Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 326, P. 117966 - 117966
Published: Feb. 22, 2024
Language: Английский
Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2021, Volume and Issue: 11(5), P. 1463 - 1482
Published: Jan. 1, 2021
The human gastrointestinal tract (GI) harbors a diverse population of microbial life that continually shapes host pathophysiological responses. Despite readily available abundant metagenomic data, the functional dynamics gut microbiota remain to be explored in various health and disease conditions. Microbiota generate variety metabolites from dietary products influence functions. Since are produced close proximity epithelium, presumably they have significant impact on barrier function immune goal this review is discuss recent advances regulation intestinal function. While mechanisms action these only beginning emerge, mainly point small group shared pathways control Amidst expanding technology broadening knowledge, exploitation beneficial their restore balance will likely prove an extremely useful remedial tool. SummaryGut proximal regulate numerous responsive activities. Current article highlights area as well potential translational applications regulating disorders. Gut Humans microbes coevolved over millions years, thereby contributing interdependency physiological activities.1Li M. Wang B. Zhang Rantalainen S. Zhou H. Y. Shen J. Pang X. Wei Chen Lu Zuo Su Qiu Jia W. Xiao C. Smith L.M. Yang Holmes E. Tang Zhao G. Nicholson J.K. Li L. Symbiotic modulate metabolic phenotypes.Proc Natl Acad Sci U S A. 2008; 105: 2117-2122Crossref PubMed Scopus (755) Google Scholar Diverse interactive associations cells lead mild severe cellular molecular responses depending status Deciphering underlying relationship between community provides unique opportunity utilize prevent treat disorders maintain overall health. Increasing culture-independent omic-based technologies such biomarker sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics facilitated discovery novel microbiota2Oh Byrd A.L. Deming Conlan Program N.C.S. Kong H.H. Segre J.A. Biogeography individuality shape skin metagenome.Nature. 2014; 514: 59-64Crossref (442) Scholar, 3Lynch S.V. Pedersen O. microbiome disease.N Engl J Med. 2016; 375: 2369-2379Crossref (879) 4Human Microbiome Project CStructure, diversity healthy microbiome.Nature. 2012; 486: 207-214Crossref (5255) 5Eckburg P.B. Bik E.M. Bernstein C.N. Purdom Dethlefsen Sargent Gill S.R. Nelson K.E. Relman D.A. Diversity flora.Science. 2005; 308: 1635-1638Crossref (4674) with pathophysiology.6Kamada N. G.Y. Inohara Nunez Control pathogens pathobionts by microbiota.Nat Immunol. 2013; 14: 685-690Crossref (662) 7Ha C.W. Lam Y.Y. A.J. Mechanistic links dynamics, functions health.World Gastroenterol. 20: 16498-16517Crossref 8Wu Tremaroli V. Backhed F. Linking diseases: systems biology perspective.Trends Endocrinol Metab. 2015; 26: 758-770Abstract Full Text PDF (87) 9Claesson M.J. Jeffery I.B. Conde Power S.E. O'Connor Cusack Harris H.M. Coakley Lakshminarayanan O'Sullivan Fitzgerald G.F. Deane Harnedy K. O'Mahony D. van Sinderen Wallace Brennan Stanton Marchesi J.R. A.P. Shanahan Hill Ross R.P. O'Toole P.W. composition correlates diet elderly.Nature. 488: 178-184Crossref (1618) (∼1012–1013) play important role homeostatic leading activities both disease. significantly separates internal organs harmful entities including microorganisms, luminal antigens, proinflammatory factors. Intestinal compromised (barrier dysfunction) several conditions increased translocation bacteria, endotoxins, other inflammatory mediators. dysfunction associated systemic response resulting aggravation diseases. Recent studies shown correlation bowel (IBD), irritable syndrome (IBS), celiac also strongly correlated autoimmune, inflammatory, diseases diabetes, obesity, atherosclerosis, heart failure, hypertension, food allergies, cancer.10Gopalakrishnan Helmink B.A. Spencer Reuben Wargo cancer, immunity, cancer immunotherapy.Cancer Cell. 2018; 33: 570-580Abstract (267) Scholar,11Martini Krug S.M. Siegmund Neurath M.F. Becker Mend your fences: epithelial its mucosal immunity disease.Cell Mol Gastroenterol Hepatol. 