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

To investigate the adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture model.


For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at “regular”, double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy, and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFα and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to colonoscopy.


In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFα and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo experiment, LGG was detectable only in the colon of patients who consumed the LGG formulation, and bowel cleansing did not affect LGG adhesion. UC patients who consumed the double LGG dose had increased mucosal concentrations of the bacteria and reduced TNFα and IL-17 expression compared with patients who consumed the regular dose (48% and 40% reduction, respectively, P < 0.05).


In an ex vivo organ culture model, LGG showed consistent adhesion and anti-inflammatory effects. Colonization by LGG after consumption for a week was demonstrated in vivo in the human colon. Increasing the administered dose increased the adhesion and effectiveness of the bacteria. For the first time, we demonstrated that LGG effectively adheres to the colonic mucosa and exerts anti-inflammatory effects, both ex vivo and in vivo.

Keywords: Lactobacillus rhamnosus GG, Ulcerative colitis, Probiotic, Adhesion, Cytokines

Core tip: Since probiotic utilization is often driven by unproven health claims, we intended to explore the feasibility and effectiveness of a safe and well-characterized probiotic bacterial species, the Lactobacillus rhamnosus GG (LGG), in ulcerative colitis (UC) patients, through a preclinical proof-of-concept study. We demonstrated for the first time effective mucosal colonization and the anti-inflammatory effect of LGG, both ex vivo and in vivo, by quantifying bacterial DNA and cytokine RNA expression directly at the mucosal site using genomic techniques. Further translational and clinical studies would confirm the utility and optimize the therapeutic administration of LGG in UC patients.