Microbial and Dietary Factors in the Pathogenesis of Chronic, Immune-Mediated Intestinal Inflammation

2006 ◽  
pp. 35-54 ◽  
Author(s):  
R. Balfour Sartor
Keyword(s):  
Intestinal Inflammation ◽  
Dietary Factors ◽  
Immune Mediated

Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice

2009 ◽  
Vol 296 (3) ◽  
pp. G685-G695 ◽  
Author(s):  
Stephan C. Bischoff ◽  
Reiner Mailer ◽  
Oliver Pabst ◽  
Gisela Weier ◽  
Wanda Sedlik ◽  
...  
Keyword(s):  
Serotonin Reuptake ◽  
Sulfonic Acid ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Colonic Motility ◽  
Trinitrobenzene Sulfonic Acid ◽  
Targeted Deletion ◽  
Immune Mediated ◽  
Serotonin Reuptake Transporter

Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system. Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.

scholarly journals The Adenosine System at the Crossroads of Intestinal Inflammation and Neoplasia

2020 ◽  
Vol 21 (14) ◽  
pp. 5089
Author(s):  
Vanessa D’Antongiovanni ◽  
Matteo Fornai ◽  
Carolina Pellegrini ◽  
Laura Benvenuti ◽  
Corrado Blandizzi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Receptor Subtype ◽  
Colorectal Tumorigenesis ◽  
Adverse Conditions ◽  
Immune Mediated ◽  
A1 Receptor ◽  
G Protein Coupled ◽  
Critical Overview

Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A1 receptor subtype (A1), A2A, A2B, and A3. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage. However, a prolonged persistence of increased adenosine concentrations can be deleterious, participating in the creation of an immunosuppressed niche, ideal for neoplasia onset and development. Based on this evidence, the present review has been conceived to provide a comprehensive and critical overview of the involvement of adenosine system in shaping the molecular mechanisms underlying the enteric chronic inflammation and in promoting the generation of an immunosuppressive niche useful for the colorectal tumorigenesis.

scholarly journals Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation

2013 ◽  
Vol 305 (8) ◽  
pp. G573-G584 ◽  
Author(s):  
Bo Liu ◽  
Ajay S. Gulati ◽  
Viviana Cantillana ◽  
Stanley C. Henry ◽  
Elyse A. Schmidt ◽  
...  
Keyword(s):  
Sodium Sulfate ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Paneth Cell ◽  
Dextran Sodium Sulfate ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Clinical Responses ◽  
Granule Morphology ◽  
Intracellular Infections

Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase ( IRG) M ( IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

CREAM study: Clinical correlation between immunotherapy-RElated clinical outcome and intestinal microbiote in metastatic patients.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS215-TPS215
Author(s):  
Laura Orgiano ◽  
Alessio Cubeddu ◽  
Silvia Camera ◽  
Roberta Mascia ◽  
Mariele Dessi ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Intestinal Inflammation ◽  
Bacterial Species ◽  
Intestinal Flora ◽  
Gastrointestinal Diseases ◽  
Intestinal Microbes ◽  
Physiological Tolerance ◽  
Immune Mediated ◽  
Single Center Study ◽  
Innovative Therapies

TPS215 Background: It's known that composition of intestinal flora can influence the development of inflammatory gastrointestinal diseases, even though the association of inflammation with specific intestinal microbes is still unknown, because the inflammation and its treatment can change the composition of microbiote. Some bacterial species are essential to maintain the mucosal physiological tolerance, although species such as Bacteroides, Clostridium and Faecalibacterium can induce the up-regulation of T-cells and stimulate the production of anti-inflammatory cytokines. Innovative therapies such as anti-CTLA-4 antibody and inhibitors of the PD-1 receptor are particularly involved in the up-regulation of lymphocyte system: among their side effects, the most relevant are those immune-mediated such as hypophysitis, thyroiditis and colitis. In particular this last one usually occurs within 16weeks from the start of treatment: about one third of patients develop intestinal inflammation of any grade as a result of immune system dysregulation. So, the high incidence of colitis in patients treated with immunotherapy offers the possibility to characterize the intestinal microbiote before the development of immune-mediated inflammation. In addition, our curiosity has been oriented to the response to immunotherapy and the HLA class expressed by our patients: which any better predictor of response to immunological treatment than this one? Methods: Our is a single-center study of clinical and biological parameters prospectively stratified. Specifically, we collect from patients eligible for immunotherapy a blood sample to analyze HLA class and an other one to analyze serum cytokines levels, inflammatory indices and a sample of fecal material at baseline and at least after 3 administrations of treatment: actually we enrolled 34 out of 40 planned patients; we suppose to complete the enrollment in 2 months. According to preliminary data published in literature, we expect to find an alteration of intestinal microbiote in metastatic patients treated with immunotherapy. Once we'll identify it, we want to assess whether there is any correlation with the patient's clinical outcome.

