Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

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.

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Effects of Boswellia serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

10.20944/preprints201807.0317.v1 ◽

2018 ◽

Author(s):

Paolo Governa ◽

Maddalena Marchi ◽

Veronica Cocetta ◽

Bianca De Leo ◽

Philippa T. K. Saunders ◽

...

Keyword(s):

Mechanism Of Action ◽

Immune Cells ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Curcuma Longa ◽

Intestinal Barrier Function ◽

Boswellia Serrata ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the use of herbal therapies has increased in patients with inflammatory bowel diseases because of their effectiveness and better safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two standardized extract of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with C. longa having an anti-inflammatory mechanism of action and B. serrata acting as an antioxidant. In summary, these herbal products were demonstrated to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

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Immunomodulatory Effects of Flavonoids in the Prophylaxis and Treatment of Inflammatory Bowel Diseases: A Comprehensive Review

Current Medicinal Chemistry ◽

10.2174/0929867325666180214121734 ◽

2018 ◽

Vol 25 (28) ◽

pp. 3374-3412 ◽

Cited By ~ 3

Author(s):

Daniela Ribeiro ◽

Carina Proenca ◽

Silvia Rocha ◽

Jose L.F.C. Lima ◽

Felix Carvalho ◽

...

Keyword(s):

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Biological Properties ◽

Human Diet ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Inflammatory Bowel Diseases (IBD) comprised of two disorders of idiopathic chronic intestinal inflammation that affect about three million people worldwide: Crohn’s disease and ulcerative colitis. Nowadays, the first-line of treatment for patients with mild to moderate symptoms of IBD is comprised of corticosteroids, immunosuppressants, antibiotics, and biological agents. Unfortunately, none of these drugs are curative, and their long-term use may cause severe side effects and complications. Almost 40% of IBD patients use alternative therapies to complement the conventional one, and flavonoids are gaining attention for this purpose. The biological properties of flavonoids are well documented and their antioxidant and anti-inflammatory activities have been arousing attention in the scientific community. Flavonoids are the most widely distributed polyphenols in plants and fruits, making part of the human diet. Taking into account that all ingested flavonoids are expected to exert biological actions at the gastrointestinal level, research on the modulatory effect of these compounds in IBD is of paramount importance. This review intends to summarize, in an integrated and comprehensive form, the effect of flavonoids, both in vitro and in vivo, in the different phases of the characteristic IBD inflammatory network.

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Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

Science Translational Medicine ◽

10.1126/scitranslmed.aaz4047 ◽

2020 ◽

Vol 12 (560) ◽

pp. eaaz4047

Author(s):

Antoine P. Fournier ◽

Sara Martinez de Lizarrondo ◽

Adrien Rateau ◽

Axel Gerard-Brisou ◽

Maximilian J. Waldner ◽

...

Keyword(s):

Adhesion Molecule ◽

Intestinal Mucosa ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Mucosal Inflammation ◽

Molecular Mri ◽

Mucosal Tissues ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

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Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

Precision Clinical Medicine ◽

10.1093/pcmedi/pbab025 ◽

2021 ◽

Author(s):

Huimin Chen ◽

Xiaohan Wu ◽

Chunjin Xu ◽

Jian Lin ◽

Zhanju Liu

Keyword(s):

Immune Cells ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Critical Role ◽

Mucosal Inflammation ◽

Repair Processes ◽

Microbial Invasion ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation and provide a precise overview of neutrophil functions in the pathogenesis of IBD.

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Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

Pharmaceuticals ◽

10.3390/ph11040126 ◽

2018 ◽

Vol 11 (4) ◽

pp. 126 ◽

Cited By ~ 9

Author(s):

Paolo Governa ◽

Maddalena Marchi ◽

Veronica Cocetta ◽

Bianca De Leo ◽

Philippa Saunders ◽

...

Keyword(s):

Mechanism Of Action ◽

Immune Cells ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Curcuma Longa ◽

Intestinal Barrier Function ◽

Boswellia Serrata ◽

Bowel Diseases ◽

Inflammatory Bowel

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favourable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/mL, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H2O2-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

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Renin‐angiotensin system in intestinal inflammation – Angiotensin inhibitors to treat inflammatory bowel diseases?

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.13624 ◽

2021 ◽

Author(s):

Hanne Salmenkari ◽

Riitta Korpela ◽

Heikki Vapaatalo

Keyword(s):

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Bowel Diseases ◽

Inflammatory Bowel

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Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22052645 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2645

Author(s):

Dinh Nam Tran ◽

Seon Myeong Go ◽

Seon-Mi Park ◽

Eui-Man Jung ◽

Eui-Bae Jeung

Keyword(s):

Immune Response ◽

Cellular Proliferation ◽

Intestinal Inflammation ◽

Critical Role ◽

Experimental Colitis ◽

Innate Immune ◽

Inflammatory Conditions ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

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Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

Gastroenterology Research and Practice ◽

10.1155/2015/189341 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Luca Pastorelli ◽

Elena Dozio ◽

Laura Francesca Pisani ◽

Massimo Boscolo-Anzoletti ◽

Elena Vianello ◽

...

Keyword(s):

Inflammatory Bowel Diseases ◽

Intestinal Barrier ◽

Systemic Circulation ◽

Intestinal Barrier Function ◽

Inflammatory Conditions ◽

Immune Mediated ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Molecular Patterns ◽

D Dimer

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.

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