scholarly journals How the Intricate Interaction among Toll-Like Receptors, Microbiota, and Intestinal Immunity Can Influence Gastrointestinal Pathology

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Simona Frosali ◽  
Danilo Pagliari ◽  
Giovanni Gambassi ◽  
Raffaele Landolfi ◽  
Franco Pandolfi ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Inflammatory Diseases ◽  
Intestinal Flora ◽  
Intestinal Immunity ◽  
Toll Like Receptors ◽  
Healthy Human ◽  
Gastrointestinal Pathology ◽  
Food Antigens ◽  
Bowel Diseases ◽  
Inflammatory Processes

The gut is able to maintain tolerance to microbial and food antigens. The intestine minimizes the number of harmful bacteria by shaping the microbiota through a symbiotic relationship. In healthy human intestine, a constant homeostasis is maintained by the perfect regulation of microbial load and the immune response generated against it. Failure of this balance may result in various pathological conditions. Innate immune sensors, such as Toll-like receptors (TLRs), may be considered an interface among intestinal epithelial barrier, microbiota, and immune system. TLRs pathway, activated by pathogens, is involved in the pathogenesis of several infectious and inflammatory diseases. The alteration of the homeostasis between physiologic and pathogenic bacteria of intestinal flora causes a condition called dysbiosis. The breakdown of homeostasis by dysbiosis may increase susceptibility to inflammatory bowel diseases. It is evident that environment, genetics, and host immunity form a highly interactive regulatory triad that controls TLR function. Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes, such as in IBD, colitis, and colorectal cancer. The study of interactions between different components of the immune systems and intestinal microbiota will open new horizons in the knowledge of gut inflammation.

scholarly journals Review Article. Absent in melanoma 2 (AIM2) in the intestine: diverging actions with converging consequences

Inflammasome ◽  
2017 ◽  
Vol 3 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Wiebe Vanhove ◽  
Paul M. Peeters ◽  
Isabelle Cleynen ◽  
Gert Van Assche ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Intestinal Homeostasis ◽  
Caspase 1 ◽  
Essential Components ◽  
Food Antigens ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns

AbstractThe intestinal mucosa is a difficult environment to maintain homeostasis as it is constantly challenged by microbial and food antigens. Maintaining an intact epithelial barrier, a continuous turnover of intestinal epithelial cells and normobiosis of the gut microbiota are essential components to prevent intestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Inflammasomes are critical immune regulators that are involved in all of these processes. They are multiprotein complexes able to assemble upon interaction with a noxious stimulus that will subsequently lead to caspase-1 activation. Activated caspase-1 will orchestrate the maturation and release of proinflammatory cytokines IL-1β and IL-18, and induce pyroptosis, an inflammatory form of cell death. Both cytokine release and pyroptosis are initiated after detection of molecular patterns by a distinct inflammasome sensor protein. Absent in melanoma 2 (AIM2) is such an inflammasome sensor that specifically responds to the presence of double stranded DNA (dsDNA) in the cytoplasm, leading to the recruitment and activation of caspase-1. Recent studies revealed additional roles of AIM2 in controlling epithelial cell proliferation, tight junction expression and the microbiome. Therefore, AIM2 plays a significant role in maintaining intestinal homeostasis. This review focuses on the multifunctional role of AIM2 in intestinal homeostasis by regulating intestinal immunity and preventing colorectal cancer development.

scholarly journals Neuroimmune Interactions in the Gut and Their Significance for Intestinal Immunity

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 670 ◽  
Author(s):  
David J. Brinkman ◽  
Anne S. ten Hove ◽  
Margriet J. Vervoordeldonk ◽  
Misha D. Luyer ◽  
Wouter J. de Jonge
Keyword(s):  
Clinical Trials ◽  
Nervous System ◽  
Immune System ◽  
Current Knowledge ◽  
Unmet Need ◽  
Autonomic Nerves ◽  
Intestinal Immunity ◽  
Intestinal Immune System ◽  
Bowel Diseases ◽  
Inflammatory Processes

