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Patients with Barrett's esophagus (BE) are at risk of progression esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with non-dysplastic BE (NDBE).A longitudinal study in three referral centers, performed between January 2010 and-December 2019. As progression to LGD can be considered as indication for ablative therapy, the study endpoint was histopathologic progression to LGD, HGD or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and remaining 30% for internal validation.A total of 542 patients were included, 69.4% males, mean age 62.2 years. Long segment BE at index endoscopy was diagnosed in 20.8% of the patients. After mean follow up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified neutrophil to lymphocyte ratio (NLR, OR 2.08, 95% confidence interval, CI, 1.77-2.32, p0.001), BE length (OR 1.22, 95% CI 1.09-1.36, p0.001), age (OR 1.03, 95% CI 1.02-1.05, p=0.02), smoking (OR 1.66, 95% CI 1.09-2.75, p=0.04) and renal failure (OR 1.51. 95% CI 0.93-2.43, p=0.07) as predictors of histologic progression at 3 years. The area under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohort, respectively.This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhance patient selection for more intense surveillance programs.

This study evaluated the prevalence of cardiovascular risk-factors in patients with mesenteric panniculitis.To determine whether cardiovascular risk-factors and mesenteric panniculitis are associated.Retrospective, matched case-control study of patients referred to Meir Medical Center, Israel, 2014-2019, who underwent computerized tomography scan, were diagnosed mesenteric panniculitis by radiologic criteria. They were compared to two, matched case-control groups: hospitalized patients without mesenteric panniculitis and the general population based on Israeli Ministry of Health surveys. Patients with active malignancy, IBD or significant intra-abdominal morbidity were excluded.Of 376 patients with mesenteric panniculitis diagnosed by computerized tomography, 187 were included. Compared to hospital patients, they had higher incidence of dyslipidemia (77.5%/56.7%), hypertension (52.4%/40.6%), obesity (body mass index30) (60.4%/30.5%) and nonalcoholic fatty liver disease (42.2%/16.6%). Similar differences were observed compared to the general population. In multivariable logistic regression, dyslipidemia, obesity, and nonalcoholic fatty liver disease were independent predictors for mesenteric panniculitis.Patients with mesenteric panniculitis have more cardiovascular risk-factors compared to a case-control group and to the general population. This suggests that mesenteric panniculitis is clinically significant and may be part of the metabolic morbidity burden. This association should be further explored.

BACKGROUND: Cannabis benefits patients with inflammatory bowel disease (IBD). Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts. Mucosal healing (MH) requires epithelial layer restoration. OBJECTIVE: To analyze the effects of CB2 agonist on parameters implicated in gut inflammation and MH. METHODS: Mucosal samples from areas of inflamed/uninflamed colon from 16 patients with IBD were cultured without/with cannabinoid receptor 2 (CB2) agonist (JWH-133, 10 µM, 6 hours (hr)), and analyzed for epithelial/stromal cell proliferation, apoptosis (secretome matrix metalloproteinase 9 (MMP9) activity, which impairs epithelial permeability) and interleukin-8 (IL-8) levels (n = 5–9). In addition, Caco-2 (colon carcinoma epithelial cells) were cultured with biopsy secretomes (48 hr), and analyzed for phenotype and protein markers of proliferation (proliferating cell nuclear antigen), autophagy (LC3IIB) and permeability (Zonula occludens-1) (n = 4–6). RESULTS: Uninflamed tissue had higher epithelial proliferation (Ki67: 50%↑, p 50%↓, p

