Probiotics in infective diarrhoea and inflammatory bowel diseases

Bacteria are present throughout the gastrointestinal tract, but their pattern and concentration vary greatly. Probiotics are living organisms that supply beneficial health effects to the host. So far the beneficial effects of probiotics have been shown, almost exclusively, under poorly defined experimental conditions. There are little convincing data from well-designed, double-blind controlled trials supporting health-promoting effects. The use of probiotics to treat gastrointestinal infections has produced contrasting results. Apart from information on rotavirus infection in children, there is no convincing evidence from controlled studies on the efficacy of probiotics in the prevention or treatment of infective diarrhoea. However, experimental and clinical studies suggest that there are potential therapeutic roles for probiotics in the treatment of inflammatory bowel diseases. This review focuses on the available data concerning the mechanisms of action of probiotics, and on the results from clinical studies using probiotics to treat infective diarrhoea and inflammatory bowel disease.     

Original research: National survey evaluating the provision of gastroenterology dietetic services in England

AimsThe aim of the study was to assess the provision of dietetic services for coeliac disease (CD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).MethodsHospitals within all National Health Service trusts in England were approached (n=209). A custom-designed web-based questionnaire was circulated via contact methods of email, post or telephone. Individuals/teams with knowledge of gastrointestinal (GI) dietetic services within their trust were invited to complete.Results76% of trusts (n=158) provided GI dietetic services, with responses received from 78% of these trusts (n=123). The median number of dietitians per 100 000 population was 3.64 (range 0.15–16.60), which differed significantly between regions (p=0.03). The most common individual consultation time for patients with CD, IBS and IBD was 15–30 min (43%, 44% and 54%, respectively). GI dietetic services were delivered both via individual and group counselling, with individual counselling being the more frequent delivery method available (93% individual vs 34% group). A significant proportion of trusts did not deliver any specialist dietetic clinics for CD, IBS and IBD (49% (n=60), 50% (n=61) and 72% (n=88), respectively).ConclusionThere is an inequity of GI dietetic services across England, with regional differences in the level of provision and extent of specialist care. Allocated time for clinics appears to be insufficient compared with time advocated in the literature. Group clinics are becoming a more common method of dietetic service delivery for CD and IBS. National guidance on GI dietetic service delivery is required to ensure equity of dietetic services across England.     

Review: Constipation in ulcerative colitis: pathophysiology and practical management

Clinical experience suggests that there is a cohort of patients with refractory colitis who do have faecal stasis that contributes to symptoms. The underlying physiology is poorly understood, partly because until recently the technology to examine segmental colonic motility has not existed. Patients are given little information on how proximal faecal stasis can complicate colitis. Treatment guidelines are scanty and many patients are offered little apart from laxatives and advice on increasing fibre intake, which often makes symptoms worse. This article aims to review the history, pathology and management, and create impetus for future research on this underappreciated condition.     

Development of gastroenterology in Bangladesh

Diseases of the gastrointestinal tract and liver are very common in Bangladesh. Gastroenterology as a dedicated specialty was initiated in 1977 at the Institute of Postgraduate Medicine and Research in Dhaka. One more centre was set up later and these centres are providing specialized diagnostic and therapeutic services. These centres are also imparting training in endoscopy and 49 endoscopists trained so far are providing services in 22 centres around the country. Clinical gastroenterologists are also being trained in a 3 year Master's degree course and three specialists have already completed this. A Gastroenterology Society was formed in 1988 and has held three national scientific conferences and 20 regional meetings. Research in special problems of the country has also been initiated and work on aspects of peptic ulcer disease, chronic calcific pancreatitis and chronic viral hepatitis has been conducted. The demand for gastrointestinal services is high and the specialty has attracted a good number of young doctors. Gastroenterology is likely to grow in size and quality in Bangladesh.     

