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      Connecting the Dots Between Inflammatory Bowel Disease and Metabolic Syndrome: A Focus on Gut-Derived Metabolites

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          Abstract

          The role of the microbiome in health and disease has gained considerable attention and shed light on the etiology of complex diseases like inflammatory bowel disease (IBD) and metabolic syndrome (MetS). Since the microorganisms inhabiting the gut can confer either protective or harmful signals, understanding the functional network between the gut microbes and the host provides a comprehensive picture of health and disease status. In IBD, disruption of the gut barrier enhances microbe infiltration into the submucosae, which enhances the probability that gut-derived metabolites are translocated from the gut to the liver and pancreas. Considering inflammation and the gut microbiome can trigger intestinal barrier dysfunction, risk factors of metabolic diseases such as insulin resistance may have common roots with IBD. In this review, we focus on the overlap between IBD and MetS, and we explore the role of common metabolites in each disease in an attempt to connect a common origin, the gut microbiome and derived metabolites that affect the gut, liver and pancreas.

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          Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health

          The colon is inhabited by a dense population of microorganisms, the so-called “gut microbiota,” able to ferment carbohydrates and proteins that escape absorption in the small intestine during digestion. This microbiota produces a wide range of metabolites, including short chain fatty acids (SCFA). These compounds are absorbed in the large bowel and are defined as 1-6 carbon volatile fatty acids which can present straight or branched-chain conformation. Their production is influenced by the pattern of food intake and diet-mediated changes in the gut microbiota. SCFA have distinct physiological effects: they contribute to shaping the gut environment, influence the physiology of the colon, they can be used as energy sources by host cells and the intestinal microbiota and they also participate in different host-signaling mechanisms. We summarize the current knowledge about the production of SCFA, including bacterial cross-feedings interactions, and the biological properties of these metabolites with impact on the human health.
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            The microbiome in inflammatory bowel disease: current status and the future ahead.

            Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases.

              Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response. Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29). The faecal microbiota composition was assessed by quantitative real-time PCR. Using BA profiles and microbiota composition, cluster formation between groups was generated by ranking models. The faecal BA profiles in germ-free and conventional mice were compared. Direct enzymatic activities of BA biotransformation were measured in faeces. The impact of BA on the inflammatory response was investigated in vitro using Caco-2 cells stimulated by IL-1β. IBD-associated dysbiosis was characterised by a decrease in the ratio between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA rates were significantly higher in active IBD, whereas, secondary BA rates were significantly lower. Interestingly, active IBD patients exhibited higher levels of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation activities of the microbiota were impaired in IBD patients. In vitro, secondary BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished their anti-inflammatory properties. Impaired microbiota enzymatic activity observed in IBD-associated dysbiosis leads to modifications in the luminal BA pool composition. Altered BA transformation in the gut lumen can erase the anti-inflammatory effects of some BA species on gut epithelial cells and could participate in the chronic inflammation loop of IBD.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                15 May 2020
                May 2020
                : 12
                : 5
                : 1434
                Affiliations
                [1 ]Department of Biology, University of British Columbia, Okanagan campus, Kelowna, BC V6T 1Z4, Canada; averdugo@ 123456mail.ubc.ca (A.V.-M.); jiayu.ye@ 123456ubc.ca (J.Y.); hansikadadlani9@ 123456gmail.com (H.D.)
                [2 ]Department of Medicine, University of British Columbia, Okanagan campus, Kelowna, BC V1V 1V7, Canada
                Author notes
                [* ]Correspondence: Sanjoy.Ghosh@ 123456ubc.ca (S.G.); Deanna.Gibson@ 123456ubc.ca (D.L.G.); Tel.: +1250-807-8790 (D.L.G.)
                [†]

                Co-first authorship.

                Author information
                https://orcid.org/0000-0003-0052-7550
                Article
                nutrients-12-01434
                10.3390/nu12051434
                7285036
                32429195
                74afa5aa-fb5a-4e37-9359-79347ad27121
                © 2020 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
                : 21 April 2020
                : 13 May 2020
                Categories
                Review

                Nutrition & Dietetics
                immunometabolism,gut microbiome,microbiomics,insulin resistance,metabolism,inflammatory bowel disease

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