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      Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

      review-article
      1 , , 2
      Gut
      BMJ Publishing Group
      inflammatory bowel disease, diet, gut inflammation, dietary factors, intestinal microbiology

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          Abstract

          The diet and gut microbiota have been extensively interrogated as a fuel for gut inflammation in inflammatory bowel diseases (IBDs) in the last few years. Here, we review how specific nutrients, typically enriched in a Western diet, instigate or deteriorate experimental gut inflammation in a genetically susceptible host and we discuss microbiota-dependent and independent mechanisms. We depict the study landscape of nutritional trials in paediatric and adult IBD and delineate common grounds for dietary advice. Conclusively, the diet reflects a critical rheostat of microbial dysbiosis and gut inflammation in IBD. Dietary restriction by exclusive enteral nutrition, with or without a specific exclusion diet, is effectively treating paediatric Crohn’s disease, while adult IBD trials are less conclusive. Insights into molecular mechanisms of nutritional therapy will change the perception of IBD and will allow us to enter the era of precision nutrition. To achieve this, we discuss the need for carefully designed nutritional trials with scientific rigour comparable to medical trials, which also requires action from stake holders. Establishing evidence-based dietary therapy for IBD does not only hold promise to avoid long-term immunosuppression, but to provide a widely accessible therapy at low cost. Identification of dietary culprits disturbing gut health also bears the potential to prevent IBD and allows informed decision making in food politics.

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          Most cited references159

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          Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

          Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
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            Diet rapidly and reproducibly alters the human gut microbiome

            Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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              Linking long-term dietary patterns with gut microbial enterotypes.

              Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                December 2022
                16 September 2022
                : 71
                : 12
                : 2574-2586
                Affiliations
                [1 ] departmentDepartment of Medicine I, Gastroenterology, Hepatology & Metabolism , Medical University Innsbruck , Innsbruck, Austria
                [2 ] departmentDepartment of Medicine & Therapeutics , The Chinese University of Hong Kong , Hong Kong, Hong Kong
                Author notes
                [Correspondence to ] Dr Timon E Adolph, Medical University of Innsbruck, Innsbruck 6020, Austria; timon-erik.adolph@ 123456i-med.ac.at
                Author information
                http://orcid.org/0000-0002-4736-830X
                http://orcid.org/0000-0002-0344-3398
                Article
                gutjnl-2021-326575
                10.1136/gutjnl-2021-326575
                9664119
                36113981
                3ab3dba0-25ed-4ce9-99a0-8d79d85b2e24
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 10 April 2022
                : 01 September 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Categories
                Recent Advances in Basic Science
                1506
                2312
                1239
                Custom metadata
                unlocked

                Gastroenterology & Hepatology
                inflammatory bowel disease,diet,gut inflammation,dietary factors,intestinal microbiology

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