Review Am J Physiol Gastrointest Liver Physiol
. 2020 Nov 1;319(5):G589-G608. doi: 10.1152/ajpgi.00245.2020. Epub 2020 Sep 9.
Effects of dietary components on intestinal permeability in health and disease
Katayoun Khoshbin 1, Michael Camilleri 1
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PMID: 32902315 PMCID: PMC8087346 DOI: 10.1152/ajpgi.00245.2020
Abstract
Altered intestinal permeability plays a role in many pathological conditions. Intestinal permeability is a component of the intestinal barrier. This barrier is a dynamic interface between the body and the food and pathogens that enter the gastrointestinal tract. Therefore, dietary components can directly affect this interface, and many metabolites produced by the host enzymes or the gut microbiota can act as signaling molecules or exert direct effects on this barrier. Our aim was to examine the effects of diet components on the intestinal barrier in health and disease states. Herein, we conducted an in-depth PubMed search based on specific key words (diet, permeability, barrier, health, disease, and disorder), as well as cross references from those articles. The normal intestinal barrier consists of multiple components in the lumen, epithelial cell layer and the lamina propria. Diverse methods are available to measure intestinal permeability. We focus predominantly on human in vivo studies, and the literature is reviewed to identify dietary factors that decrease (e.g., emulsifiers, surfactants, and alcohol) or increase (e.g., fiber, short-chain fatty acids, glutamine, and vitamin D) barrier integrity. Effects of these dietary items in disease states, such as metabolic syndrome, liver disease, or colitis are documented as examples of barrier dysfunction in the multifactorial diseases. Effects of diet on intestinal barrier function are associated with precise mechanisms in some instances; further research of those mechanisms has potential to clarify the role of dietary interventions in treating diverse pathologic states.
Keywords: diet; food; gut barrier; microbiota; nutrition.
Conflict of interest statement
No conflicts of interest, financial or otherwise, are declared by the authors.
Cited by 51 articles200 references5 figures
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Review BMC Gastroenterol
. 2014 Nov 18:14:189. doi: 10.1186/s12876-014-0189-7.
Intestinal permeability--a new target for disease prevention and therapy
Stephan C Bischoff, Giovanni Barbara, Wim Buurman, Theo Ockhuizen, Jörg-Dieter Schulzke, Matteo Serino, Herbert Tilg, Alastair Watson, Jerry M Wells
PMID: 25407511 PMCID: PMC4253991 DOI: 10.1186/s12876-014-0189-7
Abstract
Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms 'intestinal barrier' and 'intestinal permeability' are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by 'intestinal permeability'. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and--more recently recognized--obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.
Cited by 625 articles265 references7 figures
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Review Curr Opin Clin Nutr Metab Care
. 2017 Jan;20(1):86-91. doi: 10.1097/MCO.0000000000000339.
Glutamine and the regulation of intestinal permeability: from bench to bedside
Najate Achamrah 1, Pierre Déchelotte, Moïse Coëffier
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PMID: 27749689 DOI: 10.1097/MCO.0000000000000339
Abstract
Purpose of review: Glutamine is the most abundant amino acid in plasma and plays a key role in maintaining the integrity of intestinal barrier.
Recent findings: Experimental studies showed that glutamine is able to modulate intestinal permeability and tight junction protein expression in several conditions. Recent articles underlined its putative beneficial role in gastrointestinal disorders such as irritable bowel syndrome.
Summary: Glutamine is a major nutrient to maintain intestinal barrier function in animals and humans. Depletion of glutamine results in villus atrophy, decreased expression of tight junction proteins and increased intestinal permeability. Moreover, glutamine supplementation can improve gut barrier function in several experimental conditions of injury and in some clinical situations. Furthermore, preventive effects of glutamine in experimental models of intestinal injuries have been recently reported. Despite promising data in experimental models, further studies are needed to evaluate glutamine supplementation in clinical practice.
Cited by 22 articles
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Review Front Nutr
. 2021 Aug 26:8:717925. doi: 10.3389/fnut.2021.717925. eCollection 2021.