Background and aims The primary clinical characteristics of Fanconi Anemia (FA) include typical physical features, progressive bone marrow failure, and an increased incidence of neoplasms, including esophageal carcinoma. Currently, there are no data regarding endoscopic findings or the interval time to malignancy in these patients. Data about the contribution of Human Papilloma Virus (HPV) to esophageal carcinoma is conflicting. Our objective is to document the upper gastrointestinal (GI) findings at baseline, document cancer incidence, and evaluate the role of HPV among these cancers. Methods We reviewed endoscopic and clinical data of FA subjects who participated in active surveillance before cancer diagnosis. Incident esophageal cancers were stained for HPV p16 protein. Results Eight FA patients were included (men 62.5%; median age at first endoscopy 20 years, median endoscopies number: 5.5). At baseline, 8/8 had endoscopic evidence for reflux esophagitis. In 3/8 the reflux esophagitis was mild and in 5/8 it was moderate or severe. During the follow up time (median time 4.5 years 2/8 developed Barrett’s esophagus and 2/8 patients had incident esophageal squamous cell carcinoma during follow up, at intervals of eight and eighteen months from the previous upper endoscopy. Both cancers stained negative for HPV P16. Conclusions FA subjects have both an extremely high risk for esophageal cancer within short intervals and a very high prevalence of reflux esophagitis with various severities. Active surveillance programs in specialized centers including annual upper endoscopies should be considered in these patients.

The digestive tract can be targeted by SARS-CoV-2 and its interactions with the immune system, and the lungs may have meaningful implications in the pathogenesis of COVID-19. This gastrointestinal involvement needs to be considered in clinical practice., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a direct impact on the gastrointestinal system, as up to 50% of fecal samples from coronavirus disease 2019 (COVID-19) patients contain detectable viral RNA despite a negative rhino-pharyngeal swab. This finding, together with an intestinal expression of angiotensin conversion enzyme 2 protein, suggests a possible fecal-oral transmission for SARS-CoV-2. Furthermore, gastrointestinal (GI) symptoms are common in COVID-19 patients including watery diarrhea, vomiting—particularly in children—nausea, and abdominal pain. Pathogenesis of SARS-CoV-2 infection presents significant similarities to those of some immune-mediated diseases, such as inflammatory bowel diseases or rheumatoid arthritis, leading to the hypothesis that targeted therapies used for the treatment of immune-mediated disease could be effective to treat (and possibly prevent) the main complications of COVID-19. In this review, we synthesize the present and future impact of SARS-CoV-2 infection on the gastrointestinal system and on gastroenterology practice, hypothesizing a potential role of the “gut-lung axis” and perhaps of the gut and lung microbiota into the interindividual differential susceptibility to COVID-19 19 disease. Finally, we speculate on the reorganization of outpatient gastroenterology services, which need to consider, among other factors, the major psychological impact of strict lockdown measures on the whole population.

OBJECTIVE Use of medical cannabis for improving symptoms of inflammatory bowel disease is increasing. However, reports on long-term outcomes are lacking. This prospective, observational study assessed the effects of licensed cannabis use among patients with inflammatory bowel disease. METHODS Dose and mode of consumption, adverse events, use of other medications, and long-term effects were evaluated among 127 patients with inflammatory bowel disease using legalized medical cannabis. Blood count, albumin, and C-reactive protein were assessed before, 1 month, and at least 1 year after medical cannabis therapy was initiated. Questionnaires on disease activity, patient function, and signs of addiction were completed by patients and by a significant family member to assess its effects. RESULTS The average dose used was 31 ± 15 g/month. The average Harvey-Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001) during a median follow-up of 44 months (interquartile range, 24-56 months). There was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74% (P < 0.05). We conclude that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients' social or occupational status. CONCLUSIONS Cannabis use by inflammatory bowel disease patients can induce clinical improvement and is associated with reduced use of medication and slight weight gain. Most patients respond well to a dose of 30 g/month, or 21 mg Δ9-tetra- hydrocannabinol (THC) and 170 mg Cannabidiol (CBD) per day.

