Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier

Intestinal tract is the boundary that prevents harmful molecules from invading into the mucosal tissue, followed by systemic circulation. Intestinal permeability is an index for intestinal barrier integrity. Intestinal permeability has been shown to increase in various diseases—not only intestinal inflammatory diseases, but also systemic diseases, including diabetes, chronic kidney dysfunction, cancer, and cardiovascular diseases. Chronic increase of intestinal permeability is termed ‘leaky gut’ which is observed in the patients and animal models of these diseases. This state often correlates with the disease state. In addition, recent studies have revealed that gut microbiota affects intestinal and systemic heath conditions via their metabolite, especially short-chain fatty acids and lipopolysaccharides, which can trigger leaky gut. The etiology of leaky gut is still unknown; however, recent studies have uncovered exogenous factors that can modulate intestinal permeability. Nutrients are closely related to intestinal health and permeability that are actively investigated as a hot topic of scientific research. Here, we will review the effect of nutrients on intestinal permeability and microbiome for a better understanding of leaky gut and a possible mechanism of increase in intestinal permeability.

Download Full-text

The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

PLoS ONE ◽

10.1371/journal.pone.0220642 ◽

2019 ◽

Vol 14 (8) ◽

pp. e0220642 ◽

Cited By ~ 9

Author(s):

Yuliia Holota ◽

Taisa Dovbynchuk ◽

Izumi Kaji ◽

Igor Vareniuk ◽

Natalia Dzyubenko ◽

...

Keyword(s):

Fatty Acids ◽

Antibiotic Therapy ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Barrier Integrity ◽

Intestinal Barrier Integrity ◽

Long Term Consequences

Download Full-text

Dietary Carbohydrates and Lipids in the Pathogenesis of Leaky Gut Syndrome: An Overview

International Journal of Molecular Sciences ◽

10.3390/ijms21218368 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8368

Author(s):

Agata Binienda ◽

Agata Twardowska ◽

Adam Makaro ◽

Maciej Salaga

Keyword(s):

Fatty Acids ◽

Intestinal Permeability ◽

Dietary Habits ◽

Short Chain Fatty Acids ◽

Incidence Rates ◽

Dietary Carbohydrates ◽

Leaky Gut ◽

Intestinal Membrane ◽

Junction Protein ◽

Chain Fatty Acids

This review summarizes the recent knowledge on the effects of dietary carbohydrates and lipids on the pathophysiology of leaky gut syndrome (LGS). Alterations in intestinal barrier permeability may lead to serious gastrointestinal (GI) disorders. LGS is caused by intestinal hyperpermeability due to changes in the expression levels and functioning of tight junctions. The influence of dietary habits on intestinal physiology is clearly visible in incidence rates of intestinal diseases in industrial and developing countries. Diseases which are linked to intestinal hyperpermeability tend to localize to Westernized countries, where a diet rich in fats and refined carbohydrates predominates. Several studies suggest that fructose is one of the key carbohydrates involved in the regulation of the intestinal permeability and its overuse may cause harmful effects, such as tight junction protein dysfunction. On the other hand, short chain fatty acids (mainly butyrate) at appropriate concentrations may lead to the reduction of intestinal permeability, which is beneficial in LGS. However, long chain fatty acids, including n-3 and n-6 polyunsaturated fatty acids have unclear properties. Some of those behave as components untightening and tightening the intestinal membrane.

Download Full-text

Yacon (Smallanthus sonchifolius): Effect on Integrity of Intestinal Barrier, Inflammatory Response and Oxidative Stress in Animal Model of Colon Cancer (P06-052-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-052-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Neuza Costa ◽

Thaisa Verediano ◽

Mirelle Viana ◽

Maria Vaz-Tostes

Keyword(s):

Oxidative Stress ◽

Colon Cancer ◽

Inflammatory Response ◽

Intestinal Permeability ◽

Immunoglobulin A ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Local Immunity ◽