The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation
Tim Vanuytsel 1 2, Jan Tack 1 2, Ricard Farre 1
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PMID: 34513903 PMCID: PMC8427160 DOI: 10.3389/fnut.2021.717925
Abstract
An increased intestinal permeability has been described in various gastrointestinal and non-gastrointestinal disorders. Nevertheless, the concept and definition of intestinal permeability is relatively broad and includes not only an altered paracellular route, regulated by tight junction proteins, but also the transcellular route involving membrane transporters and channels, and endocytic mechanisms. Paracellular intestinal permeability can be assessed in vivo by using different molecules (e.g., sugars, polyethylene glycols, 51Cr-EDTA) and ex vivo in Ussing chambers combining electrophysiology and probes of different molecular sizes. The latter is still the gold standard technique for assessing the epithelial barrier function, whereas in vivo techniques, including putative blood biomarkers such as intestinal fatty acid-binding protein and zonulin, are broadly used despite limitations. In the second part of the review, the current evidence of the role of impaired barrier function in the pathophysiology of selected gastrointestinal and liver diseases is discussed. Celiac disease is one of the conditions with the best evidence for impaired barrier function playing a crucial role with zonulin as its proposed regulator. Increased permeability is clearly present in inflammatory bowel disease, but the question of whether this is a primary event or a consequence of inflammation remains unsolved. The gut-liver axis with a crucial role in impaired intestinal barrier function is increasingly recognized in chronic alcoholic and metabolic liver disease. Finally, the current evidence does not support an important role for increased permeability in bile acid diarrhea.
Keywords: GI diseases; bile acid malabsorption; chronic liver disease; coeliac disease; inflammatory bowel disease; intestinal permeability; paracellular route; transcellular route.
Copyright © 2021 Vanuytsel, Tack and Farre.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Cited by 51 articles179 references2 figures
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Review Neurogastroenterol Motil
. 2012 Jun;24(6):503-12. doi: 10.1111/j.1365-2982.2012.01921.x.
Intestinal barrier function in health and gastrointestinal disease
M Camilleri 1, K Madsen, R Spiller, B Greenwood-Van Meerveld, G N Verne
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PMID: 22583600 PMCID: PMC5595063 DOI: 10.1111/j.1365-2982.2012.01921.x
Erratum in
Neurogastroenterol Motil. 2012 Oct;24(10):976. Van Meerveld, B G [corrected to Greenwood-Van Meerveld, B]
Abstract
Defects in intestinal barrier function are associated with diseases of the gastrointestinal (GI) tract. There is growing evidence that increases in intestinal permeability plays a pathogenic role in diseases, such as inflammatory bowel disease (IBD) and celiac disease, and functional bowel disorders, such as irritable bowel syndrome (IBS). This review takes a unique translational approach to discuss the physiological and pathophysiological mechanisms involved in the regulation of intestinal barrier function in IBS. The review summarizes the components of the intestinal barrier including the tight junction complex within the epithelium, and the methods used to assess gut permeability both in vitro and in vivo. Throughout the review, the authors have attempted to critically review the latest research from both experimental animal models and human studies to appraise whether intestinal barrier dysfunction is a primary cause of functional GI disorders, such as IBS.…
© 2012 Blackwell Publishing Ltd.
Comment in
Food and intestinal barrier function in irritable bowel syndrome.
Matuchansky C.
Neurogastroenterol Motil. 2012 Sep;24(9):888; author reply 889. doi: 10.1111/j.1365-2982.2012.01978.x.
PMID: 22908865 No abstract available.
Cited by 311 articles82 references1 figure
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Review Intern Emerg Med
. 2024 Mar;19(2):275-293. doi: 10.1007/s11739-023-03374-w. Epub 2023 Jul 28.
Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review
Federica Di Vincenzo 1 2, Angelo Del Gaudio 3 4, Valentina Petito 3, Loris Riccardo Lopetuso 3, Franco Scaldaferri 3 4
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PMID: 37505311 PMCID: PMC10954893 DOI: 10.1007/s11739-023-03374-w
Abstract
The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions.
Keywords: Gut microbiota; Intestinal barrier; Intestinal permeability; Metabolic disease; Systemic inflammation.
© 2023. The Author(s).
Conflict of interest statement
The authors have no conflict of interest to declare.
Cited by 12 articles82 references2 figures
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Review Anim Sci J
. 2020 Jan-Dec;91(1):e13357. doi: 10.1111/asj.13357.
