A229 PROMOTION OF COLONIC ANASTOMOTIC HEALING WITH PERIOPERATIVE SUPPLEMENTATION WITH OLIGOSACCHARIDES

Abstract Background Colorectal resection is a standard procedure in the management of colorectal cancer (CRC) and inflammatory bowel disease. Anastomotic leak (AL) is a major complication in colorectal resections, and the gut microbiota may play a role in the healing and development of AL. Short-chain fatty acids (SCFAs), namely butyrate, have been involved in anastomotic healing when administered into the bowel via enema. Due to the mechanical stress associated with enemas after the confection of a fresh and fragile anastomosis, other butyrate-increasing strategies are required. Aims To promote anastomotic healing and prevent AL by using inulin and galacto-oligosaccharides (GOS) supplementation to modulate the microbiota toward a butyrate-producing profile. Methods Mice were fed diets supplemented with inulin, GOS or cellulose, as a non-fermentable control, for two weeks and underwent a proximal colonic anastomosis under general anesthesia. Healing of the anastomosis, both macroscopically and microscopically, was assessed six days after surgery. Epithelial proliferation, mucus production and integrity of the gut barrier were assessed. Results Inulin and GOS supplementation increased SCFAs in the colon and were associated with better postoperative weight recovery and macroscopic anastomotic healing. Microscopically, mucosal continuity was promoted by inulin and GOS. Mucus production was found to be similar in all groups. The gut barrier was found to be improved with inulin and GOS as shown by less bacterial translocation. Conclusions Inulin and GOS may prevent AL and promote anastomotic healing. This effect appears to be mediated by improved mucosal proliferation. Funding Agencies CIHRNatural Sciences and Engineering Research Council of Canada; Institut du cancer de Montréal; Fonds de recherche du Québec en santé

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A200 VEDOLIZUMAB IS AN EFFECTIVE TREATMENT OPTION FOR NON INFLAMMATORY BOWEL DISEASE RELATED ENTEROPATHY

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.198 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 224-225

Author(s):

H Akhtar ◽

T Nguyen ◽

V Jairath

Keyword(s):

Clinical Response ◽

Case Series ◽

Duration Of Treatment ◽

Effective Treatment Option ◽

Histologic Response ◽

Funding Agencies ◽

Full Text Review ◽

Language Restriction ◽

Inflammatory Bowel ◽

Cell Adhesion Molecule 1

Abstract Background Vedolizumab is an α4β7 integrin antagonist which inhibits intestinal T-cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. Its gut selective mode of action and safety profile have lead to reports of off-label use of vedolizumab for non-IBD related inflammatory intestinal disorders. Aims We conducted a literature review to assess clinical, endoscopic and histologic improvement in patients treated with Vedolizumab for non-IBD enteropathies refractory to conventional therapy. Methods EMBASE, Medline, Clinicaltrials.gov and Cochrane CENTRAL were searched on September 12, 2019 for case studies, case series and cohort studies without language restriction yielding 356 studies with 164 duplicates, 74 non-applicable studies, leaving 118 studies. After full text review, 98 studies were excluded, leaving 20 included studies. Results 65% of patients (51/79) achieved clinical response. 40.5% (15/37) of patients experienced endoscopic improvement and 33% (17/51) of patients experienced histologic improvement. The duration of treatment varied from patients receiving only induction doses to up to 70 months for maintenance therapy. There were four reported cases of withdrawal due to adverse events from Vedolizumab. Conclusions In a treatment refractory population, over 60% of patients reported to have a clinical response and one-third endoscopic/histologic response, indicating that Vedolizumab is a viable option for patients with refractory non-IBD enteropathy. Funding Agencies None

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Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

Gastroenterology Insights ◽

10.3390/gastroent12010006 ◽

2021 ◽

Vol 12 (1) ◽

pp. 56-66

Author(s):

Toumi Ryma ◽

Arezki Samer ◽

Imene Soufli ◽

Hayet Rafa ◽

Chafia Touil-Boukoffa

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Symptoms ◽

Therapeutic Potential ◽

Short Chain Fatty Acids ◽

Active Metabolites ◽

Complex Disorders ◽

Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

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Effects of Anti-Cytokine Antibodies on Gut Barrier Function