Tnf Α ◽

And Oxidative Stress

Abstract Objectives To investigate the prebiotic effect of yacon, source of fructooligosaccharides (FOS), on the integrity of the intestinal barrier, inflammatory response and oxidative stress in rats with induced colon cancer. Methods 44 adult Wistar rats were distributed into 4 groups: S (without colon cancer and yacon; n = 10); C (with colon cancer without yacon; n = 12); Y (without colon cancer with yacon; n = 10); and CY (with colon cancer and yacon; n = 12). Animals of groups S and C received AIN-93 M diet and animals of groups Y and CY received the same diet but added with yacon flour containing 28.95% FOS, to provide 5% FOS in the diet, for 16 weeks. From week 4 to 8, the animals of C and CY groups received an intraperitoneal dose of 25 mg/kg body weight of 1.2-dimethylhydrazine (DMH-Sigma®) once a week. In the last week, 24h-urine collection was performed for intestinal permeability analysis using lactulose and mannitol. Blood sample was collected for the analysis of IL-10 and IL-12 cytokines (Milliplex® Map, Luminex®) and total antioxidant capacity - TAC (Elabscience®). Large intestine was collected for intraluminal pH, short chain fatty acids - SCFA (HPLC) and immunoglobulin A – sIgA (Cloud-Clone®) analysis. Normal distributed data were analyzed by Two-way ANOVA, followed by Newman-Keuls (p < 0.05), using GraphPad Prism®, version 7. Results Cancer-induced animals showed higher TNF-α, SCFA (acetate, propionate and butirate), and lower TAC. Yacon reduced intraluminal pH and lactulose/mannitol ratio, increased propionic acid in the feces, but showed no effect on IL-10, IL-12, TNF-α, and IL-10/IL-12 ratio. The levels of sIgA were increased only in the group fed yacon without cancer (group Y). Mannitol and TAC were higher in CY group, showing a significant interaction of yacon and colon cancer. Conclusions Yacon reduced pH, intestinal permeability and the oxidative stress associated with colon cancer. The local immunity (sIgA) was raised, although no effect was observed on cytokines with yacon consumption. Yacon is a rich source of FOS wich improves the intestinal barrier and mucosal immunity, particularly in healthy animals. Funding Sources CNPq, FAPES.

Download Full-text

A New Look at the Pathogenesis and Possibilities of Treatment and Prevention of Autoimmune Diseases with the Role of the Intestinal Barrier and Increased Intestinal Permeability

Effective Pharmacotherapy ◽

10.33978/2307-3586-2021-17-4-82-88 ◽

2021 ◽

Vol 17 (4) ◽

pp. 82-88

Author(s):

T.V. Kostoglod ◽

◽

T.S. Krolevets ◽

M.A. Livzan

Keyword(s):

Autoimmune Diseases ◽

Intestinal Permeability ◽

Lupus Erythematosus ◽

Intestinal Barrier ◽

Leaky Gut ◽

Treatment And Prevention ◽

Inflammatory Bowel ◽

The Relationship

We described components of the intestinal barrier that maintains to integrity and assess their contribution and development of leaky gut syndrome. The relationship between intestinal permeability syndrome and excessive bacterial translocation with autoimmune diseases such as celiac disease, inflammatory bowel disease, type 1 diabetes mellitus, autoimmune hepatitis, and systemic lupus erythematosus were analyzed. The reasons for the occurrence of this syndrome were considered, its importance in the occurrence of these diseases, as well as in the development of therapeutic and preventive measures, was determined.

Download Full-text

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Scientific Reports ◽

10.1038/s41598-020-75229-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tiberiu Loredan Stan ◽

Rana Soylu-Kucharz ◽

Stephen Burleigh ◽

Olena Prykhodko ◽

Ling Cao ◽

...

Keyword(s):

Mouse Model ◽

Tight Junction ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Intestinal Permeability ◽

Intestinal Barrier ◽

Systemic Circulation ◽

Intestinal Lumen ◽

Protein Levels ◽

Junction Proteins

Abstract Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

Download Full-text

Use of Short-Chain Fatty Acids for the Recovery of the Intestinal Epithelial Barrier Affected by Bacterial Toxins

Frontiers in Physiology ◽

10.3389/fphys.2021.650313 ◽

2021 ◽

Vol 12 ◽

Author(s):

Diliana Pérez-Reytor ◽

Carlos Puebla ◽

Eduardo Karahanian ◽

Katherine García

Keyword(s):

Fatty Acids ◽

Tight Junction ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Enteric Pathogens ◽