Regulation of the intestinal barrier by nutrients: The role of tight junctions
Takuya Suzuki 1 2
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PMID: 32219956 PMCID: PMC7187240 DOI: 10.1111/asj.13357
Abstract
Tight junctions (TJs) play an important role in intestinal barrier function. TJs in intestinal epithelial cells are composed of different junctional molecules, such as claudin and occludin, and regulate the paracellular permeability of water, ions, and macromolecules in adjacent cells. One of the most important roles of the TJ structure is to provide a physical barrier to luminal inflammatory molecules. Impaired integrity and structure of the TJ barrier result in a forcible activation of immune cells and chronic inflammation in different tissues. According to recent studies, the intestinal TJ barrier could be regulated, as a potential target, by dietary factors to prevent and reduce different inflammatory disorders, although the precise mechanisms underlying the dietary regulation remain unclear. This review summarizes currently available information on the regulation of the intestinal TJ barrier by food components.
Keywords: intestinal barrier; intestinal permeability; nutrient; tight junction.
© 2020 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
Cited by 160 articles124 references1 figure
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Review Neurobiol Stress
. 2023 Oct 6:27:100579. doi: 10.1016/j.ynstr.2023.100579. eCollection 2023 Nov.
Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidence?
Danique La Torre 1 2, Lukas Van Oudenhove 1 2 3, Tim Vanuytsel 1 4, Kristin Verbeke 1
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PMID: 37842017 PMCID: PMC10569989 DOI: 10.1016/j.ynstr.2023.100579
Abstract
An impaired intestinal barrier function can be detrimental to the host as it may allow the translocation of luminal antigens and toxins into the subepithelial tissue and bloodstream. In turn, this may cause local and systemic immune responses and lead to the development of pathologies. In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans. In the current Review, we discuss the mechanisms that are involved in stress-induced intestinal permeability changes and postulate factors that influence these alterations and that may explain the translational difficulties from in vitro and animal to human studies. As human research differs highly from animal research in the extent to which stress can be applied and intestinal permeability can be measured, it remains difficult to draw conclusions about the presence of a relation between stress and intestinal permeability in (healthy) humans. Future studies should bear in mind these difficulties, and more research into in vivo methods to assess intestinal permeability are warranted.
Keywords: CRH; Cortisol; Intestinal permeability; Mast cells; Psychosocial stress.
© 2023 The Authors. Published by Elsevier Inc.
Conflict of interest statement
Authors D.L.T., L.V.O., T.V., and K.V. declare none.
116 references2 figures
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Review Am J Physiol Heart Circ Physiol
. 2020 Dec 1;319(6):H1227-H1233. doi: 10.1152/ajpheart.00612.2020. Epub 2020 Sep 28.
Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease
Caitlin V Lewis 1, W Robert Taylor 1 2 3
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PMID: 32986965 PMCID: PMC7792706 DOI: 10.1152/ajpheart.00612.2020
Abstract
The gut microbiome and intestinal dysfunction have emerged as potential contributors to the development of cardiovascular disease (CVD). Alterations in gut microbiome are well documented in hypertension, atherosclerosis, and heart failure and have been investigated as a therapeutic target. However, a perhaps underappreciated but related role for intestinal barrier function has become evident. Increased intestinal permeability is observed in patients and mouse models of CVD. This increased intestinal permeability can enhance systemic inflammation, alter gut immune function, and has been demonstrated as predictive of adverse cardiovascular outcomes. The goal of this review is to examine the evidence supporting a role for intestinal barrier function in cardiovascular disease and its prospect as a novel therapeutic target. We outline key studies that have investigated intestinal permeability in hypertension, coronary artery disease, atherosclerosis, heart failure, and myocardial infarction. We highlight the central mechanisms involved in the breakdown of barrier function and look at emerging evidence for restored barrier function as a contributor to promising treatment strategies such as short chain fatty acid, probiotic, and renin angiotensin system-targeted therapeutics. Recent studies of more selective targeting of the intestinal barrier to improve disease outcomes are also examined. We suggest that although current data supporting a contribution of intestinal permeability to CVD pathogenesis are largely associative, it appears to be a promising avenue for further investigation. Additional studies of the mechanisms of barrier restoration in CVD and testing of intestinal barrier-targeted compounds will be required to confirm their potential as a new class of CVD therapeutic.
Keywords: atherosclerosis; cardiovascular disease; gut microbiome; hypertension; intestinal permeability.