scholarly journals An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3202
Author(s):  
Rafał Filip

Some of the most fundamental influences of microorganisms inhabiting the human intestinal tract are exerted during infant development and impact the maturation of intestinal mucosa and gut immune system. The impact of bacteria on the host gut immune system is partially mediated via released extracellular vesicles (EVs). The heterogeneity in EV content, size, and bacterial species origin can have an impact on intestinal cells, resulting in inflammation and an immune response, or facilitate pathogen entry into the gut wall. In mammals, maintaining the integrity of the gut barrier might also be an evolutionary function of maternal milk EVs. Recently, the usage of EVs has been explored as a novel therapeutic approach in several pathological conditions, including necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). In this review, we attempt to summarize the current knowledge of EV biology, followed by a discussion of the role that EVs play in gut maturation and the pathogenesis of NEC and IBD.

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1387
Author(s):  
Lorenzo Bertani ◽  
Davide Giuseppe Ribaldone ◽  
Massimo Bellini ◽  
Maria Gloria Mumolo ◽  
Francesco Costa

Nutrition has an important impact on inflammatory bowel diseases (IBD). In particular, several studies have addressed its role in their pathogenesis, showing how the incidence of IBD significantly increased in recent years. Meanwhile, nutrition should be considered a component of the treatment of the disease, both as a therapy itself, and especially in the perspective of correcting the various nutritional deficiencies shown by these patients. In this perspective, nutritional suggestions are very important even in the most severe forms of IBD, requiring hospitalization or surgical treatment. Although current knowledge about nutrition in IBD is increasing over time, nutritional suggestions are often underestimated by clinicians. This narrative review is an update summary of current knowledge on nutritional suggestions in IBD, in order to address the impact of nutrition on pathogenesis, micro- and macro-nutrients deficiencies (especially in the case of sarcopenia and obesity), as well as in hospitalized patients.


Author(s):  
Vibeke Andersen ◽  
Axel Kornerup Hansen ◽  
Berit Lilienthal Heitmann

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.


2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.


Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 260
Author(s):  
Adelaide Teofani ◽  
Irene Marafini ◽  
Federica Laudisi ◽  
Daniele Pietrucci ◽  
Silvia Salvatori ◽  
...  

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn’s disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables “age”, “eat yogurt at least four days per week” and “eat dairy products at least 4 days per week” as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables “age”, “gender”, “eat meat at least four days per week” and “eat bread at least 4 days per week” were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour.


2021 ◽  
Author(s):  
Shijie He ◽  
Peng Lei ◽  
Wenying Kang ◽  
Priscilla Cheung ◽  
Tao Xu ◽  
...  

SummaryDoes fibrotic gut stiffening caused by inflammatory bowel diseases (IBD) direct the fate of intestinal stem cells (ISCs)? To address this question we first developed a novel long-term culture of quasi-3D gut organoids plated on hydrogel matrix of varying stiffness. Stiffening from 0.6kPa to 9.6kPa significantly reduces Lgr5high ISCs and Ki67+ progenitor cells while promoting their differentiation towards goblet cells. These stiffness-driven events are attributable to YAP nuclear translocation. Matrix stiffening also extends the expression of the stemness marker Olfactomedin 4 (Olfm4) into villus-like regions, mediated by cytoplasmic YAP. We next used single-cell RNA sequencing to generate for the first time the stiffness-regulated transcriptional signatures of ISCs and their differentiated counterparts. These signatures confirm the impact of stiffening on ISC fate and additionally suggest a stiffening-induced switch in metabolic phenotype, from oxidative phosphorylation to glycolysis. Finally, we used colon samples from IBD patients as well as chronic colitis murine models to confirm the in vivo stiffening-induced epithelial deterioration similar to that observed in vitro. Together, these results demonstrate stiffness-dependent ISC reprograming wherein YAP nuclear translocation diminishes ISCs and Ki67+ progenitors and drives their differentiation towards goblet cells, suggesting stiffening as potential target to mitigate gut epithelial deterioration during IBD.


2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Beatriz Mateos ◽  
Cora Palanca-Ballester ◽  
Esteban Saez-Gonzalez ◽  
Inés Moret ◽  
Adrian Lopez ◽  
...  

Abstract Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.


