Review

Authors: Yongyan Chen, Wenwen Cui, Xiao Li...

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

Review

Authors: Nayanan N Nathan, Dana J Philpott, Stephen E Girardin...

Our understanding of the composition and the function of the intestinal microbiota has significantly increased over the past few years. In a series of reviews focusing on the role of the intestinal microbiota in health and disease, we explore recent conceptual and technological advances in this rapidly evolving research arena.

Topics: Animals; Gastrointestinal Microbiome; Health; Humans; Intestines

PubMed: 34146716
DOI: 10.1016/j.micinf.2021.104849

Review

Authors: Sara Viragova, Dong Li, Ophir D Klein...

Tissue regeneration after damage is generally thought to involve the mobilization of adult stem cells that divide and differentiate into progressively specialized progeny. However, recent studies indicate that tissue regeneration can be accompanied by reversion to a fetal-like state. During this process, cells at the injury site reactivate programs that operate during fetal development but are typically absent in adult homeostasis. Here, we summarize our current understanding of the molecular signals and epigenetic mediators that orchestrate "fetal-like reversion" during intestinal regeneration. We also explore evidence for this phenomenon in other organs and species and highlight open questions that merit future examination.

Topics: Regeneration; Humans; Animals; Intestines; Cell Differentiation; Fetus; Signal Transduction

PubMed: 38971147
DOI: 10.1016/j.stem.2024.05.009

Review

Authors: Malin E V Johansson, Daniel Ambort, Thaher Pelaseyed...

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.

Topics: Animals; Enterocytes; Humans; Immunity, Mucosal; Intestinal Mucosa; Intestines; Models, Molecular; Mucins

PubMed: 21947475
DOI: 10.1007/s00018-011-0822-3

Review

Authors: Eloísa Salvo Romero, Carmen Alonso Cotoner, Cristina Pardo Camacho...

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

Authors: Shu-En Wu, Seika Hashimoto-Hill, Vivienne Woo...

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

Authors: Annette Brandt, Anja Baumann, Angélica Hernández-Arriaga...

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

Review

Authors: Alana M Chin, David R Hill, Megan Aurora...

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

Review

Authors: Sylvia Christakos, Shanshan Li, Jessica De La Cruz...

The central role of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. This article describes the early work that served as the foundation for the initial model of vitamin D mediated calcium absorption. In addition, other research related to the role of vitamin D in the intestine, including those which have challenged the traditional model and the crucial role of specific calcium transport proteins, are reviewed. More recent work identifying novel targets of 1,25(OH)D action in the intestine and highlighting the importance of 1,25(OH)D action across the proximal/distal and crypt/villus axes in the intestine is summarized.

Topics: Animals; Calcium; Calcium Channels; Calcium-Binding Proteins; Gene Expression Regulation; Humans; Intestinal Mucosa; Intestines; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

PubMed: 31655181
DOI: 10.1016/j.jsbmb.2019.105501

Authors: J M Smith, M A Skeans, S P Horslen...

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