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Digestive and Liver Disease : Official... Mar 2020Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other... (Review)
Review
Short bowel syndrome (SBS) is a rare malabsorptive disorder as a result of the loss of bowel mass mostly secondary to surgical resection of the small intestine. Other causes are vascular diseases, neoplasms or inflammatory bowel disease. The spectrum of the disease is widely variable from single micronutrient malabsorption to complete intestinal failure, depending on the remaining length of the small intestine, the anatomical portion of intestine and the function of the remnant bowel. Over the last years, the management of affected patients has remarkably improved with the increase in patients' quality of life and survival, mainly thanks to advances in home-based parenteral nutrition (PN). In the last ten years new treatment strategies have become available together with increasing experience and the encouraging results with new drugs, such as teduglutide, have added a new dimension to the management of SBS. This review aims to summarize the knowledge available in the current literature on SBS epidemiology, pathophysiology, and its surgical (including intestinal lengthening procedures and intestinal transplantation) and medical management with emphasis on the recent advances. Moreover, this review attempts to provide the new understanding and recent approaches to SBS complications such as sepsis, catheter thrombosis, and intestinal failure-associated liver disease.
Topics: Disease Management; Gastrointestinal Agents; Humans; Intestines; Parenteral Nutrition, Home; Peptides; Quality of Life; Short Bowel Syndrome
PubMed: 31892505
DOI: 10.1016/j.dld.2019.11.013 -
Trends in Pharmacological Sciences Nov 2020Metformin can improve patients' hyperglycemia through significant suppression of hepatic glucose production. However, up to 300 times higher concentrations of metformin... (Review)
Review
Metformin can improve patients' hyperglycemia through significant suppression of hepatic glucose production. However, up to 300 times higher concentrations of metformin accumulate in the intestine than in the circulation, where it alters nutrient metabolism in intestinal epithelial cells and microbiome, leading to increased lactate production. Hepatocytes use lactate to make glucose at the cost of energy expenditure, creating a futile intestine-liver cycle. Furthermore, metformin reduces blood lipopolysaccharides and its initiated low-grade inflammation and increased oxidative phosphorylation in liver and adipose tissues. These metformin effects result in the improvement of insulin sensitivity and glucose utilization in extrahepatic tissues. In this review, I discuss the current understanding of the impact of metformin on systemic metabolism and its molecular mechanisms of action in various tissues.
Topics: Animals; Glucose; Glycolysis; Humans; Hyperglycemia; Intestinal Mucosa; Intestines; Lipid Metabolism; Liver; Metabolism; Metformin; Microbiota
PubMed: 32994049
DOI: 10.1016/j.tips.2020.09.001 -
Frontiers in Immunology 2018Macrophages are increasingly recognized as essential players in the maintenance of intestinal homeostasis and as key sentinels of the intestinal immune system. However,... (Review)
Review
Macrophages are increasingly recognized as essential players in the maintenance of intestinal homeostasis and as key sentinels of the intestinal immune system. However, somewhat paradoxically, they are also implicated in chronic pathologies of the gastrointestinal tract, such as inflammatory bowel disease (IBD) and are therefore considered potential targets for novel therapies. In this review, we will discuss recent advances in our understanding of intestinal macrophage heterogeneity, their ontogeny and the potential factors that regulate their origin. We will describe how the local environment of the intestine imprints the phenotypic and functional identity of the macrophage compartment, and how this changes during intestinal inflammation and infection. Finally, we highlight key outstanding questions that should be the focus of future research.
Topics: Animals; Cell Differentiation; Homeostasis; Humans; Inflammatory Bowel Diseases; Intestines; Macrophages
PubMed: 30538701
DOI: 10.3389/fimmu.2018.02733 -
Frontiers in Immunology 2021In inflammatory bowel disease (IBD), intestinal mucosa cell and intestinal epithelial cell are severely damaged, and then their susceptibility to bacteria increases, so... (Review)
Review
In inflammatory bowel disease (IBD), intestinal mucosa cell and intestinal epithelial cell are severely damaged, and then their susceptibility to bacteria increases, so many commensal bacteria become pathogenic. The pathogenic commensal bacteria can stimulate a series of compensatory immune responses in the intestine. However, the immune response prevents the intestinal tract from restoring homeostasis, which in turn produces an indispensable inflammatory response. On the contrary, in IBD, the fierce inflammatory response contributes to the development of IBD. However, the effect of commensal bacteria on inflammation in IBD has not been clearly studied. Therefore, we further summarize the changes brought about by the changes of commensal bacteria to the inflammation of the intestines and their mutual influence. This article reviews the protective mechanism of commensal bacteria in healthy people and the mechanism of commensal bacteria and immune response to the destruction of the intestinal barrier when IBD occurs. The treatment and prevention of IBD are also briefly summarized.
Topics: Bacteria; Cytokines; Homeostasis; Humans; Immunity, Innate; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Models, Immunological; Symbiosis; Virulence
PubMed: 34858414
DOI: 10.3389/fimmu.2021.761981 -
Revista Espanola de Enfermedades... Nov 2015The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and... (Review)
Review
The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.