Colonization of microflora in mice: mucosal defense against luminal bacteria

To investigate the pathogenesis of inflammatory bowel disease, it is critical to develop a system that uses simple and reproducible models for analyzing the "normal" mucosal defense mechanism. In the present study, germ-free mice were conventionalized by the oral administration of microorganisms prepared from the feces of genetically identical mice. Histological assessment and mucin characterization of small intestine and colon were then carried out. Histological findings in the gut were site-dependent and clearly time-dependent. Acute inflammation was most evident in the cecum. The cecal mucosa exhibited hyperplastic changes in epithelial cells, infiltration of polymorphonuclear cells, crypt abscesses, and epithelial projections on the epithelial surface 7 days after conventionalization. Some of the changes were similar to those seen in human ulcerative colitis. The histological findings in the conventionalized mice were comparable to those in specific pathogen-free mice after 28 days. Mucin histochemistry revealed that bacterial colonization altered the number of rectal goblet cells and the mucin composition in a time-dependent fashion. Although this model shares only some characteristics of human inflammatory bowel disease, it is unique in demonstrating the acquisition of mucosal defense. Understanding of this process is critical for the elucidation of inflammatory bowel disease pathogenesis. (Received Apr. 28, 1998; accepted July 24, 1998)     

Ultrasound in gastroenterology

Crohn’s disease (CD) is an inflammatory bowel disease whose precise etiology is still unknown, and therefore a causal therapy is not yet available. Studies showing the overexpression of IL-12 and IL-23, polymorphisms in genes encoding those cytokines and their receptors and genome-wide association studies have linked Crohn’s pathogenesis with IL-12/23 pathway. Ustekinumab is a novel therapeutic IgG₁ kappa monoclonal antibody that modulates Th1 and Th17 function, by blocking the p40 subunit of both IL-12 and IL-23 and preventing the interaction with their receptors on T cells, natural killer cells and antigen-presenting cells with established efficacy in psoriasis. This review will mainly focus on the available evidence on the role of ustekinumab in moderate-to-severe CD. The potential role of this biologic in the armamentarium of CD therapy is discussed.     

Endoscopic luminal stenting: Current applications and future perspectives

Endoscopic luminal stenting(ELS) represents a minimally invasive option for the management of malignant obstruction along the gastrointestinal tract. Previous studies have shown that ELS can provide rapid relief of symptoms related to esophageal, gastric, small intestinal, colorectal, biliary, and pancreatic neoplastic strictures without compromising cancer patients’ overall safety. As a result, in both palliative and neoadjuvant settings, ELS has largely surpassed radiotherapy and surgery as a ...     

Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis

Objective Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC). Materials and methods A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled. Results Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p?=?0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p?=?0.0014), and nocturnal diarrhoea in 28% versus 18% (p?=?0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p?=?0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients. Conclusions Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation ‘microscopic’. Our study confirms the strong association with coeliac disease.     

Recommendations for Improved Use of the Murine TNBS-Induced Colitis Model in Evaluating Anti-inflammatory Properties of Lactic Acid Bacteria: Technical and Microbiological Aspects

Probiotic bacteria have been shown to exert promising beneficial effects in different types of intestinal disorders, including chronic inflammation. In this context, animal models of inflammatory bowel disease are useful in studying the possible prophylactic role of candidate probiotic strains. This study aimed at evaluating the critical technological and microbiological parameters as well as the robustness of the murine trinitrobenzene sulfonic acid (TNBS)–induced model of colitis, after intragastric administration of lactic acid bacteria (LAB) preparations. A standardized methodology was applied to assess the protective effect achieved by various bacterial concentrations and culture conditions of the reference strain Lactobacillus plantarum NCIMB 8826. Not only was protection found to vary in function in different levels of colitis, but also repeated experiments showed a clear bacterial dose-dependent attenuation of colitis. The physiological stage of bacteria was shown to impact as well, with substantial, mild, or reduced improvement of inflammatory scores for exponentially growing, stationary-phase, or killed bacteria, respectively. A recombinant strain, secreting murine interleukin-10 (IL-10) and previously reported to successfully treat colitis in two different models of murine colitis (dextran sulfate sodium [DSS] and IL-10-deficient mice), was used to validate the final experimental conditions. In conclusion, we identified and optimized some of the key parameters that need to be controlled in order to ensure reliable comparison of results generated over a long period of time or independent experiments. The recommendations for an improved model presented here will prove to be helpful for reproducible, independent comparison of the anti-inflammatory potential of wild-type or recombinant candidate probiotic strains, whether administered as pure cultures or as blends.     

