Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study

AIM To investigate the adhesion and anti-inflammatory effects of Lactobacil us 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.METHODS 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.RESULTS 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).CONCLUSION 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 antiinflammatory effects, both ex vivo and in vivo.

Probiotics in inflammatory bowel disease: Pathophysiological background and clinical applications

Ulcerative colitis and Crohn's disease, collectively termed the inflammatory bowel diseases(IBD), are chronic inflammatory disorders of the gastrointestinal tract. A "dysbiotic" relationship between the commensal gut flora and the intestinal mucosa-associated immune system has been at the core of the pathogenesis of these conditions. Probiotics are "good bacteria" with the ability to benefit the health of the host and their therapeutic application has been studied in IBD. The theoretical basis for such utilization relies upon the ability of probiotic microorganisms to interfere with the dysregulated homeostasis that takes place in IBD and restore the immune-bacterial interaction at the intestinal mucosa. Proposed mechanisms of action include the reconstitution of altered flora composition, enhancement of the integrity of the epithelial barrier, promotion of tolerogenic action by dendritic cells, strengthening of the defensive mechanisms of the innate immunity, and the suppression of pro-inflammatory adaptive immune responses. Despite this abundance of supporting experimental evidence, clinical application of probiotics in IBD has been disappointing. Possible explanations for such discrepancy include the great diversity of microorganisms that fall under the definition of probiotics, the lack of standardization of dosages and administration schemes, the heterogeneity between clinical trials, and the inclusion in the treatment arms of patients with a large variety of clinical phenotypes. Addressing these important issues will be critical for the optimal usage of probiotic-based therapies for patients with IBD.

Is proliferative colonic disease presentation changing?

AIM:To compare the site,age and gender of cases of colorectal cancer(CRC) and polyps in a single referral center in Rome,Italy,during two periods.METHODS:CRC data were collected from surgery/pathology registers,and polyp data from colonoscopy reports.Patients who met the criteria for familial adenomatous polyposis,hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study.Overlap of patients between the two groups(cancers and polyps) was carefully avoided.Theχ 2 statistical test and a regression analysis were performed.RESULTS:Data from a total of 768 patients(352 and 416 patients,respectively,in periods A and B) who underwent surgery for cancer were collected.During the same time periods,a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies(428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B).A proximal shift in cancer occurred during the latter years for both sexes,but particularly in males.Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio(OR) 3.31,95%CI:2.00-5.47;P < 0.0001).A similar proximal shift was observed for polyps,particularly in males(OR 1.87,95%CI:1.23-2.87;P < 0.0038),but also in females(OR 1.62,95%CI:0.96-2.73;P < 0.07).CONCLUSION:The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade,particularly in males.

A case of oesophageal ulcer developed after taking homeopathic pill in a young woman

食道的溃疡主要由于胃食道的倒流疾病(GERD ) 发生。然而，导致药片的食道的溃疡是一个相当普通的事件。损害主要由于药片或它它的化学作文的陷阱。这份病案报告描述食道的粘膜溃疡在没有食道的混乱的以前的历史并且收到了同种疗法的药的一个健康 35 年的老妇人发生了。现在的盒子表明药片陷阱能甚至在健康年轻个人的食道发生，那食道的粘膜溃疡能被通常任何潜在地粘膜的好攻击的效果认为缺乏的物质触发。

“Mucosal healing” in ulcerative colitis:Between clinical evidence and market suggestion

In recent decades,the prominent role of endoscopy in the management of ulcerative colitis(UC)has been translated into the concept of mucosal healing(MH)as a fundamental therapeutic end-point.This is partially the consequence of growing evidence of a positive prognostic role of MH on the disease course and partially due to market cues indicating a higher rate of MH in patients treated by novel potent biologic agents.The aim of the present review is to clarify the current knowledge of MH in UC,analyzing the definition,the putative prognostic role and the association of MH with the current drugs used to treat UC patients.Because solid data about the management of UC patients based solely on the healing of the mucosa are not yet available,a tailored approach for individual patients thatconsiders the natural history of UC and the presence of prognostic indicators of aggressive disease is desirable.Consequently,unnecessary examinations and treatment would be avoided and restricted to UC patients who require the maximum amount of effort to affect the disease course in the short and long term.