Inflammatory bowel diseases (IBD) have a complex, multifactorial pathophysiology with an unmet need for effective treatment. This calls for novel strategies to improve disease outcome and quality of life for patients. Increasing evidence suggests that autonomic nerves and neurotransmitters, as well as neuropeptides, modulate the intestinal immune system, and thereby regulate the intestinal inflammatory processes. Although the autonomic nervous system is classically divided in a sympathetic and parasympathetic branch, both play a pivotal role in the crosstalk with the immune system, with the enteric nervous system acting as a potential interface. Pilot clinical trials that employ vagus nerve stimulation to reduce inflammation are met with promising results. In this paper, we review current knowledge on the innervation of the gut, the potential of cholinergic and adrenergic systems to modulate intestinal immunity, and comment on ongoing developments in clinical trials.

scholarly journals IBD considerations in spondyloarthritis

2020 ◽  
Vol 12 ◽  
pp. 1759720X2093941
Author(s):  
Caroline Di Jiang ◽  
Tim Raine
Keyword(s):  
Inflammatory Diseases ◽  
Drug Dosing ◽  
Inflammatory Conditions ◽  
Gastrointestinal Pathology ◽  
Immune Mediated ◽  
Form Part ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Gastrointestinal Inflammation ◽  
The Difference

Spondyloarthritis (SpA) may be regarded a family of auto-inflammatory conditions with inflammation focused on the joints. These form part of a wider family of immune-mediated inflammatory diseases, which include inflammatory bowel diseases (IBD). These conditions share common elements of pathophysiology and it is perhaps unsurprising, therefore, that individuals with SpA frequently manifest gastrointestinal inflammation, to which the physician managing the patient with SpA must be alert. In this article, we review the shared epidemiology and pathophysiology of these conditions, before discussing approaches to diagnosis and management of inflammatory gastrointestinal pathology in patients seen in rheumatology clinics. In particular, we discuss the difference between non-specific gastrointestinal inflammation commonly described in this patient group and the more specific diagnosis of Crohn’s disease or ulcerative colitis. We describe the appropriate diagnostic workup for patients suspected of having IBD. In addition, we discuss how a diagnosis of IBD can inform treatment selection, highlighting important differences in treatment choice, drug dosing, monitoring and drug safety for this particular comorbid patient population.

The role of macrophages in inflammatory bowel diseases

2009 ◽  
Vol 11 ◽  
Author(s):  
Sigrid E.M. Heinsbroek ◽  
Siamon Gordon
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Responses ◽  
Intestinal Flora ◽  
The Body ◽  
Intestinal Immunity ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Intestinal Macrophage ◽  
Small And Large Intestine

The small and large intestine contain the largest number of macrophages in the body and these cells are strategically located directly underneath the epithelial layer, enabling them to sample the lumen. Such intestinal macrophages have a different phenotype from other tissue macrophages in that they ingest and may kill microbes but they do not mediate strong pro-inflammatory responses upon microbial recognition. These properties are essential for maintaining a healthy intestine. It is generally accepted that tolerance to the intestinal flora is lost in inflammatory bowel diseases, and genes involved in microbial recognition, killing and macrophage activation have already been associated with these diseases. In this review, we shed light on the intestinal macrophage and how it influences intestinal immunity.

scholarly journals Sini Decoction Ameliorates Colorectal Cancer and Modulates the Composition of Gut Microbiota in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yishan Wang ◽  
Xiaodi Zhang ◽  
Jiawei Li ◽  
Ying Zhang ◽  
Yingjie Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pathogenic Bacteria ◽  
Bacillus Coagulans ◽  
Mucosal Barrier ◽  
Intestinal Immunity ◽  
Mice Model ◽  
Tumor Number ◽  
Bowel Diseases ◽  
Mucosal Layer ◽  
Mucin 2

Sini Decoction (SND), as a classic prescription of Traditional Chinese Medicine (TCM), has been proved to be clinically useful in cardiomyopathy and inflammatory bowel diseases. However, the role and mechanism of SND in colitis-associated cancer remains unclear. This study aims to evaluate the effect of SND on colorectal cancer(CRC) symptoms and further explore the changes of gut microbes mediated by SND extract in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mice through 16 S rRNA sequencing. Our results indicated that treatment with SND extract could ameliorate the tumors' malignant degree by decreasing tumor number and size. Also, the expression levels of Cyclooxygenase 2 and Mucin-2, which are typical CRC biomarkers, were reduced compared to the CRC group. In the meantime, SND extract can upregulate CD8+ T lymphocytes' expression and Occludin in the colonic mucosal layer. Besides, SND inhibited the expression of CD4+ T cells and inflammatory cytokines in CRC tissue. According to bioinformatics analysis, SND extract was also suggested could modulate the gut microbial community. After the SND treatment, compared with the CRC mice model, the number of pathogenic bacteria showed a significant reduction, including Bacteroides fragilis and Sulphate-reducing bacteria; and SND increased the relative contents of the beneficial bacteria, including Lactobacillus, Bacillus coagulans, Akkermansia muciniphila, and Bifidobacterium. In summary, SND can effectively intervene in colorectal cancer development by regulating intestinal immunity, protecting the colonic mucosal barrier, and SND can change the intestinal microbiota composition in mice.