Background Current inflammatory bowel disease (IBD) therapies are highly effective. However, compliance with treatment is influenced by patients’ perception of benefits versus risks. Understanding these perceptions and their influence on patients’ treatment decision-making is crucial for achieving compliance, especially during Covid-19 pandemic. Aim: to assess patients’ perception of risks of IBD exacerbation and SARS-CoV-2 infection, and their influence on patients’ decisions regarding biologic and immunosuppressive treatments during Covid-19 pandemic in Israel. Methods A prospective internet-based survey among Meir Medical Center, IBD clinic patients. Results 116 patients have responded. Mean age 42 (18–84), 44 (38%) males, 75 (64%) Crohn’s disease, 38 (32%) ulcerative colitis, 34 (29%) with history of abdominal surgery, 47 (40%) were in remission and 9(7.5%) with severe disease. 18 (15%) patients were on Immunosuppressive and 76 (66%) on biologic treatments. Concerns of contracting SARS-CoV-2 infection: 56 (48%) patients considered their risk as equal to that of the general population whereas 53 (46%) considered it to be increased. 55% of the patients related the increase risk of COVID-19 infection to their IBD treatment, whereas 47% related it to having IBD. Patients treated with biologics were more concerned of becoming infected with SARS-CoV-2 then those who were not. There was also a significant association between depression and anxiety levels and the fear of becoming infected (r= 0.3 for depression and 0.4 for anxiety). Adherence to IBD treatment: Only 8 (7.5%) patients considered stopping their IBD treatment, and only 4 (3.7%) patients actually stopped their treatment. Patients with more severe disease were more inclined to stop their treatment compared to those with mild disease. Reasons for not stopping treatment were fear of disease exacerbation in 37 (32%) patients, and reassuring information received from medical providers, in 25 (21.5%) patients. When faced with a theoretical question of trading long-term remission versus risk of SARS-CoV-2infection, 34 (29%) patients were willing to accept a 10% infection risk for a 10-year remission Conclusion Significant portion of the patients with IBD believe that they are at increased risk of contracting SARS-CoV-2 infection, and more than half of them related the increase risk to their IBD treatment. However, despite their fear most patients felt safe enough to continue their treatment. Patients with more severe disease and treated with biologics experienced higher levels of anxiety, depression and fear of COVID-19 infection. Identifying and addressing these fears early might increase patient’s adherence to treatment and prevent the hazardous effects of discontinuation of treatment.

Background Cannabis is often used by patients with ulcerative colitis, but controlled studies are few. We aimed to assess the effect of cannabis in improving clinical and inflammatory outcomes in ulcerative colitis patients. Methods In a double-blind, randomized, placebo-controlled trial, patients received either cigarettes containing 0.5 g of dried cannabis flowers with80mgTetrahydrocannabinol (THC)or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment. Results The study included 32 patients. Mean age was 30 years, 14 (43%) females. Lichtiger index improved in the cannabis group from 10.9 (IQR 9–14) to5 (IQR 1–7), (p Conclusion Short term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation.(clinicaltrials.gov NCT01040910).