2017; 4: 33-46Abstract It has been reported external factors like alcohol, nonsteroidal anti-inflammatory drugs, specific can directly alter pathogenesis diseases.12Elamin Masclee Troost Pieters H.J. Keszthelyi Aleksa Dekker Jonkers Ethanol impairs humans through mitogen activated protein kinase signaling: combined vivo vitro approach.PLoS One. 9e107421Crossref (24) 13Utzeri Usai P. Role non-steroidal drugs permeability nonalcoholic fatty liver disease.World 23: 3954-3963Crossref 14Berkes Viswanathan V.K. Savkovic S.D. Hecht enteric pathogens: effects tight junction barrier, ion transport, inflammation.Gut. 2003; 52: 439-451Crossref (394) imbalance (microbial dysbiosis) linked immature system, wide spectrum intestinal, hepatic, neurological disorders.15Bjarnason I. MacPherson Hollander permeability: overview.Gastroenterology. 1995; 108: 1566-1581Abstract (744) 16Leclercq Matamoros Cani P.D. Neyrinck A.M. Jamar Starkel Windey Verbeke de Timary Delzenne N.M. permeability, gut-bacterial dysbiosis, behavioral markers alcohol-dependence severity.Proc 111: E4485-E4493Crossref (339) 17Gonzalez-Gonzalez Diaz-Zepeda Eyzaguirre-Velasquez Gonzalez-Arancibia Bravo Julio-Pieper Investigating animal models disease.Front Physiol. 9: 1962Crossref (5) 18Frank D.N. St Amand Feldman R.A. Boedeker E.C. Harpaz Pace N.R. Molecular-phylogenetic characterization imbalances diseases.Proc 2007; 104: 13780-13785Crossref (2631) Studies revealed fecal transplantation (FMT) hosts positively reversal, especially those stemming IBD, IBS, disease, Clostridium difficile infections.19Moayyedi Surette M.G. Kim P.T. Libertucci Wolfe Onischi Armstrong Marshall Kassam Z. Reinisch Lee C.H. Fecal induces remission patients active ulcerative colitis randomized controlled trial.Gastroenterology. 149: 102-109.e6Abstract (706) Scholar,20Kim Gadani Abdul-Baki Mitre R. recurrent infection: retrospective single-center chart review.JGH Open. 2019; 3: 4-9Crossref (9) One major metabolism components generation physiology function.21Maurice C.F. Haiser Turnbaugh P.J. Xenobiotics gene expression microbiome.Cell. 152: 39-50Abstract (468) restoration separate cell functions.22Singh Chandrashekharappa Bodduluri Baby B.V. Hegde Kotla N.G. Hiwale A.A. Saiyed T. Patel Vijay-Kumar Langille M.G.I. Douglas G.M. Cheng Rouchka Waigel S.J. Dryden G.W. Alatassi H.G. Haribabu Vemula P.K. Jala V.R. Enhancement integrity metabolite Nrf2 pathway.Nat Commun. 10: 89Crossref (108) 23Ewaschuk J.B. Diaz Meddings Diederichs Dmytrash Backer Looijer-van Langen Madsen K.L. Secreted bioactive Bifidobacterium infantis enhance function.Am Physiol Gastrointest Liver 295: G1025-G1034Crossref (359) 24Anderson R.C. Cookson McNabb W.C. Park McCann Kelly W.J. Roy N.C. Lactobacillus plantarum MB452 enhances increasing levels genes involved formation.BMC Microbiol. 2010; 316Crossref (210) Detailed yet elucidated, but knowledge concerning system gradually. Exploiting tool against In review, we how reinforce via bi-directional interactions cells. Further, treatment strategies mitigate composed 3 main interlinked/interdependent layers physical bacterial intrusion lumen. These include mucus layer, layer formed continuous sheet cells, third, forms system. acts immunological defense viruses, environmental toxins. selectively permeable allow for essential nutrients, electrolytes, amino acids, short-chain acids (SCFAs), sugars, water, select lumen into circulation. single interspersed functionally specialized differentiated enterocytes, Paneth goblet tuft enteroendocrine microfold which together form polarized monolayer separation lamina propria (Table 1). Among these, present intestine, whereas intestine colon, reviewed previously.25Peterson L.W. Artis cells: regulators homeostasis.Nat Rev 141-153Crossref (1145) 26Okumura Takeda Roles maintenance homeostasis.Exp 49: e338Crossref 27Allaire J.M. Crowley Law H.T. Chang S.-Y. Ko H.-J. Vallance epithelium: central coordinator immunity.Trends 39: 677-696Abstract (159) layer28Corfield interaction human.Microorganisms. 6: 78Crossref Scholar,29Corfield Carroll Myerscough Probert C.S. Mucins Biosci. 2001; D1321-D1357Crossref different types distinct roles maintaining homeostasis.Table 1Cell Types Barrier Their FunctionCell typesRole functionEnterocytes (small colon)•Responsible junctional complexes.•Nutrient absorption metabolization.•Balance shedding.•Secretion antimicrobial agents.