scholarly journals In-depth characterization of the serum antibody epitope repertoire in inflammatory bowel disease using phage-displayed immunoprecipitation sequencing

2021 ◽  
Author(s):  
Arno R. Bourgonje ◽  
Sergio Andreu-Sánchez ◽  
Thomas Vogl ◽  
Shixian Hu ◽  
Arnau Vich Vila ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Serum Antibody ◽  
Comprehensive Overview ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Antibody Epitope ◽  
Food Antigens ◽  
Bowel Diseases ◽  
Antibody Positivity ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD), e.g. Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. We leveraged a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow to identify antibodies against 344,000 antimicrobial, immune and food antigens in 497 IBD patients as compared to 1,326 controls. IBD was characterized by 373 differentially abundant antibodies (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD and 28% unique to UC. Antibodies against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (AUC=0.89), and similar discrimination was achieved when using only ten antibodies (AUC=0.87). IBD patients thus show a distinct antibody repertoire against selected peptides, allowing patient stratification and discovery of immunological targets.

scholarly journals Obstructive Sleep Apnea and Inflammation: Proof of Concept Based on Two Illustrative Cytokines

2019 ◽  
Vol 20 (3) ◽  
pp. 459 ◽  
Author(s):  
Leila Kheirandish-Gozal ◽  
David Gozal
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Inflammatory Diseases ◽  
Sleep Apnea Syndrome ◽  
Special Focus ◽  
Normal Body Mass Index ◽  
Low Grade ◽  
Obstructive Sleep ◽  
Inflammatory Processes ◽  
Factor Α

Obstructive sleep apnea syndrome (OSAS) is a markedly prevalent condition across the lifespan, particularly in overweight and obese individuals, which has been associated with an independent risk for neurocognitive, behavioral, and mood problems as well as cardiovascular and metabolic morbidities, ultimately fostering increases in overall mortality rates. In adult patients, excessive daytime sleepiness (EDS) is the most frequent symptom leading to clinical referral for evaluation and treatment, but classic EDS features are less likely to be reported in children, particularly among those with normal body-mass index. The cumulative evidence collected over the last two decades supports a conceptual framework, whereby sleep-disordered breathing in general and more particularly OSAS should be viewed as low-grade chronic inflammatory diseases. Accordingly, it is assumed that a proportion of the morbid phenotypic signature in OSAS is causally explained by underlying inflammatory processes inducing end-organ dysfunction. Here, the published links between OSAS and systemic inflammation will be critically reviewed, with special focus on the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), since these constitute classical prototypes of the large spectrum of inflammatory molecules that have been explored in OSAS patients.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

scholarly journals The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7506
Author(s):  
Charles Gwellem Anchang ◽  
Cong Xu ◽  
Maria Gabriella Raimondo ◽  
Raja Atreya ◽  
Andreas Maier ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Standard Of Care ◽  
Incidence Rates ◽  
Irreversible Damage ◽  
Omics Technologies ◽  
Progressive Development ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Affected Tissue ◽  
Systemic Nature

Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40–60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as “the great hope” for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from “bench to bedside” and the implementation into general patient care procedures.

scholarly journals Mutant glucocorticoid receptor binding elements on the interleukin-6 promoter regulate dexamethasone effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wen-Teng Chang ◽  
Ming-Yuan Hong ◽  
Chien-Liang Chen ◽  
Chi-Yuan Hwang ◽  
Cheng-Chieh Tsai ◽  
...  
Keyword(s):  
Binding Sites ◽  
Inflammatory Diseases ◽  
Inducible Promoter ◽  
Transcriptional Factor ◽  
Factor Binding ◽  
Inflammatory Processes ◽  
Nuclear Receptor Family ◽  
Specificity Protein ◽  
Receptor Family ◽  
Pro Inflammatory Cytokines

Abstract Background Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. Results Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1–2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. Conclusions We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.

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