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Journal ArticleDOI

Modulation of intestinal barrier by intestinal microbiota: pathological and therapeutic implications.

01 Mar 2013-Pharmacological Research (Pharmacol Res)-Vol. 69, Iss: 1, pp 42-51
TL;DR: A better understanding of the role of the intestinal microbiota in maintaining a functional intestinal barrier may help develop targeted strategies to prevent and treat disease.
About: This article is published in Pharmacological Research.The article was published on 2013-03-01. It has received 331 citations till now. The article focuses on the topics: Dysbiosis & Gut flora.
Citations
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Journal ArticleDOI
TL;DR: This review summarises the current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions.
Abstract: The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease Multiple factors contribute to the establishment of the human gut microbiota during infancy Diet is considered as one of the main drivers in shaping the gut microbiota across the life time Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions

1,708 citations

Journal ArticleDOI
TL;DR: In this paper, the authors proposed the intestinal-microbiota-liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease.
Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of worldwide cancer mortality. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Increasing evidence points towards a key role of the bacterial microbiome in promoting the progression of liver disease and the development of HCC. Here, we will review mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on the leaky gut, bacterial dysbiosis, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. On the basis of accumulating evidence from preclinical studies, we propose the intestinal-microbiota-liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We will review in detail therapeutic modalities and discuss clinical settings in which targeting the gut-microbiota-liver axis for the prevention of disease progression and HCC development seems promising.

343 citations

Journal ArticleDOI
TL;DR: This review examines the fundamentals of neurogastroenterology that may underlie the pathophysiology of functional GI disorders (FGIDs) and emphasizes recent advances in understanding of the enteric nervous system, sensory physiology underlying pain, and stress signaling pathways.

315 citations


Cites methods from "Modulation of intestinal barrier by..."

  • ...Adapted with permission from Natividad et al.(46) MAMP, microbeassociated molecular pattern; PRR, pattern recognition receptors....

    [...]

Journal ArticleDOI
TL;DR: A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of Gut microbiota is warranted for a better management of ASD and mood disorders.
Abstract: The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.

284 citations

Journal ArticleDOI
TL;DR: According to this hypothesis, inflammatory bowel disease may be both precipitated and treated by either stimulation or downregulation of the different elements of the mucosal barrier, with the outcome depending on timing, the cell type affected, and other factors.
Abstract: Intestinal mucosal barrier function is the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules while preserving the ability to absorb nutrients. The central element is the epithelial layer, which physically separates the lumen and the internal milieu and is in charge of vectorial transport of ions, nutrients, and other substances. The secretion of mucus-forming mucins, sIgA, and antimicrobial peptides reinforces the mucosal barrier on the extraepithelial side, while a variety of immune cells contributes to mucosal defense in the inner side. Thus, the mucosal barrier is of physical, biochemical, and immune nature. In addition, the microbiota may be viewed as part of this system because of the mutual influence occurring between the host and the luminal microorganisms. Alteration of the mucosal barrier function with accompanying increased permeability and/or bacterial translocation has been linked with a variety of conditions, including inflammatory bowel disease. Genetic and environmental factors may converge to evoke a defective function of the barrier, which in turn may lead to overt inflammation of the intestine as a result of an exacerbated immune reaction toward the microbiota. According to this hypothesis, inflammatory bowel disease may be both precipitated and treated by either stimulation or downregulation of the different elements of the mucosal barrier, with the outcome depending on timing, the cell type affected, and other factors. In this review, we cover briefly the elements of the barrier and their involvement in functional defects and the resulting phenotype.

268 citations


Cites background from "Modulation of intestinal barrier by..."

  • ...bowel syndrome, metabolic syndrome, allergy, hepatic inflammation, septic shock, etc.(2) IBD comprises ulcerative colitis (UC)...

    [...]

References
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Journal ArticleDOI
22 Oct 1993-Cell
TL;DR: The results indicate that the bowel inflammation in the mutants originates from uncontrolled immune responses stimulated by enteric antigens and that IL-10 is an essential immunoregulator in the intestinal tract.

4,196 citations

Journal ArticleDOI
23 Jul 2004-Cell
TL;DR: It is shown that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis and protection from injury.

3,972 citations

Journal ArticleDOI
TL;DR: The results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment and exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 production.
Abstract: A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-kappaB activity, F. prausnitzii had no effect on IL-1beta-induced NF-kappaB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-gamma production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-kappaB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment.

3,653 citations

Journal ArticleDOI
TL;DR: Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli, along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.
Abstract: Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens and microbial products. Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli. Here I discuss these discoveries along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.

2,795 citations

Journal ArticleDOI
TL;DR: A microarray is designed to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria and suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby.
Abstract: Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward systematically investigating these questions, we designed a microarray to detect and quantitate the small subunit ribosomal RNA (SSU rRNA) gene sequences of most currently recognized species and taxonomic groups of bacteria. We used this microarray, along with sequencing of cloned libraries of PCR-amplified SSU rDNA, to profile the microbial communities in an average of 26 stool samples each from 14 healthy, full-term human infants, including a pair of dizygotic twins, beginning with the first stool after birth and continuing at defined intervals throughout the first year of life. To investigate possible origins of the infant microbiota, we also profiled vaginal and milk samples from most of the mothers, and stool samples from all of the mothers, most of the fathers, and two siblings. The composition and temporal patterns of the microbial communities varied widely from baby to baby. Despite considerable temporal variation, the distinct features of each baby's microbial community were recognizable for intervals of weeks to months. The strikingly parallel temporal patterns of the twins suggested that incidental environmental exposures play a major role in determining the distinctive characteristics of the microbial community in each baby. By the end of the first year of life, the idiosyncratic microbial ecosystems in each baby, although still distinct, had converged toward a profile characteristic of the adult gastrointestinal tract.

2,632 citations

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