•Changes expression/localization proteins permeability.Paneth intestine)•Source AMPs.•Directly sense critical homeostasis.•Paneth triggers inflammation dysfunction.•Lack leads necrotizing enterocolitis mice.Goblet intestine)•Produce release MUCs, forming glycoprotein barrier.•Lack MUC2 or O-glycan N-glycosylation susceptibility colitis.Tuft colon)•Secrete IL-25 IL-13 type 2 innate lymphoid (ILC2) promote hyperplasia mucin production.•Detect helminth infection expulse.Enteroendocrine colon)•Secret hormones GLP-2.•GLP-2 TJ ZO-1 occludin attenuates TNF-α–induced changes colon cells.•GLP-2 wound healing TGF-β–dependent manner.M intestine)•Antigen uptake.•M damage, during chronic elevates uptake microorganisms amplifying condition dysfunction.AMP, peptide; GLP-2, glucagon-like peptide-2; M cell, cell; MUC, mucin; TGF-β, transforming growth factor beta; TJ, junction; TNF-α, tumor necrosis alpha. Open table new tab AMP, (IECs) selective penetration electrolytes while simultaneously excluding pathogen-associated pattern, toxins, foreign antigens.30Kunzelmann Mall Electrolyte transport mammalian colon: implications disease.Physiol Rev. 2002; 82: 245-289Crossref Enterocytes connect each adhesive make up (TJ) proteins, adherens (AJ) gap desmosomes 2).31Niessen C.M. Tight junctions/adherens junctions: basic structure function.J Invest Dermatol. 127: 2525-2532Abstract (410) Scholar,32Groschwitz K.R. Hogan S.P. function: pathogenesis.J Allergy Clin 2009; 124 (quiz 21–22): 3-20Abstract (766) complexes not mechanically secure extracellular interactions, intracellular adaptor protein–mediated within Epithelial tightly paracellular (space cells) transcellular (through cell) posttranslational modifications proteins.33Van Itallie Anderson Claudins transport.Annu 2006; 68: 403-429Crossref (837) 34Fung K.Y.Y. Fairn G.D. W.L. Transcellular vesicular endothelial challenges opportunities.Traffic. 19: 5-18Crossref (47) 35Shigetomi Ikenouchi Regulation post-translational membrane proteins.J Biochem. 163: 265-272Crossref (0) located apical side belt-like ring at lateral membrane. consist 50 crucial cell-to-cell adhesion health.36Chiba Osanai Murata Kojima Sawada Transmembrane junctions.Biochim Biophys Acta. 1778: 588-600Crossref (276) Some tetraspan single-span transmembrane link cytoskeletal proteins.37Schulzke J.D. Fromm meets function.Ann N Y Sci. 1165: 1-6Crossref (1) (OCLN), claudin (CLDN), tricellulin molecules proteins.38Furuse Hirase Itoh Nagafuchi Yonemura Tsukita Occludin: integral localizing junctions.J Cell Biol. 1993; 123: 1777-1788Crossref (1975) 39Furuse Fujita Hiiragi Fujimoto Claudin-1 -2: junctions no sequence similarity occludin.J 1998; 141: 1539-1550Crossref (1554) 40Ikenouchi Furuse Sasaki Tricellulin constitutes tricellular contacts cells.J 171: 939-945Crossref (535) 41Garrido-Urbani Bradfield P.F. Imhof dynamics: (JAMs).Cell Tissue Res. 355: 701-715Crossref (64) Other zonula occludens (ZO) (ZO-1, ZO-2, ZO-3) scaffold proteins. postsynaptic density protein-95/Drosophila disc large suppressor/ZO-1 (PDZ) binding domains plaque (eg, F-actin) complex.42Odenwald M.A. Choi Kuo W.T. Singh Sailer Fanning A.S. Turner scaffolding coordinates actomyosin specializations vivo.J Biol Chem. 293: 17317-17335Abstract (20) seals generally when anastomose adjacent based size/charge space. Adherence primarily contribute mechanical structures, properties, extensively elsewhere.43Garcia-Hernandez Quiros Nusrat claudins: homeostasis inflammation.Ann 1397: 66-79Crossref (104) 44Laukoetter Bruewer complex.Curr Opin 22: 85-89Crossref (173) 45Buckley disease.Cold Spring Harb Perspect A02931Crossref (110) 46Farkas A.E. Pharmacological targeting inflamed barrier.Curr Pharm Des. 5400-5414Crossref (3) 47Choi Yeruva Contributions barriers disease.Exp 358: 71-77Crossref (29) 48Zuo targets effectors homeostasis.Cell 2020; 327-340Abstract ScholarTable 2Structural Components Cells FunctionStructural componentsJunctional proteinsExamples dysfunctionTight proteinsZO, occludin, claudins, tricellulin, JAM•IFN-γ TNF-α mediated organization ZO-1, claudin-1, claudin-4, occluding, JAM-A downregulate function.