Topics: Animals; Digestive System Diseases; Humans; Intestinal Mucosa; Intestines; Tight Junctions
PubMed: 26541659
DOI: 10.17235/reed.2015.3846/2015 -
American Journal of Transplantation :... Jan 2016Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral...
Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Graft Survival; Humans; Immunosuppressive Agents; Intestinal Diseases; Intestines; Liver Transplantation; Male; Middle Aged; Prevalence; Tissue Donors; Treatment Outcome; United States; Waiting Lists; Young Adult
PubMed: 26755265
DOI: 10.1111/ajt.13669 -
Biophysical Journal Feb 2021In the intestinal epithelium, proliferated epithelial cells ascend the crypts and villi and shed at the villus tips into the gut lumen. In this study, we theoretically...
In the intestinal epithelium, proliferated epithelial cells ascend the crypts and villi and shed at the villus tips into the gut lumen. In this study, we theoretically investigate the roles of the villi on cell turnover. We present a stochastic model that focuses on the duration over which cells migrate the shortest paths between the crypt orifices and the villus tips, where shedding cells are randomly chosen from among those older than the shortest-path cell migration times. By extending the length of the shortest path to delay cell shedding, the finger-like shape of the villus would tightly regulate shedding-cell ages compared with flat surfaces and shorter projections; the villus allows epithelial cells to shed at around the same age, which limits them from shedding early or staying in the epithelium for long periods. Computational simulations of cell dynamics agreed well with the predictions. We also examine various mechanical conditions of cells and confirm that coordinated collective cell migration supports the predictions. These results suggest the important roles of the villi in homeostatic maintenance of the small intestine, and we discuss the applicability of our approach to other tissues with collective cell movement.
Topics: Epithelial Cells; Epithelium; Intestinal Mucosa; Intestine, Small; Intestines
PubMed: 33453270
DOI: 10.1016/j.bpj.2021.01.003 -
Nature Oct 2020The coevolution of mammalian hosts and their beneficial commensal microbes has led to development of symbiotic host-microbiota relationships. Epigenetic machinery...
The coevolution of mammalian hosts and their beneficial commensal microbes has led to development of symbiotic host-microbiota relationships. Epigenetic machinery permits mammalian cells to integrate environmental signals; however, how these pathways are fine-tuned by diverse cues from commensal bacteria is not well understood. Here we reveal a highly selective pathway through which microbiota-derived inositol phosphate regulates histone deacetylase 3 (HDAC3) activity in the intestine. Despite the abundant presence of HDAC inhibitors such as butyrate in the intestine, we found that HDAC3 activity was sharply increased in intestinal epithelial cells of microbiota-replete mice compared with germ-free mice. This divergence was reconciled by the finding that commensal bacteria, including Escherichia coli, stimulated HDAC activity through metabolism of phytate and production of inositol-1,4,5-trisphosphate (InsP). Both intestinal exposure to InsP and phytate ingestion promoted recovery following intestinal damage. Of note, InsP also induced growth of intestinal organoids derived from human tissue, stimulated HDAC3-dependent proliferation and countered butyrate inhibition of colonic growth. Collectively, these results show that InsP is a microbiota-derived metabolite that activates a mammalian histone deacetylase to promote epithelial repair. Thus, HDAC3 represents a convergent epigenetic sensor of distinct metabolites that calibrates host responses to diverse microbial signals.
Topics: Animals; Gastrointestinal Microbiome; Histone Deacetylases; Humans; Inositol 1,4,5-Trisphosphate; Intestinal Mucosa; Intestines; Mice; Mice, Inbred C57BL; Organoids; Phytic Acid; Symbiosis
PubMed: 32731255
DOI: 10.1038/s41586-020-2604-2 -
Redox Biology Dec 2022Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal...
Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults. Here, we report that even in healthy older men low grade bacterial endotoxemia is prevalent. In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.
Topics: Animals; Mice; Aging; Arginase; Arginine; Endotoxemia; Intestines; Nitric Oxide
PubMed: 36356464
DOI: 10.1016/j.redox.2022.102528 -
Seminars in Cell & Developmental Biology Jun 2017The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands,... (Review)
Review
The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands, the intestine has evolved a mechanism to expand the absorptive surface area by undergoing a morphogenetic process to generate finger-like units called villi. These villi house specialized cell types critical for both absorbing nutrients from food, and for protecting the host from commensal and pathogenic microbes present in the adult gut. In this review, we will discuss mechanisms that coordinate intestinal development, growth, and maturation of the small intestine, starting from the formation of the early gut tube, through villus morphogenesis and into early postnatal life when the intestine must adapt to the acquisition of nutrients through food intake, and to interactions with microbes.
Topics: Cell Differentiation; Endoderm; Humans; Intestines; Morphogenesis
PubMed: 28161556
DOI: 10.1016/j.semcdb.2017.01.011