Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2018; 24(41): 4652-4662
Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4652
Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study
Cristiano Pagnini, Vito Domenico Corleto, Michela Martorelli, Claudio Lanini, Giancarlo D’Ambra, Emilio Di Giulio, Gianfranco Delle Fave
Cristiano Pagnini, Vito Domenico Corleto, Michela Martorelli, Claudio Lanini, Giancarlo D’Ambra, Emilio Di Giulio, Gianfranco Delle Fave, Department of Digestive and Liver Disease, School of Medicine and Psychology, S. Andrea Hospital, Sapienza University, Rome 00189, Italy
Author contributions: Pagnini C designed the study, performed experiments, interpreted the data and wrote the paper; Corleto VD collected samples and edited the paper; Martorelli M and Lanini C performed the majority of the experiments; D’Ambra G and Di Giulio E collected samples and coordinated the research; and Delle Fave G designed the study, coordinated the research and edited the paper.
Institutional review board statement: This study was approved by the institutional review board of S. Andrea Hospital.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
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:
Correspondence to: Cristiano Pagnini, MD, PhD, Department of Gastroenterology and Digestive Endoscopy, S. Giovanni Addolorata Hospital, Via dell’ Amba Aradam 9, 00184 Rome, Italy.
Telephone: +39-6-77051 Fax: +39-6-77053253
Received: July 19, 2018
Peer-review started: July 19, 2018
First decision: August 25, 2018
Revised: September 28, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 7, 2018
Research background

Ulcerative colitis (UC) is one of the two major forms of Inflammatory bowel disease (IBD), and it is characterized by a deregulated inflammation of the intestinal mucosa clinically presenting with symptoms of diarrhea and bloody stools. Despite different therapies are available, still many patients do not adequately respond. The therapeutic application of probiotic bacteria in this setting could represent an efficient and attractive option for UC patients.

Research motivation

The research of probiotic application in IBD has been largely focused on in vitro systems and experimental models, and pre-clinical and clinical studies are characterized by an extreme dishomogeneity. Therefore, no specific indications for therapeutic application of probiotics (which probiotic species, doses, duration of therapy, and kind of UC disease severity/extension to treat) can be extrapolated from the literature.

Research objectives

In order to overcome the consistent dishomogeneity of previous studies, the purpose of the present work was to restrict the investigation of a well characterized probiotic species, Lactobacillus rhamnosus GG (LGG), in a specific clinical setting (mild- moderate UC patients), to measurable parameters correlated with the potential therapeutic effect (mucosal adhesion and anti-inflammatory effect).

Research methods

We intended to investigate the adhesion and effect of LGG directly at the mucosal site by using modern genomic culture-independent techniques. An ex-vivo experimental model based on short-term biopsies organ culture was developed. Concentration and mucosal effect of LGG in colonic mucosa was then confirmed in vivo in UC patients and normal subjects after consumption of oral formulation containing LGG.

Research results

LGG affectively adhered to the colonic mucosa, both in the experimental model and in vivo. Moreover, the probiotc administration reduced expression of two important pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-17). Higher mucosal concentration of the bacteria and more consistent reduction of pro-inflammatory cytokines has been observed increasing the dose of LGG.

Research conclusions

The present study demonstrated for the first time that LGG affectively adheres to the colonic mucosa and exerts anti-inflammatory effect, both ex vivo and in vivo. Moreover, we demonstrated a potential increasing of effect with higher dose of probiotic. Considering that probiotic utilization in clinical setting is often empirical and not evidence-based, the present study can put the basis for the evaluation of LGG in the setting of UC with specific clinical trials.

Research perspectives

Utilization of appropriate experimental models appears crucial for the design of pre-clinical studies. Translational medicine studies, with both experimental and in vivo experiments, may contribute to correctly investigate potential novel treatments, and in particular to evaluate the potential application of LGG and other probiotic bacteria for the treatment of UC and other inflammatory conditions.