Methods to Strengthen Gut Barrier Function with Probiotics

The intestinal barrier, an indispensable guardian of gastrointestinal health, mediates the intricate exchange between internal and external environments. Anchored by evolutionarily conserved junctional complexes, this barrier meticulously regulates paracellular permeability in essentially all living organisms. Disruptions in intestinal junctional complexes, prevalent in inflammatory bowel diseases and irritable bowel syndrome, compromise barrier integrity and often lead to the notorious "leaky gut" syndrome. Critical to the maintenance of the intestinal barrier is a finely orchestrated network of intrinsic and extrinsic factors that modulate the expression, composition, and functionality of junctional complexes. This review navigates through the composition of key junctional complex components and the common methods used to assess intestinal permeability. It also explores the critical intracellular signaling pathways that modulate these junctional components. Lastly, we delve into the complex dynamics between the junctional complexes, microbial communities, and environmental chemical... Read More

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Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota.

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Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the “gut-organ” axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as “detecting agents” for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may a... Read More

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Abstract Nowadays, a pathological increase in the permeability of the intestinal barrier (the so-called leaky gut) is increasingly being diagnosed. This condition can be caused by various factors, mainly from the external environment. Damage to the intestinal barrier entails a number of adverse phenomena: dysbiosis, translocation of microorganisms deep into the intestinal tissue, immune response, development of chronic inflammation. These phenomena can ultimately lead to a vicious cycle that promotes the development of inflammation and further damage to the barrier. Activated immune cells in mucosal tissues with broken barriers can migrate to other organs and negatively affect their functioning. Damaged intestinal barrier can facilitate the development of local diseases such as irritable bowel disease, inflammatory bowel disease or celiac disease, but also the development of systemic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, hepatitis, and lupus erythematosus, neurodegenerative or psychiatric conditions, or metabolic diseases such as diabetes or obes... Read More

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The intestinal barrier plays a crucial role in homeostasis, both by facilitating absorption of nutrients and fluids, and providing a tight shield to prevent the invasion by either pathogen or commensal microorganisms. Intestinal barrier malfunction is associated with systemic inflammation, oxidative stress, and decreased insulin sensitivity, which may lead to the dysregulation of other tissues. Therefore, a deeper understanding of physiological aspects related to an enhanced barrier function is of significant scientific and clinical relevance. The naked mole-rat has many unusual biological features, including attenuated colonic neuron sensitivity to acid and bradykinin, and resistance to chemical-induced intestinal damage. However, insight into their intestinal barrier physiology is scarce. Here, we observed notable macroscopic and microscopic differences in intestinal tissue structure between naked mole-rats and mice. Moreover, naked mole-rats showed increased number of larger goblet cells and elevated mucus content. In measuring gut permeability, naked mole-rats showed reduced perm... Read More

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Gut epithelial barrier perturbation leads to leaky gut syndrome and permeation of substances activating immune response. Polyphenols can improve intestinal barrier function and represent candidates for preventing development of leaky gut. Herein, we evaluated

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The gut barrier is a sophisticated and dynamic system that forms the frontline defense between the external environment and the body's internal milieu and includes various structural and functional components engaged not only in digestion and nutrient absorption but also in immune regulation and overall health maintenance.

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Editorial: The role of physical and biological gut barriers in modulating crosstalk between the microbiota and the immune system

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The intestinal wall is a selectively permeable barrier between the content of the intestinal lumen and the internal environment of the body. Disturbances of intestinal wall permeability can potentially lead to unwanted activation of the enteric immune system due to excessive contact with gut microbiota and its components, and the development of endotoxemia, when the level of bacterial lipopolysaccharides increases in the blood, causing chronic low-intensity inflammation. In this review, the following aspects are covered: the structure of the intestinal wall barrier; the influence of the gut microbiota on the permeability of the intestinal wall via the regulation of functioning of tight junction proteins, synthesis/degradation of mucus and antioxidant effects; the molecular mechanisms of activation of the pro-inflammatory response caused by bacterial invasion through the TLR4-induced TIRAP/MyD88 and TRAM/TRIF signaling cascades; the influence of nutrition on intestinal permeability, and the influence of exercise with an emphasis on exercise-induced heat stress and hypoxia. Overall, th... Read More

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As a unique microenvironment, the gastro-intestinal tract (GIT) is one of the most important ecosystems that have a vital role in human health. The main components of the defense mechanisms required to avoid infection and inflammation due to pathogenic bacteria penetration are barrier functions in the intestinal epithelium and mucosal immune cells. Probiotics can increase the integrity of the epithelial lining and induce tight connections among epithelial cells forming a functional barrier. They can reinforce this barrier through increasing mucins, tight junction protein expression and localization, and increase the goblet and Paneth cells. Also, probiotics increase intestinal epithelial barrier function by producing cytoprotective substances and inhibiting epithelial damage caused by cytokines and oxidants improving cell viability. Some important mechanisms underlying the actions of probiotics include modulating the microbiota of the gut, binding to adhesion sites of epithelial surfaces and competitive exclusion of pathogens, immunomodulation, epithelial obstruction, and regulating ... Read More

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The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or “leaky gut”, has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes.