The mechanisms by which the intestinal microbiome affects intestinal inflammation and disease activity in IBD is not clear. Most of the current data on the association between the intestinal microbiome and IBD is focusing on the intestinal microbial taxa and very little is known about the functionality of the microbiome in this condition. Aim: To construct a live bacterial consortium for reduction of intestinal inflammation in IBD based on a high-resolution functional microbial analysis, and its association with anti-inflammatory processes. Methods: Fecal metagenomics samples (n=581) and corresponding fecal calprotectin (FCP) levels from patients with Crohn’s disease and Ulcerative Colitis were downloaded from the NCBI (SRA SRP057027, http://hmpdacc.org, SRA SRP002163 and SRP056641 (BioProject PRJNA275349)). Computational analysis was performed using PRISM (Biomica Ltd, Rehovot Israel), a proprietary metagenomics analysis platform integrating assembly-based and reference-based analyses for functional genomics profiling and utilizing BioCOGS, Biomica’s internal comprehensive catalogue of microbial gene-orthology groups. We compared microbial functions between subjects based on severity of inflammation (FCP250 and FCP >250 vs FCP Validation of the anti-inflammatory activity of BMC322 was performed using a DSS-induced colitis mouse model. Results: Out of the dozens of identified functions, 32 were related to host anti-inflammatory processes, intestinal barrier integrity and colonocyte function. Our functional microbiome investigation has pointed to novel metabolic mechanisms by which specific strains may attenuate mucosal inflammation. Using functional annotations, we infer the biological processes governing microbe-host interactions contributing to reduced inflammation, and identify 16 bacteria of which 4 strains comprise the full array of the identified microbial functions associated with lower disease severity. These strains comprise BMC322- a novel live-bacterial consortium for inflammation reduction in IBD. The anti-inflammatory activity of these strains was validated in in-vitro studies and demonstrated efficacy in preliminary a mouse model of DSS-induced colitis; including shortening period of recovery, disease activity index and fecal lipocalin 2. Conclusion: High-resolution functional genomics profiling of the gut microbiome enables identification of microbial-derived functions relevant to inflammatory disease activity, and microbial strains bearing specific inflammation-reduction activity. These strains have provided the basis for the construction of a 4-strain consortium for intervention in IBD. Preliminary work has validated the anti-inflammatory activity of these strains and their potential as novel therapeutic modality for IBD.

Recent studies have demonstrated differences in the intestinal microbiota between patients with irritable bowel syndrome (IBS) and healthy controls (HC), suggesting a role for the intestinal microbiota in the pathogenesis of IBS. Alterations in the microbiota have also been implicated in the pathogenesis of abdominal bloating, a commonly reported symptom in IBS. We investigated the relationship between the intestinal microbiota, abdominal bloating, and altered bowel patterns in a cohort of patients with IBS and HC. The 16S rRNA gene from fresh fecal samples was amplified and pyrosequenced by using Roche-454 Titanium chemistry. A Core Measurable Microbiome (CMM) was generated for Operational Taxonomic Unit (OTU) detected in >75% of all samples and compositional features of CMM were compared between groups by Linear Discriminant Analysis (LDA). IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera. When subcategorized based on bloating symptoms and bowel characteristics, the same subjects were also well differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTU differences between the subgroups including IBS with and without bloating, and subtypes based on bowel characteristics. The clear LDA differentiation and the significant microbial taxa differences between the groups imply a significant association of the microbiota with bloating symptoms and bowel characteristics in IBS. These changes in the microbiota may serve as a biomarker for IBS and its clinical subtypes and suggest a role for the intestinal microbiota in the pathogenesis of the main symptoms of the disorder.

Irritable bowel syndrome (IBS) is one of the most common diagnoses made by healthcare providers. Yet the majority of patients with IBS are undiagnosed. The study by Sayuk et al. allows insight into the characteristics of different patient groups, e.g., with and without a formal diagnosis of diarrhea predominant IBS (IBS-D). We discuss the questions raised by this study regarding the importance of making a confident diagnosis, conveying it to patients and their implications for clinical practice.

Irritable bowel syndrome (IBS) is the most prevalent and the best studied functional gastrointestinal disorder. The etiology and the pathogenesis of IBS are still not clear; however, recent studies have implicated a role for alterations in the intestinal microbiota (dysbiosis) in the pathophysiology of the disorder. Epidemiological observations have demonstrated that the development of IBS symptoms is often preceded by a disruption of the individual's normal intestinal microbiota, and microbiological studies have demonstrated compositional differences in the intestinal microbiota between patients with IBS patients and healthy controls. In addition, animal studies and a few recent human clinical studies have demonstrated that compositional changes in the intestinal microbiota in IBS are associated with relevant abnormal gastrointestinal and brain-gut axis functions that are often observed in patients with IBS. This article discusses points of interest from the current research on the microbiota-gut-brain interactions in IBS and highlights the relevance of the emerging data to our understanding of the disorder and the clinical implications for patients' care.