scholarly journals The Resolution of Intestinal Inflammation: The Peace-Keeper’s Perspective

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 344 ◽  
Author(s):  
Onali ◽  
Favale ◽  
Fantini
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Inflammation ◽  
Regulatory Mechanisms ◽  
Inflammatory Factors ◽  
Active Process ◽  
Resolution Of Inflammation ◽  
Immune Mediated ◽  
Inflammatory Bowel ◽  
Loss Of Tolerance ◽  
Pathogenic Process

The uncontrolled activation of the immune system toward antigens contained in the gut lumen in genetically predisposed subjects is believed to be the leading cause of inflammatory bowel disease (IBD). Two not mutually exclusive hypotheses can explain the pathogenic process leading to IBD. The first and mostly explored hypothesis states that the loss of tolerance toward gut microbiota antigens generates an aberrant inflammatory response that is perpetuated by continuous and unavoidable exposure to the triggering antigens. However, the discovery that the resolution of inflammation is not the mere consequence of clearing inflammatory triggers and diluting pro-inflammatory factors, but rather an active process in which molecular and cellular elements are involved, implies that a defect in the pro-resolving mechanisms might cause chronic inflammation in different immune-mediated diseases, including IBD. Here we review data on pro-resolving and counter-regulatory mechanisms involved in the resolution of inflammation, aiming to identify their possible involvement in the pathogenesis of IBD.

scholarly journals Dietary Factors as Triggers of Low-Grade Chronic Intestinal Inflammation in Poultry

2020 ◽  
Vol 8 (1) ◽  
pp. 139 ◽  
Author(s):  
Gabriela Cardoso Dal Pont ◽  
Morgan Farnell ◽  
Yuhua Farnell ◽  
Michael H. Kogut
Keyword(s):  
Inflammatory Response ◽  
Intestinal Inflammation ◽  
Dietary Factors ◽  
Low Grade ◽  
Poultry Production ◽  
Soluble Fiber ◽  
Subsequent Loss ◽  
Dietary Components ◽  
Nutritional Compounds ◽  
Chronic Intestinal Inflammation

Inflammation is the reaction of the immune system to an injury; it is aimed at the recovery and repair of damaged tissue. The inflammatory response can be beneficial to the animal since it will reestablish tissue homeostasis if well regulated. However, if it is not controlled, inflammation might lead to a chronic response with a subsequent loss of tissue function. The intestine is constantly exposed to a number of environmental triggers that stimulate inflammation and lead to a reduction in performance. The diet and dietary components constitute consistent inflammatory triggers in poultry. Dietary components, such as anti-nutritional compounds, oxidized lipids, mycotoxins, and excess of soluble fiber or protein, are all capable of inducing a low-grade inflammatory response in the intestine of broilers throughout a 5-week grow-out period. We hypothesized that dietary factor-induced chronic intestinal inflammation is a key driver of the lower performance and higher incidence of intestinal problems observed in poultry production. Therefore, this review was aimed at exploring feed-induced chronic inflammation in poultry, the constituents of the diet that might act as inflammatory triggers and the possible effects of chronic intestinal inflammation on the poultry industry.

scholarly journals Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322670
Author(s):  
Laura A Bolte ◽  
Arnau Vich Vila ◽  
Floris Imhann ◽  
Valerie Collij ◽  
Ranko Gacesa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dietary Patterns ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Meta Analysis ◽  
Dietary Factors ◽  
Metagenomic Sequencing ◽  
Microbial Composition ◽  
Anti Inflammatory

ObjectiveThe microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. We aim to unravel interactions between diet, gut microbiota and their functional ability to induce intestinal inflammation.DesignWe investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population. Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Associations between diet and microbial features were explored per cohort, followed by a meta-analysis and heterogeneity estimation.ResultsWe identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (false discovery rate<0.05). Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways. The opposite was found for plant foods and fish, which were positively associated with short-chain fatty acid-producing commensals and pathways of nutrient metabolism.ConclusionWe identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.

scholarly journals Dietary Composition and Effects in Inflammatory Bowel Disease

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1398 ◽  
Author(s):  
Fernando Castro ◽  
Heitor S. P. de Souza
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Dietary Habits ◽  
Intestinal Inflammation ◽  
Dietary Factors ◽  
Food Components ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.

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