Inflammatory bowel disease masquerading as traveller's diarrhoea

Diarrhoea that occurs during or after recent travel is predominantly infectious in nature; however, in atypical or prolonged cases a broader range of aetiologies for diarrhoea must be considered, and a careful history and examination may reveal clues to more sinister causes of diarrhoea. We report two cases in which a recent travel history and a positive stool culture or polymerase chain reaction testing for bacterial pathogens delayed the diagnosis of ulcerative colitis. As a result of severe inflammatory bowel disease, colectomy was the final result in both cases. Early consideration of causes other than infection for traveller's diarrhoea may prevent unnecessary morbidity in young patients.     

Scandinavian epidemiological research in gastroenterology and hepatology

Abstract

In the last decades, a large number of epidemiological studies in gastroenterology and hepatology have originated from the Scandinavian countries. With the help of large health databases, with good validity and other registries related to patient outcomes, researchers from the Scandinavian countries have been able to make some very important contributions to the field. These countries, Sweden, Norway, Finland, Denmark and Iceland, have all universal access to health care and have shown to be ideal for epidemiological research. Population-based studies have been frequent and follow-up studies have been able to describe the temporal trends and changes in phenotypes. Our ability in Scandinavia to follow up defined groups of patients over time has been crucial to learn the natural history of many gastrointestinal and liver diseases and often in a population-based setting. Patient-related outcomes measures will probably gain increasing importance in the future, but Scandinavian gastroenterologists and surgeons are likely to have a better infrastructure for such endeavors compared to most other populations. Thus, there is a bright future for international competitive research within the field of gastrointestinal and liver diseases in Scandinavia.     

Emerging role of calprotectin in gastroenterology

Calprotectin is a calcium and zinc binding protein of the S100 family derived predominantly from neutrophils and monocytes. It is detectable in body fluids and tissue samples and is emerging as a valuable marker in the diagnosis, and the monitoring and determining of the prognosis of commonly encountered gastroenterological conditions. Fecal calprotectin, in particular, has for a long time been regarded as a promising marker of gastrointestinal pathology and has now been established as a routine test in Norway and at several centers in the UK.     

Protective effects of cathelicidin-encoding Lactococcus lactis in murine ulcerative colitis

Background and Aim: Intrarectal administration of mouse cathelin‐related antimicrobial peptide (mCRAMP) reduced intestinal inflammation in mice. In the current study, we examined whether mCRAMP‐transformed Lactococcus lactis given orally attained similar protective effects. Method: mCRAMP was produced and secreted from the transformed L. lactis. Murine colitis was induced by ingestion of 3% dextran sulfate sodium (DSS) for 7 days. Eight or 10 log colony forming unit (cfu) L. lactis or the transformed strains with or without nisin induction were given orally as a parallel treatment with DSS. The body weight, fecal microbiota populations, clinical symptoms and histological examinations of colonic tissues were determined. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) level were also evaluated to reflect the degree of inflammation. A prototype anti‐inflammatory drug sulfasalazine was used as a reference drug to compare the efficacy and mechanisms of action for ulcerative colitis (UC). Result: Compared with the control group with colitis, cathelicidin‐transformed L. lactis could improve the clinical symptoms, maintain crypt integrity and preserve mucus content (P < 0.01). The number of apoptotic cells, MPO activity and MDA level were also significantly reduced (P < 0.05). The increases of fecal microbiota in colitis animals were markedly prevented (P < 0.001). Unlike mCRAMP‐encoding L. lactis, effective doses of sulfasalazine only alleviated the clinical symptoms (P < 0.01) but not the mucosal damage in the colon. Conclusion: mCRAMP‐transformed L. lactis has been shown to produce mCRAMP, effectively preventing murine UC. Oral administration of this biological preparation is better than sulfasalazine for the treatment of UC.     

Prospect of gastroenterology and hepatology in the next century

Subjectheadingsgastroenterology;hepatology;nextcenturyThetaskofpredictingwhatGastroenterologyandHepatologymaylooklikeinthecobingcenturyisagreatPersonalchallengeandatthesametimeanaweinspiringassignment.NotofilyhavethesetwomedicalspecialtiesbecomeverylargeanddiversifiedbuttherearesomanynewdiscoveriesandideasthatitisacapriciousundertakingtOattemptfore-tellingwhichofthemmaybecomepaftoftheneXtcensely'smedicalpractice.Ithereforewilltakethepersonalprivilegeofbeinghighlyselective,choosingonlytopicsf…     