Short Chain ◽

Intestinal Lumen ◽

Barrier Integrity ◽

Intestinal Barrier Integrity ◽

Chain Fatty Acids

Short-chain fatty acids (SCFAs) are carboxylic acids produced as a result of gut microbial anaerobic fermentation. They activate signaling cascades, acting as ligands of G-protein-coupled receptors, such as GPR41, GPR43, and GPR109A, that can modulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction proteins functions. These junctions, located in the most apical zone of epithelial cells, control the diffusion of ions, macromolecules, and the entry of microorganisms from the intestinal lumen into the tissues. In this sense, several enteric pathogens secrete diverse toxins that interrupt tight junction impermeability, allowing them to invade the intestinal tissue and to favor gastrointestinal colonization. It has been recently demonstrated that SCFAs inhibit the virulence of different enteric pathogens and have protective effects against bacterial colonization. Here, we present an overview of SCFAs production by gut microbiota and their effects on the recovery of intestinal barrier integrity during infections by microorganisms that affect tight junctions. These properties make them excellent candidates in the treatment of infectious diseases that cause damage to the intestinal epithelium.

Download Full-text

Permeable gut syndrome, gluten, and autoimmune disease: an integrative review

International Journal of Nutrology ◽

10.54448/ijn2131 ◽

2021 ◽

Vol 14 (3) ◽

Author(s):

Etianne Andrade Araújo ◽

Alexandre Carli Pinto ◽

Danilo Everton Cunha Cavalcante ◽

Francione Moreira Cabral ◽

Jhonatas Mota Santos ◽

...

Keyword(s):

Autoimmune Diseases ◽

Intestinal Permeability ◽

Inflammatory Diseases ◽

Intestinal Wall ◽

The Body ◽

Food Allergies ◽

Leaky Gut ◽

Basic Functions ◽

To Come

Introduction: Leaky Bowel Syndrome or intestinal permeability is a gastrointestinal condition that affects many people. A leaky gut is a trigger for many changes like food allergies and intolerances, autoimmune diseases, colitis, Crohn's and celiac disease, inflammatory diseases, depression, insulin resistance and even cancer have been linked. Objective: To analyze basic information for a better understanding of this topic, from the functioning of the gastrointestinal tract, as the diseases that are associated with it, how the immune system responds to these injuries, the quality, and importance of proteins, and the consequence of this disorder to the body human. Methods: Conducted an integrative literature review. The Pubmed, Google Scholar, and Scielo databases were consulted. Results: The intestine is naturally permeable to many small molecules, so it can absorb vital nutrients. Regulating intestinal permeability is one of the most basic functions of the cells that make up the intestinal wall. But one factor calls our attention, what is the role of gluten in the development of this disease and the worsening of symptoms? Insensitive people, gluten can cause cells to release zonulin, a protein that can break the tight junctions of intestinal tissue. Other factors—such as infections, toxins, stress, and age—can also cause these joints to come apart. Once strong joints break, you have a leaky gut. Gluten, therefore, is the number one cause of this process. A person with a leaky intestine tends to be highly allergic and intolerant to foods and substances, and may or may not manifest intestinal discomfort such as gas and bloating. Conclusion: Based on the literature that supports this theme, it is considered that gluten is a possible villain in the intestinal tract and is related to many autoimmune diseases. Furthermore, as an interventional measure, it is necessary to reduce some carbohydrate-rich foods and the maintenance of the body's balance with specific diets and physical activities.

Download Full-text

Diurnal variations in intestinal barrier integrity and liver pathology in mice: implications for alcohol binge

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00103.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. G131-G141 ◽

Cited By ~ 8

Author(s):

Robin M. Voigt ◽

Christopher B. Forsyth ◽

Maliha Shaikh ◽

Lijuan Zhang ◽

Shohreh Raeisi ◽

...

Keyword(s):

