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 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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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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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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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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Intestinal barrier integrity is essential in order to maintain the homeostasis of mucosal functions and efficient defensive reactions against chemical and microbial challenges. An impairment of the intestinal barrier has been observed in several chronic diseases. The gut microbiota and its impact on intestinal homeostasis is well described and numerous studies suggest the ability of some probiotic strains to protect the intestinal epithelial integrity and host homeostasis. In this work, we aimed to assess the beneficial effects of three Lactobacillus strains (Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC03, and Lactiplantibacillus plantarum CNCM I-4459) and their mechanism of action in low-grade inflammation or neonatal maternal separation models in mice. We compared the impact of these strains to that of the well-known probiotic Lacticaseibacillus rhamnosus GG. Our results demonstrated that the three strains have the potential to restore the barrier functions by (i) increasing mucus production, (ii) restoring normal permeability, and (iii) modulating colonic hyperse... Read More

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The intestinal barrier orchestrates selective permeability to nutrients and metabolites while excluding noxious stimuli. Recent scientific advances establishing a causal role for the gut microbiota in human health outcomes have generated a resurgent interest toward intestinal permeability. Considering the well-established role of the gut barrier in protection against foreign antigens, there is mounting evidence for a causal link between gut permeability and the microbiome in regulating human health. However, an understanding of the dynamic hostmicrobiota interactions that govern intestinal barrier functions remains poorly defined. Furthermore, the system-level mechanisms by which microbiome-targeted therapies, such as probiotics and prebiotics, simultaneously promote intestinal barrier function and host health remain an area of active investigation. This review summarizes the recent advances in understanding the dynamics of intestinal permeability in human health and its integration with gut microbiota. We further summarize mechanisms by which probiotics/prebiotics influence the gut... Read More

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Intestinal epithelium functions as a tissue barrier to prevent interaction between the internal compartment and the external milieu. Intestinal barrier function also determines epithelial polarity for the absorption of nutrients and the secretion of waste products. These vital functions require strong integrity of tight junction proteins. In fact, intestinal tight junctions that seal the paracellular space can restrict mucosal-to-serosal transport of hostile luminal contents. Tight junctions can form both an absolute barrier and a paracellular ion channel. Although defective tight junctions potentially lead to compromised intestinal barrier and the development and progression of gastrointestinal (GI) diseases, no FDA-approved therapies that recover the epithelial tight junction barrier are currently available in clinical practice. Here, we discuss the impacts and regulatory mechanisms of tight junction disruption in the gut and related diseases. We also provide an overview of potential therapeutic targets to restore the epithelial tight junction barrier in the GI tract.

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Physiologically, the intestinal barrier plays a crucial role in homeostasis and nutrient absorption and prevents pathogenic entry, harmful metabolites, and endotoxin absorption. Recent advances have highlighted the association between severely damaged intestinal barriers and diabetes, obesity, fatty liver, and cardiovascular diseases. Evidence indicates that an abated intestinal barrier leads to endotoxemia associated with systemic inflammation, insulin resistance, diabetes, and lipid accumulation, accelerating obesity and fatty liver diseases. Nonetheless, the specific mechanism of intestinal barrier damage and the effective improvement of the intestinal barrier remain to be explored. Here, we discuss the crosstalk between changes in the intestinal barrier and metabolic disease. This paper also highlights how to improve the gut barrier from the perspective of natural medicine, gut microbiota remodeling, lifestyle interventions, and bariatric surgery. Finally, potential challenges and prospects for the regulation of the gut barrier-metabolic disease axis are discussed, which may prov... Read More

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Dysfunction of gut barrier is known as "leaky gut" or increased intestinal permeability. Numerous recent scientific evidences showed the association between gut dysfunction and multiple gastrointestinal tract (GI) and non-GI diseases. Research also demonstrated that food plays a crucial role to cause or remedy gut dysfunction related to diseases. We reviewed recent articles from electronic databases, mainly PubMed. The data were based on animal models, cell models, and human research in vivo and in vitro models. In this comprehensive review, our aim focused on the relationship between dietary factors, intestinal permeability dysfunction, and related diseases. This review synthesizes currently available literature and is discussed in three parts: (a) the mechanism of gut barrier and function, (b) food and dietary supplements that may promote gut health, and food or medication that may alter gut function, and (c) a table that organizes the synthesized information by general mechanisms for diseases related to leaky gut/intestinal permeability and associated dietary influences. With futu... Read More

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Studies have shown that the various parts of intestinal barrier can synergistically defend against pathogens in multiple ways.

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CA supplementation could enhance intestinal integrity and barrier function by modifying intestinal microbiota and its metabolites, which could lead to a reduction in inflammatory responses and oxidative stress in LPS-challenged piglets.

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The intestinal barrier dysfunction is intimately associated with inflammatory bowel diseases (IBD) as the gut barrier provides the first line of protection to host from external factors. The pathogenesis of IBD is multifactorial resulting from combinations of genetic polymorphism, environmental factors, diet, altered microbiota and the immune system. Aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor which upon activation can regulate many pathophysiological functions like inflammation and gut barrier homeostasis. Recently, we identified that microbial metabolite Urolithin A (UroA) mitigated colitis in pre-clinical models through activation of AhR-dependent pathways at two distinct levels by preserving the gut barrier function and reducing systemic and acute inflammation. However, the interplay between the enhanced barrier function and reduction in inflammation and the requirement of specific cell types to mediate the UroA activities remains to be established. In the current study, we evaluated the UroA mediated cell specific requirement... Read More

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The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and ... Read More

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The intestinal barrier is a physiological functional unit that separates the intestinal lumen from the inner environment of the body. Certain food ingredients or the lack of it, infective stress, and microbial dysbiosis may predispose to the development of intestinal permeability (IP) or a leaky gut. This may further provide access to a host of antigens of varied origins that may stimulate an immune response and translocation of reactivated T-cells to develop allergic inflammation in lungs and skin. Several laboratory tests are available to objectively assess the IP, notably being the lactulose:mannitol test. Although various therapeutic agents including dietary constituents have been claimed to reverse the IP and allergic manifestations, their impact remains to be proven conclusively.

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The intestinal barrier is a structure that prevents harmful substances, such as bacteria and endotoxins, from penetrating the intestinal wall and entering human tissues, organs, and microcirculation. It can separate colonizing microbes from systemic tissues and prevent the invasion of pathogenic bacteria. Pathological conditions such as shock, trauma, stress, and inflammation damage the intestinal barrier to varying degrees, aggravating the primary disease. Intestinal probiotics are a type of active microorganisms beneficial to the health of the host and an essential element of human health. Reportedly, intestinal probiotics can affect the renewal of intestinal epithelial cells, and also make cell connections closer, increase the production of tight junction proteins and mucins, promote the development of the immune system, regulate the release of intestinal antimicrobial peptides, compete with pathogenic bacteria for nutrients and living space, and interact with the host and intestinal commensal flora to restore the intestinal barrier. In this review, we provide a comprehensive over... Read More

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