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      Effects of Non-Starch Polysaccharides on Inflammatory Bowel Disease

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          Abstract

          The incidence of inflammatory bowel disease (IBD) has increased considerably over the past few decades. In the present review, we discuss several disadvantages existing in the treatment of IBD and current understandings of the structures, sources, and natures of various kinds of non-starch polysaccharides (NSPs). Available evidences for the use of different sources of NSPs in IBD treatment both in vitro and in vivo are analyzed, including glucan from oat bran, mushroom, seaweed, pectin, gum, prebiotics, etc. Their potential mechanisms, especially their related molecular mechanism of protective action in the treatment and prevention of IBD, are also summarized, covering the anti-inflammation, immune-stimulating, and gut microbiota-modulating activities, as well as short-chain fatty acids (SCFAs) production, anti-oxidative stress accompanied with inflammation, the promotion of gastric epithelial cell proliferation and tissue healing, and the reduction of the absorption of toxins of NSPs, thus ameliorating the symptoms and reducing the reoccurrence rate of IBD. In summary, NSPs exhibit the potential to be promising agents for an adjuvant therapy and for the prevention of IBD. Further investigating of the crosstalk between immune cells, epithelial cells, and gut microorganisms in addition to evaluating the effects of different kinds and different molecular weights of NSPs will lead to well-designed clinical intervention trials and eventually improve the treatment and prevention of IBD.

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          Most cited references115

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          Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation.

          Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 microm) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca2+ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.
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            Inflammatory bowel disease: clinical aspects and established and evolving therapies.

            Crohn's disease and ulcerative colitis are two idiopathic inflammatory bowel disorders. In this paper we discuss the current diagnostic approach, their pathology, natural course, and common complications, the assessment of disease activity, extraintestinal manifestations, and medical and surgical management, and provide diagnostic and therapeutic algorithms. We critically review the evidence for established (5-aminosalicylic acid compounds, corticosteroids, immunomodulators, calcineurin inhibitors) and emerging novel therapies--including biological therapies--directed at cytokines (eg, infliximab, adalimumab, certolizumab pegol) and receptors (eg, visilizumab, abatacept) involved in T-cell activation, selective adhesion molecule blockers (eg, natalizumab, MLN-02, alicaforsen), anti-inflammatory cytokines (eg, interleukin 10), modulation of the intestinal flora (eg, antibiotics, prebiotics, probiotics), leucocyte apheresis and many more monoclonal antibodies, small molecules, recombinant growth factors, and MAP kinase inhibitors targeting various inflammatory cells and pathways. Finally, we summarise the practical aspects of standard therapies including dosing, precautions, and side-effects.
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              Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity.

              Gut microbial dysbioses are linked to aberrant immune responses, which are often accompanied by abnormal production of inflammatory cytokines. As part of the Human Functional Genomics Project (HFGP), we investigate how differences in composition and function of gut microbial communities may contribute to inter-individual variation in cytokine responses to microbial stimulations in healthy humans. We observe microbiome-cytokine interaction patterns that are stimulus specific, cytokine specific, and cytokine and stimulus specific. Validation of two predicted host-microbial interactions reveal that TNFα and IFNγ production are associated with specific microbial metabolic pathways: palmitoleic acid metabolism and tryptophan degradation to tryptophol. Besides providing a resource of predicted microbially derived mediators that influence immune phenotypes in response to common microorganisms, these data can help to define principles for understanding disease susceptibility. The three HFGP studies presented in this issue lay the groundwork for further studies aimed at understanding the interplay between microbial, genetic, and environmental factors in the regulation of the immune response in humans. PAPERCLIP.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 June 2017
                July 2017
                : 18
                : 7
                : 1372
                Affiliations
                [1 ]Laboratory of Molecular Nutrition, College of Food science and Engineering, National Engineering Laboratory for Deep Processing of Rice and Byproducts, Central South University of Forestry and Technology, Changsha 410004, China; ny198722@ 123456hotmail.com (Y.N.); linqinlu@ 123456hotmail.com (Q.L.)
                [2 ]Department of Animal Science and Technology, College of Hunan Biological and Electromechanical Polytechnic, Changsha 410128, China
                Author notes
                [* ]Correspondence: luofeijun888@ 123456csuft.edu.cn or luofeijun@ 123456hotmail.com ; Tel.: +86-731-8562-3240
                [†]

                These authors contribute equally to this work.

                Article
                ijms-18-01372
                10.3390/ijms18071372
                5535865
                28654020
                05566574-109e-44dc-9aea-f5f89beb921e
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 May 2017
                : 18 June 2017
                Categories
                Review

                Molecular biology
                non-starch polysaccharide (nsp),inflammatory bowel disease (ibd),intervention,mechanism,scfas,gut microbiota,immune system,pro-inflammatory cytokines

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