scholarly journals Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2253
Author(s):  
Miguel Gonzalez Acera ◽  
Marvin Bubeck ◽  
Fabrizio Mascia ◽  
Leonard Diemand ◽  
Gregor Sturm ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.

2008 ◽  
Vol 20 (9) ◽  
pp. 1009-1016 ◽  
Author(s):  
v. villanacci ◽  
g. bassotti ◽  
r. nascimbeni ◽  
e. antonelli ◽  
m. cadei ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.


2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.


2021 ◽  
Vol 14 ◽  
pp. 175628482110531
Author(s):  
Henit Yanai ◽  
Hadar Amir Barak ◽  
Jacob E Ollech ◽  
Irit Avni Biron ◽  
Idan Goren ◽  
...  

Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age – 35.2 ± 13.5 years, disease duration – 7.1 (interquartile range: 3.7–13.9) years; Crohn’s disease – 94/118 (79.6%). Skin eruption induced by an anti–tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) – 31/46 (67.4%) and inflammatory alopecia (IA) – 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P = .09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS). Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab.


2012 ◽  
Vol 30 (3) ◽  
pp. 289-295 ◽  
Author(s):  
Gábor Lakatos ◽  
István Hritz ◽  
Mária Zsófia Varga ◽  
Márk Juhász ◽  
Pál Miheller ◽  
...  

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