2020 ◽  
Vol 26 (12) ◽  
pp. 1787-1795 ◽  
Author(s):  
Mariana Ferreira-Duarte ◽  
Maria Manuela Estevinho ◽  
Margarida Duarte-Araújo ◽  
Fernando Magro ◽  
Manuela Morato

Abstract Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S280-S281
Author(s):  
M Attauabi ◽  
M Zhao ◽  
F Bendtsen ◽  
J Burisch

Abstract Background Several studies have shown an association between inflammatory bowel diseases [IBD] and immune-mediated diseases [IMIDs], but data on the impact of co-occurring IMIDs on IBD course are inconsistent. The aim of this study was to investigate the impact of co-occurring IMIDs on IBD phenotype and disease course. Methods PubMed and EMBASE were searched from database inception through December 2018 and updated in October 2019 for studies reporting prevalences or odds, risks or hazard ratios of IBD-related disease outcomes in patients with and without co-existing IMIDs. Meta-analyses were performed to estimate summary prevalences and risks of the outcomes which included disease extension, IBD-related surgery and hospitalisation, malignancy, mortality and need of medication (biologic therapy, steroids and immunomodulators). IMIDs were stratified into primary sclerosing cholangitis [PSC] and ‘IMIDs other than PSC’. Results A total of 93 studies comprising 14,307 IBD patients with IMIDs and 3,409,914 IBD patients without IMIDs were included in the study. Summary risks and prevalences with 95% confidence intervals for each outcome are presented in figures 1 and 2, respectively. The following results are all significant (p < 0.05). Compared with patients without co-occurring IMIDs, patients with ulcerative colitis [UC] and co-occurring IMIDs other than PSC more frequently received immunomodulators and steroids, and patients with Crohn’s disease [CD] and concomitant IMIDs other than PSC more often received biologic therapy. UC patients with co-existing IMIDs other than PSC more often underwent IBD-related surgery, while patients with CD and PSC received fewer surgeries. In addition, UC patients with co-occurring PSC were at increased risk for having extensive colitis, pancolitis, and malignancies. Patients with UC and PSC had a higher mortality rate, but no difference was found among patients with IMIDs other than PSC. PSC did not influence hospitalisation rates among IBD patients. Conclusion This meta-analysis found that IBD patients with co-existing IMIDs have a different disease course than patients without concomitant IMIDs. This study emphasises the importance of multidisciplinary care of IBD and that physicians caring for IBD patients need to be aware of IMIDs as a prognostic factor.


2020 ◽  
Vol 21 (12) ◽  
pp. 4223 ◽  
Author(s):  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Tiziana Genovese ◽  
Salvatore Cuzzocrea ◽  
Rosanna Di Paola

Inflammation is a protective reaction activated in response to detrimental stimuli, such as dead cells, irritants or pathogens, by the evolutionarily conserved immune system and is regulated by the host. The inflammasomes are recognized as innate immune system sensors and receptors that manage the activation of caspase-1 and stimulate inflammation response. They have been associated with several inflammatory disorders. The NLRP3 inflammasome is the most well characterized. It is so called because NLRP3 belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent evidence has greatly improved our understanding of the mechanisms by which the NLRP3 inflammasome is activated. Additionally, increasing data in animal models, supported by human studies, strongly implicate the involvement of the inflammasome in the initiation or progression of disorders with a high impact on public health, such as metabolic pathologies (obesity, type 2 diabetes, atherosclerosis), cardiovascular diseases (ischemic and non-ischemic heart disease), inflammatory issues (liver diseases, inflammatory bowel diseases, gut microbiome, rheumatoid arthritis) and neurologic disorders (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and other neurological disorders), compared to other molecular platforms. This review will provide a focus on the available knowledge about the NLRP3 inflammasome role in these pathologies and describe the balance between the activation of the harmful and beneficial inflammasome so that new therapies can be created for patients with these diseases.


2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Anouk Waeytens ◽  
Martine De Vos ◽  
Debby Laukens

Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their pathogenesis. Metallothioneins (MTs) are a family of small proteins with a high and conserved cysteine content that are rapidly upregulated in response to an inflammatory stimulus. Herein, we review the current knowledge regarding the expression and potential role of MTs in IBD. MTs exert a central position in zinc homeostasis, modulate the activation of the transcription factor nuclear factor (NF)-B, and serve as antioxidants. In addition, MTs could be involved in IBD through their antiapoptotic effects or through specific immunomodulating extracellular effects. Reports on MT expression in IBD are contradictory but clearly demonstrate a deviant MT expression supporting the idea that these aberrations in IBD require further clarification.


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