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The intestinal mucosal barrier plays a critical role in maintaining the integrity of the gastrointestinal (GI) tract and protecting the body from harmful toxins and pathogens. Nutrition additionally serves as a vital component in maintaining bodily homeostasis. Macronutrients, micronutrients, and specific dietary habits exert profound effects on the immune system. The complex interactions of the immune system reflect a multifaceted, integrated epithelial and immune cell-mediated regulatory system. While several factors can influence the intestinal mucosal barrier and its pro- and anti-inflammatory processes, such as myeloid cell, regulatory T cell (Treg), or intraepithelial lymphocyte populations, there is growing evidence that macronutrients play an essential role in regulating its function. Herein this is a review of the peer-reviewed literature pertaining to dietary effects on mucosal integrity, including intraepithelial lymphocyte populations and immune function. This review is intended to explore the underlying mechanisms by which macronutrients impact and modulate the mucosal i... Read More

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The maintenance of the intestinal barrier is crucial for the overall balance of the gut and the organism. Dysfunction of the intestinal barrier is closely associated with intestinal diseases. In recent years, due to the increased presence of nanoparticles (NPs) in the human diet, there has been a growing concern regarding the safety and potential impact of these NPs on gastrointestinal health. The interactions between food-derived NPs and the intestinal barrier are numerous. This review provides an introduction to the structure and function of the intestinal barrier along with a comprehensive summary of the interactions between food NPs and the intestinal barrier. Additionally, we highlight the potential connection between the food NPs-induced dysfunction of the intestinal barrier and inflammatory bowel disease. Finally, we discuss the enhancement of food NPs on the repair of the intestinal barrier damage and the nutrients absorption. This review holds significant importance in furthering our understanding of the regulatory mechanisms of food-derived NPs on the intestinal barrier.

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The topic of increased intestinal permeability is associated with disruption of the intestinal barrier, leading to the "leaky gut" syndrome. Depressive disorders often coexist with abdominal obesity, metabolic syndrome, or its components and complications. Intestinal permeability has been proven to relate to all of the above.

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Abstract The intestinal barrier is mainly formed by a monolayer of epithelial cells, which forms a physical barrier to protect the gut tissues from external insults and provides a microenvironment for commensal bacteria to colonize while ensuring immune tolerance. Moreover, various immune cells are known to significantly contribute to intestinal barrier function by either directly interacting with epithelial cells or by producing immune mediators. Fulfilling this function of the gut barrier for mucosal homeostasis requires not only the intrinsic regulation of intestinal epithelial cells (IECs) but also constant communication with immune cells and gut microbes. The reciprocal interactions between IECs and immune cells modulate mucosal barrier integrity. Dysregulation of barrier function could lead to dysbiosis, inflammation, and tumorigenesis. In this overview, we provide an update on the characteristics and functions of IECs, and how they integrate their functions with tissue immune cells and gut microbiota to establish gut homeostasis.

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Accumulating evidence emphasizes the critical reciprocity between gut microbiota and intestinal barrier function in maintaining the gastrointestinal homeostasis. Given the fundamental role caused by intestinal permeability, which has been scrutinized as a measurable potential indicator of perturbed barrier function in clinical researches, it seems not surprising that recent decades have been marked by augmented efforts to determine the interaction between intestinal microbes and permeability of the individual. However, despite the significant progress in characterizing intestinal permeability and the commensal bacteria in the intestine, the mechanisms involved are still far from being thoroughly revealed. In the present review, based on multiomic methods, high-throughput sequencing and molecular biology techniques, the impacts of gut microbiota on intestinal permeability as well as their complex interaction networks are systematically summarized. Furthermore, the diseases related to intestinal permeability and main causes of changes in intestinal permeability are briefly introduced. ... Read More

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Intestinal permeability is a critical component of gut barrier function. Barrier dysfunction can be triggered by certain stressors such as exercise, and if left unmanaged can lead to local and systemic disorders. The aim of this study was to investigate the effects of a specific whey protein fraction in alleviating exercise-induced gut permeability as assessed by recovery of lactulose/rhamnose (L/R) and lactulose/mannitol (L/M) urinary probes.

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The intestinal epithelium not only facilitates the absorption of nutrients, but also plays a pivotal role in guarding intestinal homeostasis and preventing opportunistic gut microbiome invasions. The intestinal epithelial cells have diverse and coordinated regulatory networks that provide intricate lines of defense, in order to maintain the integrity of the intestinal barrier. The epithelial defense comprises the anatomical structure of intestinal epithelial cells as a stout physical barrier and its covering mucus layer containing diverse antimicrobial peptides. In addition, epithelial cells are well-equipped with diverse microbial sensors, which upon activation induce the expression of downstream immunomodulatory networks of cytokines and chemokines. In this review, we summarize the intestinal epithelial cells’ defense mechanisms and their role in maintaining intestinal homeostasis.

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The intestinal mucus barrier is an important line of defense against gut pathogens. Damage to this barrier brings bacteria into close contact with the epithelium, leading to intestinal inflammation. Therefore, its restoration is a promising strategy for alleviating intestinal inflammation. This study showed that

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Fx effectively prevents LPS-induced intestinal barrier injury via inhibiting intestinal inflammation and oxidative stress.

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