Mediators of Inflammation ◽

10.1155/2019/7028253 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Fang Liu ◽

Seul A. Lee ◽

Stephen M. Riordan ◽

Li Zhang ◽

Lixin Zhu

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Barrier Function ◽

Inflammatory Diseases ◽

Immunomodulatory Effects ◽

Gut Barrier ◽

Barrier Integrity ◽

Chronic Inflammatory Diseases ◽

Gut Barrier Function ◽

Inflammatory Bowel

Anti-cytokine antibodies are used in treating chronic inflammatory diseases and autoimmune diseases such as inflammatory bowel disease and rheumatic diseases. Patients with these diseases often have a compromised gut barrier function, suggesting that anti-cytokine antibodies may contribute to the re-establishment of gut barrier integrity, in addition to their immunomodulatory effects. This paper reviews the effects of anti-cytokine antibodies on gut barrier function and their mechanisms.

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Inflammatory Bowel Diseases: Host-Microbial-Environmental Interactions in Dysbiosis

Diseases ◽

10.3390/diseases8020013 ◽

2020 ◽

Vol 8 (2) ◽

pp. 13

Author(s):

Catherine Colquhoun ◽

Michelle Duncan ◽

George Grant

Keyword(s):

Inflammatory Bowel Diseases ◽

Early Life ◽

Secretory Iga ◽

Mucus Production ◽

Functional Changes ◽

Environmental Interactions ◽

Intestinal Dysbiosis ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Abundance And Diversity

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are world-wide health problems in which intestinal dysbiosis or adverse functional changes in the microbiome are causative or exacerbating factors. The reduced abundance and diversity of the microbiome may be a result of a lack of exposure to vital commensal microbes or overexposure to competitive pathobionts during early life. Alternatively, many commensal bacteria may not find a suitable intestinal niche or fail to proliferate or function in a protective/competitive manner if they do colonize. Bacteria express a range of factors, such as fimbriae, flagella, and secretory compounds that enable them to attach to the gut, modulate metabolism, and outcompete other species. However, the host also releases factors, such as secretory IgA, antimicrobial factors, hormones, and mucins, which can prevent or regulate bacterial interactions with the gut or disable the bacterium. The delicate balance between these competing host and bacteria factors dictates whether a bacterium can colonize, proliferate or function in the intestine. Impaired functioning of NOD2 in Paneth cells and disrupted colonic mucus production are exacerbating features of CD and UC, respectively, that contribute to dysbiosis. This review evaluates the roles of these and other the host, bacterial and environmental factors in inflammatory bowel diseases.

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In Vitro Characterization of Gut Microbiota-Derived Commensal Strains: Selection of Parabacteroides distasonis Strains Alleviating TNBS-Induced Colitis in Mice

Cells ◽

10.3390/cells9092104 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2104 ◽

Cited By ~ 1

Author(s):

Bernardo Cuffaro ◽

Aka L. W. Assohoun ◽

Denise Boutillier ◽

Lenka Súkeníková ◽

Jérémy Desramaut ◽

...

Keyword(s):

Gut Microbiota ◽

Chronic Diseases ◽

Protective Effects ◽

Gut Barrier ◽

Regulatory T Lymphocytes ◽

In Vitro Characterization ◽

Health Promoting ◽

Inflammatory Bowel

Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.

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Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

Frontiers in Nutrition ◽

10.3389/fnut.2021.718356 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giovanni Barbara ◽

Maria Raffaella Barbaro ◽

Daniele Fuschi ◽

Marta Palombo ◽

Francesca Falangone ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Cell Damage ◽

Short Chain Fatty Acids ◽

The Body ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Inflammatory Bowel ◽

Irritable Bowel

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

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Combined Staged Surgery and Negative-Pressure Wound Therapy for Closure of a Giant Omphalocele

Case Reports in Pediatrics ◽

10.1155/2021/5234862 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Vlad Laurentiu David ◽

Mihai Cristian Neagu ◽

Aurelia Sosoi ◽

Maria Corina Stanciulescu ◽

Florin George Horhat ◽

...