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Distance-based analysis is a popular strategy for evaluating the overall association between microbiome diversity and outcome, wherein the phylogenetic distance between individuals’ microbiome profiles is computed and tested for association via permutation. Despite their practical popularity, distance-based approaches suffer from important challenges, especially in selecting the best distance and extending the methods to alternative outcomes, such as survival outcomes. We propose the microbiome regression-based kernel association test (MiRKAT), which directly regresses the outcome on the microbiome profiles via the semi-parametric kernel machine regression framework. MiRKAT allows for easy covariate adjustment and extension to alternative outcomes while non-parametrically modeling the microbiome through a kernel that incorporates phylogenetic distance. It uses a variance-component score statistic to test for the association with analytical p value calculation. The model also allows simultaneous examination of multiple distances, alleviating the problem of choosing the best distance. Our simulations demonstrated that MiRKAT provides correctly controlled type I error and adequate power in detecting overall association. “Optimal” MiRKAT, which considers multiple candidate distances, is robust in that it suffers from little power loss in comparison to when the best distance is used and can achieve tremendous power gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT to real microbiome datasets to show that microbial communities are associated with smoking and with fecal protease levels after confounders are controlled for.

Background: The intestinal microbiota is associated with human health and diseases. The luminal microbiota (LM) and the mucosal-associated microbiota (MAM) are 2 distinct ecosystems with different metabolic and immunological functions. Aim: To characterize the intestinal LM and MAM in humans using high throughput sequencing of the 16S rRNA gene. Methods: Fresh fecal samples and distal colonic mucosal biopsies collected from 24 healthy subjects before (fecal) and during (mucosa) a flexible sigmoidoscopy of an un-prepared bowel. High throughput sequencing of the 16S rRNA gene was used to characterize bacterial communities. Sequences were processed using the QIIME pipeline. Results: LM and MAM populations were significantly different (ANOSIM: R = 0.49, P = 0.001). The LM displayed tighter clustering compared to the MAM (average weighted UniFrac distances 0.27 ± 0.05 vs. 0.43 ± 0.09, P < 0.001, respectively), and showed higher diversity (Shannon diversity index: 4.96 ± 0.37 vs 4.14 ± 0.56, respectively, P < 0.001). The dominant phyla in the LM and MAM were significantly different: Firmicutes (41.4% vs. 29.1%, FDR < 0.0001, respectively), Bacteroidetes (20.2% vs. 26.3%, FDR < 0.05, respectively), Actinobacteria (22% vs. 12.6%, FDR < 0.0001, respectively) and Proteobacteria (9.3% vs. 19.3%, FDR < 0.0001, respectively). The abundance of 56 genera differed significantly (FDR < 0.1) between the 2 niches. All of the genera in the fecal microbiota were present in the MAM while 10 genera were found to be unique to the MAM. Conclusion: The LM and MAM are distinct microbial ecosystems that differ significantly from each other in microbial diversity and composition. These two microbial niches should be investigated independently to better understand the role of the intestinal microbiota in health and disease.

Emerging data from epidemiologic, microbiome, and physiology research in patients with functional bowel disorders (FBDs) provide evidence for a linkage between alterations in the intestinal microbiota and FBDs. However, currently most of the data is based on association studies, and the causality role of the microbiota in these disorders is not established. Growing evidence for compositional changes and the increasing recognition of the association between the intestinal microbiota and gut-brain functions that are relevant to the pathophysiology and/or clinical symptoms of FBDs have led to increased interest in manipulating the intestinal microbiota for the treatment of these disorders.

