitis patients liver
timeFrame: 1 day
measure: Exploration of a biomarker of fibrosis from blood microbiota in NAFLD patients
timeFrame: 1 day
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: CHU de Toulouse, hôpital Purpan
name: Maeva Guillaume, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.