Keyword(s):

Negative Pressure ◽

Negative Pressure Wound Therapy ◽

Standard Procedure ◽

Surgical Techniques ◽

Major Complication ◽

Prosthetic Material ◽

Pressure Therapy ◽

Surgical Closure ◽

Giant Omphalocele ◽

Point Of Interest

The management of giant omphaloceles had always been a point of interest for the pediatric surgeons. Many surgical techniques were proposed, but none of them succeeded to become the standard procedure in closing the congenital abdominal defect. We present a case of giant omphalocele in which we used staged surgical closure combined with a prosthetic patch, with negative-pressure therapy and, finally, definitive surgical closure. Even though a major complication occurred during the treatment, we were able to close the defect without any prosthetic material left in place.

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Mucin-mimetic action of capsaicin improves high fat diet-induced gut barrier dysfunction in mice colon

10.1101/2021.08.04.455153 ◽

2021 ◽

Author(s):

Vijay Kumar ◽

Vibhu Kumar ◽

Neha Mahajan ◽

Jasleen Kaur ◽

Kirti Devi ◽

...

Keyword(s):

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Barrier Dysfunction ◽

Gut Barrier ◽

Mucus Production ◽

Diet Induced Obesity ◽

Transient Receptor ◽

Junction Proteins

The gut barrier, including tight junction proteins and mucus layers, is the first line of defense against physical, chemical, or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While its mode of action is well established to enhance energy expenditure, metabolism and prevent dysbiosis, the more local effects on the host gut, particularly the gut barrier and mucus system remain elusive. We employed a diet-induced obesity model to investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena. Mucin feeding reflected most of the effects produced by capsaicin, indicating that mucus modulation by capsaicin plays a crucial role in its anti-obesity effects. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment.

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Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?

F1000Research ◽

10.12688/f1000research.6456.1 ◽

2015 ◽

Vol 4 ◽

pp. 1146 ◽

Cited By ~ 2

Author(s):

Jonathan D. Kaunitz ◽

Piyush Nayyar

Keyword(s):

Fatty Acids ◽

Short Chain Fatty Acids ◽

Intestinal Microbiome ◽

Mucosal Barrier ◽

Neural Systems ◽

Integrative Approach ◽

Mucosal Barrier Function ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Glucagon Like Peptide

The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn’s disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules. In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis. Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.

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Colon Innervating TRPA1 Positive Nociceptors Influence Mucosal Health In Mice

10.1101/2021.10.17.464752 ◽

2021 ◽

Author(s):

Mahendra Bishnoi ◽

Vibhu Kumar ◽

Vijay Kumar ◽

Kirti Devi ◽

Ajay Kumar ◽

...

Keyword(s):

Transient Receptor Potential ◽

Therapeutic Option ◽

Receptor Potential ◽

Short Chain Fatty Acids ◽

Rectal Administration ◽

Gut Health ◽

Gut Permeability ◽

Mucus Production ◽

Mucosal Lining ◽

Transient Receptor

Introduction: Transient receptor potential ankyrin-1 positive (TRPA1+ve) nociceptors, primarily present as peptidergic neuronal afferents in the colon are sensors of disturbance in lower gastrointestinal tract including pain induced by different pathologies. Their therapeutic role in the alleviation of chronic pain (receptor antagonism and receptor desensitization) associated with inflammatory bowel diseases (IBD) is reported. However, there is limited literature available about their role in formation and sustenance of the mucosal layer, and its interaction with host physiology as well as luminal microbial community. The aim of this study focuses on the effects of nociceptive TRPA1 channel desensitization on colonic mucus production and gut health. Methods: TRPA1+ve nociceptors were desensitized by rectal administration of capsazepine. Ileum, colon was harvested and cecum content was collected. We performed morphological/histological analysis, gut permeability alteration, gene expression changes, colon metabolite profiling, and gut microbial abundance in these animals. Results: We found that presence of TRPA1-positive nociceptors is required for mucus layer integrity, using an intra-rectal capsazepine-induced TRPA1 desensitization model. Desensitization of TRPA1 positive nociceptors resulted in damaged mucosal lining, resultant increase in gut permeability and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. Conclusion: These results suggest that caution may need to be exercised before employing TRPA1 desensitization as a therapeutic option to alleviate pain caused due to IBD.

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