Laboratory medicine is ripe for a holistic approach to human disease that includes evaluation of human and microbial cells. Advancements in our understanding of the human microbiome are leading to new ideas regarding the diagnosis and management of human diseases. Nucleic acid sequencing, mass spectrometry, and immunoassays will facilitate the application of microbiome science to medical microbiology and clinical chemistry. Biomedical advances in the human microbiome will enlarge the scope of laboratory medicine and result in new diagnostic and disease monitoring strategies. Collaborative efforts within the International Human Microbiome Consortium and specific large-scale research initiatives such as Metagenomics of the Human Intestinal Tract and the Human Microbiome Project have documented differences in microbial composition and function in healthy and diseased states. Diagnostic applications of the microbiome can be divided into two categories: diagnosis of infectious diseases and monitoring of microbial components of noncommunicable chronic diseases. The diagnosis of human infections and selection of antimicrobial agents may be refined in the context of the microbiome. Rather than focusing solely on identification of the etiologic agent(s) of infection, clinical laboratories could evaluate the microbiome at a specific body site of interest. For example, rapid detection of Clostridium difficile in stool specimens in cases of recurrent C. difficile infection may be tested in parallel with stool-based 16S rRNA gene sequencing to evaluate the extent of dysbiosis or cooccurrence of other enteric pathogens. Microbial metabolites may provide useful microbial biomarkers to monitor effective treatment in chronic infections such as recurrent C. difficile associated disease. These parallel evaluations could aid medical decision-making regarding selection of antimicrobial agents or fecal microbiota transplantation (FMT).6 Advances in microbiome discovery are also altering the field of human microbiology for noncommunicable chronic diseases with a microbial component. For example, specific changes in microbial composition and patterns of intestinal dysbiosis …

Background In a recent double-blinded clinical trial the probiotic combination of L-NCFM and B-LBi07 reduced bloating symptoms in patients with functional bowel disorder; an effect more evident in those who reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic MOR and CB2 expression and reduced visceral sensitivity.

Summary Objectives Ginger is one of the most commonly used herbal medicines for irritable bowel syndrome (IBS) but no data exists about its effectiveness. Design Double blind randomized controlled trial. Setting University of North Carolina, Chapel Hill, North Carolina, USA. Intervention Forty-five IBS patients were randomly assigned to three groups: placebo, 1 g of ginger, and 2 g of ginger daily for 28 days. Main outcome measures The IBS severity scale (IBS-SS) was administered, as well as adequate relief of symptoms scale. A responder was defined as having at least 25% reduction in IBS-SS post-treatment. Results There were 57.1% responders to placebo, 46.7% to 1 g and 33.3% to 2 g of ginger. Adequate relief was reported by 53.3% on placebo and 53.3% in both ginger groups combined. Side effects were mild and reported by 35.7% in the placebo and 16.7% in the ginger groups. Conclusions This double blind randomized controlled pilot study suggests ginger is well tolerated but did not perform better than placebo. Larger trials are needed before any definitive conclusions can be drawn.

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.

Bifidobacterium infantis 35624 is a probiotic that is used often in patients with irritable bowel syndrome (IBS). Non-patients with bowel symptoms may differ from patients with IBS in the impact of their bowel symptoms on illness severity, healthcare and treatment seeking behavior. The aim of this study is to assess the efficacy of B. infantis 35624 (10A double-blind, randomized, placebo-controlled, parallel study with a 2-week placebo run-in phase followed by a 4-week intervention phase was conducted at ten clinical centers (USA). Subjects were recruited from the general population by advertisement. The study randomized 302 subjects who experienced abdominal discomfort and bloating ≥2-times per week for at least three months but have not seen a physician or received prescribed medication for their symptoms in the past 12 months. Subjects were assessed for pre- to post-intervention changes in symptom severity (on a 6-point Likert scale; 0=none, 5=very severe) and frequency (symptoms-free days).A total of 275 subjects (mean age 42 years, 79% female, 74% Caucasian) provided evaluable data. Overall mean severity scores at baseline were 2.4 for abdominal discomfort and 2.5 for bloating with no significant differences between the placebo and probiotic groups. Both groups showed significant (P0.05) improvement in abdominal discomfort and bloating scores over the 4-week intervention period. Mean severity symptom scores at the end of intervention showed no significant differences between the probiotic and the placebo groups in either abdominal discomfort or bloating (P0.3). The frequency of abdominal bloating-free days was greater in the B. infantis 35624 group compared to the placebo group (P0.05). Both regimens were well tolerated.Unlike previous clinical studies in patients with IBS, B. infantis 35624 did not show a significant improvement in the mean severity of symptoms of abdominal discomfort and bloating in a non-patient population. This may be explained by the high placebo effect and the lower impact of functional bowel symptoms in the non-patient population.

Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.

BACKGROUND Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. GOALS To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. STUDY This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. RESULTS A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P

The colonization pattern of intestinal microbiota during childhood may impact health later in life, but children older than 1 year are poorly studied. We followed healthy children aged 1-4 years (n=28) for up to 12 months, during which a synbiotic intervention and occasional antibiotics intake occurred, and compared them with adults from the same region. Microbiota was quantified with the HITChip phylogenetic microarray and analyzed with linear mixed effects model and other statistical approaches. Synbiotic administration increased the stability of Actinobacteria and antibiotics decreased Clostridium cluster XIVa abundance. Bacterial diversity did not increase in 1- to 5-year-old children and remained significantly lower than in adults. Actinobacteria, Bacilli and Clostridium cluster IV retained child-like abundances, whereas some other groups were converting to adult-like profiles. Microbiota stability increased, with Bacteroidetes being the main contributor. The common core of microbiota in children increased with age from 18 to 25 highly abundant genus-level taxa, including several butyrate-producing organisms, and developed toward an adult-like composition. In conclusion, intestinal microbiota is not established before 5 years of age and diversity, core microbiota and different taxa are still developing toward adult-type configuration. Discordant development patterns of bacterial phyla may reflect physiological development steps in children.

Accumulating data have strongly linked gut microbes to human health. Accordingly, manipulating intestinal microbiota holds promise as a potential treatment for restoring health. Although antibiotics have been the primary clinical choice for achieving this objective, supplementing the gastrointestinal microbiota with probiotics—or encouraging their growth with prebiotics—is now widely used as an alternative approach. Among gastrointestinal disorders, data of varying quality support the use of probiotics in preventing and treating diarrhea, inflammatory bowel disease (particularly pouchitis), irritable bowel syndrome, and liver disease. Although some data are indeed promising, the profusion of probiotic products and the fact that species, strain, and formulation all clearly influence efficacy have led to significant confusion regarding the best choice for different indications. Although sufficient evidence is not currently available to provide a clear guidance on the best probiotic for a particular clinical indication, key scientific concepts are now emerging. Building on these concepts, this review will provide practical information on the use of these products in clinical practice.

Background/Aims Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system. Methods Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera. Results Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa. Conclusions Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies.

The pathophysiology of irritable bowel syndrome (IBS) is still unknown. However, several lines of epidemiological, physiological, and clinical data suggest a role for intestinal bacteria in the pathogenesis of the disorder. Recent microbiology studies demonstrated differences in the composition of the intestinal microbiota between patients with IBS and healthy individuals. In addition, physiological studies have shown that manipulation of the intestinal microbiota by antibiotics, prebiotics, or probiotics can affect intestinal functions (eg, motility and sensation) relevant in the pathogenesis of IBS. Several randomized control trials comparing the effects of probiotics versus placebo in IBS have been published. Despite considerable differences in study design, dosing regimens, probiotic species used, and reported clinical end points, the current data indicate improving IBS symptoms and reducing the risk of persistent IBS symptoms. The data on the use of probiotics in children with IBS is more limited but is also suggestive for beneficial effects. The inconsistencies between the studies underline the need to look at each probiotic product separately for specific conditions, symptoms, and patient populations. This review article discusses the rationale for targeting the intestinal microbiota in patient with IBS and provides an overview and a critical evaluation of the currently available clinical data on the use of probiotics in the treatment of patients with IBS.

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS ( n = 16) and healthy controls ( n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls ( P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated.