Effect of Lactobacillus plantarum LP-Onlly on gut flora and colitis in interleukin-10 knockout mice

Background and Aim: Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine the effects of probiotic Lactobacillus plantarum LP‐Onlly (LP) on gut flora and colitis in interleukin‐10 knockout (IL‐10^?/?) mice, a model of spontaneous colitis. Methods: IL‐10^?/? and wild‐type mice were used at 8 weeks of age and LP by gavage was administered at a dose of 10⁹ cells/day per mice for 4 weeks. Mice were maintained for another one week without LP treatment. The colonic tissues were collected for histological and ultrastructural analysis at death after 4 weeks treatment of LP, and the feces were collected at 1‐week intervals throughout the experiment for the analysis of gut flora and LP using selective culture‐based techniques. Results: Compared with control mice, IL‐10^?/? mice developed a severe intestinal inflammation and tissue damage, and had an abnormal composition of gut microflora. LP administration attenuated colitis with the decreased inflammatory scoring and histological injury in the colon of IL‐10^?/? mice. In addition, LP administration increased the numbers of beneficial total bifidobacteria and lactobacilli, and decreased the numbers of potential pathogenic enterococci and Clostridium perfringens, although the decrease of coliforms was not significant after LP treatment in IL‐10^?/? mice. Conclusions: Oral administration of LP was effective in the treatment of colitis, with the direct modification of gut microflora in IL‐10^?/? mice. This probiotic strain could be used as a potential adjuvant in the therapy of inflammatory bowel disease, although further studies are required in human.     

Clinical therapeutic effects of probiotics in patients with constipation associated with Parkinson disease: A protocol for systematic review and meta-analysis

Background:Constipation is the most predominant symptom of Parkinson disease (PD), preceding the occurrence of motor symptoms in some patients, leading to reduced quality of life (QOL). The general approaches for the treatment have some side effects, but probiotics are live or attenuated microorganisms attributed to ameliorating constipation effects. Moreover, as treatments are generally well tolerated and side effects are scarce, there is room for further research. Therefore this work aims at investigating the clinical effectiveness and safety of probiotics for constipation in PD.Methods:Published RCTs will be retrieved by searching Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wan Fang database, and China Biology Medicine Database (complete bowel movement), which will be searched from establishment of the database to October 10, 2021. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines are used to design this protocol. RevMan V.5.3 software will be used for meta-analysis, risk of bias will be assessed by the Cochrane Collaboration tool and the collected evidence will be narratively synthesized. We will also perform a meta-analysis to pool estimates from studies considered to be homogenous. Subgroup analyses will be based on intervention or overall bias.Conclusion:The meta-analysis will assess the effectiveness and safety of using probiotics to treat and heal the constipation of PD.Ethics and dissemination:Ethics approval is unrequired.Registration number:CRD42021276215.     

Targeting T‐cell migration in inflammatory bowel disease

Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract and are collectively referred to as inflammatory bowel disease (IBD). IBD is a major cause of lifetime morbidity, has a severe impact on quality of life of patients (equivalent to that of rheumatoid arthritis, asthma, migraine or diabetes) and constitutes a substantial economic burden to the healthcare system. The introduction of anti‐tumour necrosis factor (TNF) antibodies has dramatically improved the treatment of IBD, but approximately one‐third of patients are nonresponders and another 30–50% will eventually lose the therapeutic effect or become intolerant to these antibodies. Thus, there is an urgent and unmet need for new therapies. The aetiologies of the different forms of IBD have not been fully elucidated but there is strong evidence implicating T cells and T‐cell migration to the gut in initiating and perpetuating the intestinal inflammatory process and tissue destruction. In recent years, progress in basic science has shed light on the mechanisms regulating T‐cell migration to the gut and new therapeutics targeting these pathways have been developed. It is interesting that some of the factors directing the localization of T cells to the gut have been shown to be relatively organ specific, potentially enabling new T‐cell‐targeted treatments to demonstrate improved safety whilst preserving therapeutic efficacy. Here, fundamental aspects of the gut immune system, the generation of tissue‐tropic effector T cells and the mechanisms of T‐cell trafficking to the gut mucosa will be reviewed. In addition, the role of these processes in IBD and how they have been exploited for the development of novel therapies for IBD will be discussed.