Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2019; 25(4): 509-520
Published online Jan 28, 2019. doi: 10.3748/wjg.v25.i4.509
Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease
Marco Biolato, Fiorella Manca, Giuseppe Marrone, Consuelo Cefalo, Simona Racco, Giacinto A Miggiano, Venanzio Valenza, Antonio Gasbarrini, Luca Miele, Antonio Grieco
Marco Biolato, Giuseppe Marrone, Simona Racco, Giacinto A Miggiano, Antonio Gasbarrini, Luca Miele, Antonio Grieco, Department of Gastroenterological, Endocrine-Metabolic and Nefro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
Fiorella Manca, Giacinto A Miggiano, Antonio Gasbarrini, Luca Miele, Institute of Special Medical Pathology and Medical Semeiotics, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Consuelo Cefalo, Antonio Grieco, Institute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Venanzio Valenza, Department of Image Diagnostics, Oncological Radiotherapy and Hematology Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
Venanzio Valenza, Nuclear Medicine Institute, Università Cattolica del Sacro Cuore, Rome 00168, Italy
Author contributions: Grieco A was the guarantor and designed the study. Biolato M, Marrone G, Cefalo C and Racco S participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript. Manca F and Miggiano GA designed the diets and managed all the nutritional aspects of the study. Valenza V performed intestinal permeability tests. Gasbarrini A and Miele L revised the article critically for important intellectual content.
Supported by the Italian Ministry of Education, University and Research (MIUR), scientific research programs of relevant national interest year 2010-2011, No. 2010C4JJWB.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Catholic University of Sacred Heart (Rome, Italy).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
STROBE statement: The authors have checked the manuscript according to STROBE checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Marco Biolato, MD, PhD, Staff Physician, Liver Transplant Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, Rome 00168, Italy. marco.biolato@policlinicogemelli.it
Telephone: +39-6-30154469
Received: November 5, 2018
Peer-review started: November 5, 2018
First decision: December 20, 2018
Revised: January 14, 2019
Accepted: January 18, 2019
Article in press: January 18, 2019
Published online: January 28, 2019
Processing time: 83 Days and 17.3 Hours
ARTICLE HIGHLIGHTS
Research background

In patients with non-alcoholic fatty liver disease (NAFLD), intestinal permeability is increased, promoting translocation of bacteria-derived products into the portal circulation and increasing hepatic exposure to injurious substances that stimulate hepatic inflammation and fibrosis. In animal models, adaptation of a high-fat diet or high-fructose intake has been associated with increased gut permeability and metabolic endotoxiemia

Research motivation

Although diet can significantly influence intestinal permeability, clinical studies investigating the effects of dietary interventions on the intestinal permeability of NAFLD patients are lacking. The Mediterranean diet contains a high intake of mono- and polyunsaturated fatty acids, fibres, polyphenols, antioxidants and phytochemicals; many of these components promote short-chain fatty acid-producing gut bacteria and have significant prebiotic effects. As such, we hypothesized a therapeutic effect of the Mediterranean diet for reducing impaired intestinal permeability in patients with NAFLD.

Research objectives

Aim of the study is to detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.

Research methods

Patients underwent a dietary treatment via a crossover design lasting 48 wk: 16-wk of a Mediterranean diet, 16-wk of a free wash-out diet and 16-wk of a low-fat diet. Intestinal permeability was evaluated at baseline and at the end of each diet period using the validated method of urinary excretion of chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA). 51Cr-EDTA excretion is a good indicator of the severity of gut-mucosal inflammation and loss of tight junctions.

Research results

Patients with NAFLD experienced a significant reduction in body weight, waist circumference and transaminase levels after 16 wk of a Mediterranean diet. Seventy percent of patients had intestinal permeability alteration at baseline, but no significant changes in intestinal permeability were observed at the end of the Mediterranean diet period or at the end of the low-fat diet period.

Research conclusions

The Mediterranean diet is a safe and effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD, thereby confirming that it should be the first step in a treatment program. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.

Research perspectives

In our view, the modulation of intestinal permeability in humans is much more difficult to obtain than in animal models. We ask ourselves whether our result could be modified with a different duration of the observation and of the diet program.