In November 2008, a group of scientists met at the 6th Meeting of the International Scientific Association of Probiotics and Prebiotics (ISAPP) in London, Ontario, Canada, to discuss the functionality of prebiotics. As a result of this, it was concluded that the prebiotic field is currently dominated by gastrointestinal events. However, in the future, it may be the case that other mixed microbial ecosystems may be modulated by a prebiotic approach, such as the oral cavity, skin and the urogenital tract. Therefore, a decision was taken to build upon the current prebiotic status and define a niche for ‘dietary prebiotics’. This review is co-authored by the working group of ISAPP scientists and sets the background for defining a dietary prebiotic as ‘‘a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health’’.

Functional gastrointestinal disorders (FGIDs) are highly prevalent in Western countries yet no single mechanism or etiological agent that initiates IBS has been identified. Current research has implicated the intestinal microbiota with FGIDs. This article reviews the available literature/data regarding the intestinal microbiota and FGIDS. The possible relationships between the intestinal microbiota and the intestinal function and functional bowel symptoms are discussed.

This study was designed to determine whether biofeedback is more effective than diazepam or placebo in a randomized, controlled trial for patients with pelvic floor dyssynergia-type constipation, and whether instrumented biofeedback is necessary for successful training. A total of 117 patients participated in a four-week run-in (education and medical management). The 84 who remained constipated were randomized to biofeedback (n=30), diazepam (n=30), or placebo (n=24). All patients were trained to do pelvic floor muscle exercises to correct pelvic floor dyssynergia during six biweekly one-hour sessions, but only biofeedback patients received electromyography feedback. All other patients received pills one to two hours before attempting defecation. Diary data on cathartic use, straining, incomplete bowel movements, Bristol stool scores, and compliance with homework were reviewed biweekly. Before treatment, the groups did not differ on demographic (average age, 50 years; 85 percent females), physiologic or psychologic characteristics, severity of constipation, or expectation of benefit. Biofeedback was superior to diazepam by intention-to-treat analysis (70 vs. 23 percent reported adequate relief of constipation 3 months after treatment, chi-squared=13.1, P

Clostridium difficile is an anaerobic, gram positive, sporulating, toxin-producing bacillus which causes a spectrum of clinical disease ranging from an asymptomatic carrier state to toxic megacolon and fulminant disease. Infection with C. difficile is an expensive and pervasive health care burden. The current theory regarding the development of C. difficile infection (CDI) suggests that disruption of the structure and/or function of an individual's normal intestinal microbiota enables colonization by C. difficile, and in the absence of an effective immune response, the bacteria causes illness. In this article we discuss the role of the colonic microbiota in the development of CDI and the potential role of probiotics in preventing and treating CDI. We review the evidence from in vitro laboratory and pre-clinical studies, as well as evidence from clinical studies and discuss the current recommendations for the use of probiotics for CDI in clinical practice.

Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes.IBS patients who satisfied the Rome III criteria (114) and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: intestinal intraluminal pH and fecal short-chain fatty acids (SCFAs). Intraluminal pH and intestinal transit times were measured in the small and large bowel using a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal SCFAs including acetate, propionate, butyrate, and lactate were analyzed by capillary gas chromatography in all enrolled subjects. Correlations between intestinal pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were analyzed.Colonic intraluminal pH levels were significantly lower in IBS patients compared with HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC, P=0.042). There were no differences in total and segmental pH levels in the small bowel between IBS patients and HC (6.8 vs. 6.8, P=not significant). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFA level was significantly lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The total SCFA level in all IBS subjects was similar with that of HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT and positively with stool frequency.Colonic intraluminal pH is decreased, suggesting higher colonic fermentation, in IBS patients compared with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial fermentation.

This paper describes the consensus opinion of the participants in the 4th Triennial Yale/Harvard Workshop on Probiotic Recommendations. The recommendations update those of the first 3 meetings that were published in 2006, 2008, and 2011. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome and Clostridium difficile diarrhea are reviewed. In addition, we have added recommendations for liver disease for the first time. As in previous publications, the recommendations are given as A, B, or C ratings.