Liver Injury ◽

Intestinal Permeability ◽

Intestinal Barrier ◽

Time Of Day ◽

Chow Diet ◽

Barrier Dysfunction ◽

Barrier Integrity ◽

Intestinal Barrier Dysfunction ◽

Daily Variations ◽

Intestinal Barrier Integrity

Recent studies suggest that circadian rhythms regulate intestinal barrier integrity, but it is not clear whether there are daily variations in barrier integrity. This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. C57BL6/J male mice were fed a standard chow diet, an alcohol-containing liquid diet, or an alcohol control diet for 4 wk. During week 5 (i.e., on days 43–45), mice received three once-daily gavages of alcohol (6 g/kg) or the control (phosphate-buffered saline) at the same time each day. Immediately after the binge on the second day, intestinal permeability was assessed. Four hours after the third and final binge, mice were euthanized and tissue samples collected. The results demonstrated diet-specific and outcome-specific effects of time, alcohol, and/or time by alcohol interaction. Specifically, the alcohol binge robustly influenced markers of intestinal barrier integrity, and liver markers were robustly influenced by time of day. Only intestinal permeability (i.e., sucralose) demonstrated a significant effect of time and also showed a binge by time interaction, suggesting that the time of the alcohol binge influences colonic permeability. NEW & NOTEWORTHY This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. We conclude that 1) alcohol binge significantly impacted markers of intestinal permeability, 2) time of day significantly affected liver outcomes, and 3) the time of day influenced colonic permeability.

Download Full-text

Crosstalks between helminthes and microbiota to improve gut health

QJM ◽

10.1093/qjmed/hcaa060.007 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

H S Elwakil

Keyword(s):

Immune System ◽

Intestinal Tract ◽

Inflammatory Diseases ◽

Short Chain Fatty Acids ◽

Mammalian Host ◽

Host Immune System ◽

Helminth Parasites ◽

Gut Health ◽

Intestinal Microbes ◽

Inflammatory Bowel

Abstract Intestinal helminths are potent regulators of their host’s immune system and can protect against Inflammatory bowel disease. This anti-inflammatory activity remains largely unknown. Is it purely intrinsic to helminths, or whether it also involved cross interaction with the local microbiota? Microbiota and helminths have coevolved within the mammalian host. Both have common strategies of establishing a new homeostasis in the host intestinal tract. These strategies include regulating host immunity to permit their survival through the induction of suppressive regulatory T cells ( Tregs ). Also, Short-Chain Fatty Acids (SCFAs) may be a possible another common pathway shared by microbiota and helminths. SCFAs are microbial metabolite that are derived from microbial fermentation of dietary fibers in the colon. Similarly, some helminth infection leads to SCFAs elevation in human. SCFAs can potentiate T regs generation and IL- 10 production in the periphery. Dissecting the multidirectional interactions among intestinal microbes, helminth parasites and their host immune system will hopefully enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases

Download Full-text

Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review

Advances in Nutrition ◽

10.1093/advances/nmz061 ◽

2019 ◽

Cited By ~ 24

Author(s):

Michael W Rohr ◽

Chandrakala A Narasimhulu ◽

Trina A Rudeski-Rohr ◽

Sampath Parthasarathy

Keyword(s):

Intestinal Permeability ◽

High Fat Diet ◽

Intestinal Tract ◽

Intestinal Barrier ◽

Interferon Γ ◽

Current Data ◽

Dietary Fats ◽

High Fat ◽

Negative Effects ◽

Intestinal Mucus

ABSTRACT The intestinal tract is the largest barrier between a person and the environment. In this role, the intestinal tract is responsible not only for absorbing essential dietary nutrients, but also for protecting the host from a variety of ingested toxins and microbes. The intestinal barrier system is composed of a mucus layer, intestinal epithelial cells (IECs), tight junctions (TJs), immune cells, and a gut microbiota, which are all susceptible to external factors such as dietary fats. When components of this barrier system are disrupted, intestinal permeability to luminal contents increases, which is implicated in intestinal pathologies such as inflammatory bowel disease, necrotizing enterocolitis, and celiac disease. Currently, there is mounting evidence that consumption of excess dietary fats can enhance intestinal permeability differentially. For example, dietary fat modulates the expression and distribution of TJs, stimulates a shift to barrier-disrupting hydrophobic bile acids, and even induces IEC oxidative stress and apoptosis. In addition, a high-fat diet (HFD) enhances intestinal permeability directly by stimulating proinflammatory signaling cascades and indirectly via increasing barrier-disrupting cytokines [TNFα, interleukin (IL) 1B, IL6, and interferon γ (IFNγ)] and decreasing barrier-forming cytokines (IL10, IL17, and IL22). Finally, an HFD negatively modulates the intestinal mucus composition and enriches the gut microflora with barrier-disrupting species. Although further research is necessary to understand the precise role HFDs play in intestinal permeability, current data suggest a stronger link between diet and intestinal disease than was first thought to exist. Therefore, this review seeks to highlight the various ways an HFD disrupts the gut barrier system and its many implications in human health.

Download Full-text