Gut Microbiota and Modulation of Liver Damage in NAFLD

NCT02158351 | Completed

• 1 other identifier: 2943/14.11.2013
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Several experimental data suggest that gut-derived endotoxin and GM composition can act as a "second hit" or insult to convert hepatic SS to NASH and cause both local hepatic and systemic inflammation.This study's aim is to analyze microbiota diversity, providing information both on intestinal microbial composition and on the metabolic processes linked to them. In addition, we will correlate, for the first time, GM composition to hepatic and white adipose tissue gene expression patterns of interest and serum and fecal markers possibly related to impaired fat storage and inflammation. We aim to provide preliminary data to design future intervention studies with pre- or probiotics or bile acid derivatives to prevent/treat inflammation and fibrosis in NAFLD patients.

Conditions

Simple Steatosis (SS); Non-alcoholic Steatohepatitis (NASH); Obesity

Keywords

Simple steatosis (SS); Non-alcoholic steatohepatitis (NASH); Gut microbiota (GM); Non alcoholic fatty liver disease (NAFLD)

Outcome Measures

Primary Outcomes (1)

• gut microbiota composition

  In patients with simple steatosis SS vs those with NASH the gut microbiota composition is different even after BMI normalization

  12 months

Secondary Outcomes (2)

• In each patient group overall gut microbiota composition, and hepatic and (only in the obese patients submitted to bariatric surgery) adipose tissue mRNA expression of relevant lipid and inflammatory response pathways

  12 months

• In each patient group overall gut microbiota composition, and hepatic and (only in the obese patients submitted to bariatric surgery) adipose tissue mRNA expression of relevant lipid and inflammatory response pathways

  12 months

Other Outcomes (1)

• In each group, overall gut microbiota composition, and serum fasting and (only in the obese patients) post-prandial bile acid levels, serum markers of inflammation and liver damage and white adipose tissue mRNA expression of relevant genes

  18 months

Study Arms (2)

Simple steatosis

We will run a cross-sectional observational study including two groups of human subjects: patients with simple steatosis (SS) or non-alcoholic steatohepatitis (NASH). Grouping in patients SS or NASH will be performed based on the histological diagnosis of the type of NAFLD obtained at operation (sleeve gastrectomy or cholecystectomy). BMI will be considered as a confounding variable to be statistically analyzed. Main hypothesis: GM can lead to liver inflammation in patients with liver fat accumulation.

Procedure: liver and white adipose tissue biopsies

Non-alcoholic steato-hepatitis

We will run a cross-sectional observational study including two groups of human subjects: patients with simple steatosis (SS) or non-alcoholic steatohepatitis (NASH). Grouping in patients SS or NASH will be performed based on the histological diagnosis of the type of NAFLD obtained at operation (sleeve gastrectomy or cholecystectomy). BMI will be considered as a confounding variable to be statistically analyzed. Main hypothesis: GM can lead to liver inflammation in patients with liver fat accumulation.

Procedure: liver and white adipose tissue biopsies

Interventions

liver and white adipose tissue biopsies PROCEDURE

Non-alcoholic steato-hepatitis; Simple steatosis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

two groups of patients with morbid obesity undergoing sleeve gastrectomy will be enrolled. Grouping in patients with simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) will be performed based on the histological diagnosis of the type of NAFLD obtained at operation. Two groups of non-obese patients undergoing cholecystectomy for gallstone disease will be enrolled. Grouping in patients with simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) will be performed based on the histological diagnosis of the type of NAFLD obtained at operation.

You may qualify if:

• Male or female, equal or over 18 years old
• Eligible for Sleeve Gastrectomy for obesity with BMI 35-50 kg/m2
• Eligible for Cholecystectomy for symptomatic gallstones and bright liver at ultrasounds
• Alcohol consumption is less than 20 g/d

You may not qualify if:

• Having liver disease of other etiology
• Having advanced liver disease
• Having abnormal coagulation or other reason contraindicating a Liver Biopsy
• On regular intake of medications known to cause or exacerbate steatohepatitis or antibiotic, pre- or probiotics in the previous 3 months
• Use of vitamin E or fish oil supplements in the previous 2 months
• Alcohol consumption of more than 20 g/dl
• Inflammatory bowel diseases
• previous gastrointestinal surgery modifying the anatomy (prior to bariatric surgery)
• Pregnancy or lactating state

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Göteborg University: collaborator

Study Sites (1)

Stefano Ginanni Corradini

Rome, 00161, Italy

Location

Related Publications (32)

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Biospecimen

Retention: SAMPLES WITH DNA

Stool samples, serum, plasma, liver and (only in the obese patients) adipose tissue

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Liver Extracts

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tissue Extracts; Complex Mixtures

Study Officials

• Stefano Ginnani Corradini, MD, PhD

  Department of Translational and Precision Medicine, "Sapienza", University of Rome

  STUDY DIRECTOR

• Fredrik Backhed, PhD

  Wallenberg laboratoriet, Gotebörg, Sweden

  STUDY DIRECTOR

• Frida Leonetti, MD, PhD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

• Gianfranco Silecchia, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

• Francesco Gossetti, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

• Adriano De Santis, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

• Claudio Di Cristofano, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 4, 2014
• First Posted: June 6, 2014
• Study Start: November 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2017
• Last Updated: November 20, 2020

Record last verified: 2020-11

Locations

IT (1)