•Downregulation claudin-3, claudin-5, claudin-8 claudin-2 MLCK phosphorylation function.Adherens proteinsCadherins, catenins•Downregulated E-cadherin–catenin complex mediates impairment barrier.DesmosomeDesmoglein, desmocollins•Desmoglein (Dsg2) deficiency loss integrity.Gap junctionsConnexin•Connexin-43 plays intercellular communication vesicles, tunneling nanotubes junctions.IFN-γ, interferon gamma; JAM, molecules; MLCK, myosin light-chain kinase; alpha; ZO, occludens. IFN-γ, disruption AJ, causing dysregulated translocation/transportation mediators, potentially manifests inflammation. Increased further perpetuates permeability. following sections describe altered state Defective combination dysregulation tract–related limited drug-induced toxicity, cancer. occurs apoptosis/enterocyte death, degradation, due TJs. independently regulated consequences other. section describes responsible dysfunction. As described previous sections, was solutes water cross TJs size charge selectivity: pore pathway48Zuo 49Turner disease.Nat 799-809Crossref (1727) 50Anderson Van Physiology junction.Cold 1: a002584Crossref (563) leak pathway.48Zuo Scholar,51Buschmann M.M. Rajapakse Raleigh D.R. Lingaraju Zha Abbott McAuley Breskin L.A. Wu Weber C.R. Occludin OCEL-domain required macromolecular flux.Mol 24: 3056-3068Crossref (94) pathway exclusively excludes diameter ≤8 Å high-conductance route. CLDN-2 CLDNs 10a, 10b, 15, 16, 17 were pathway. contrast pathway, allows macromolecule flux exclusion limit ∼100 lower conductance.51Buschmann believed (MLCK), where constitutively sufficient increase pathway–dependent vivo.52Shen Black E.D. Witkowski Lencer W.I. Guerriero Schneeberger E.E. Myosin light chain regulates remodeling structure.J 119: 2095-2106Crossref (308) Scholar,53Su Clayburgh Nalle S.C. Sullivan E.A. Abraham Targeted causes activation contributes development experimental colitis.Gastroenterology. 136: 551-563Abstract (273) OCLN, pathway.54Yu McCarthy K.M. Francis S.A. McCormack Lai Rogers Lynch R.D. Knockdown phenotypic alterations cells.Am 288: C1231-C1241Crossref (239) discussions published.48Zuo Scholar,49Turner 9
Language: Английский
Citations
475
Nutrients, Journal Year: 2023, Volume and Issue: 15(9), P. 2211 - 2211
Published: May 6, 2023
Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis their deficiency is involved the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, cardiometabolic disorders. SCFAs are metabolites specific bacterial taxa human microbiota, production influenced by foods or food supplements, mainly prebiotics, direct fostering these taxa. This Review provides an overview SCFAs’ roles functions, SCFA-producing bacteria, from microbiological characteristics taxonomy to biochemical process that lead release SCFAs. Moreover, we will describe potential therapeutic approaches boost levels treat different related diseases.
Language: Английский
Citations
423
Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 19(12), P. 753 - 767
Published: July 29, 2022
Language: Английский
Citations
177
Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(2), P. 1487 - 1564
Published: Dec. 15, 2022
Of all the organ systems in body, gastrointestinal tract is most complicated terms of numbers structures involved, each with different functions, and types signaling molecules utilized. The digestion food absorption nutrients, electrolytes, water occurs a hostile luminal environment that contains large diverse microbiota. At core regulatory control digestive defensive functions enteric nervous system (ENS), complex neurons glia gut wall. In this review, we discuss 1) intrinsic neural involved 2) how ENS interacts immune system, microbiota, epithelium to maintain mucosal defense barrier function. We highlight developments have revolutionized our understanding physiology pathophysiology control. These include new molecular architecture ENS, organization function motor circuits, roles glia. explore transduction stimuli by enteroendocrine cells, regulation intestinal glia, local role microbiota regulating structure ENS. Multifunctional work together glial macrophages, interstitial cells integrating an array signals initiate outputs are precisely regulated space time homeostasis.
Language: Английский
Citations
150
Inflammatory Bowel Diseases, Journal Year: 2021, Volume and Issue: 28(4), P. 639 - 648
Published: Dec. 6, 2021
Abstract Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium destruction intestinal homeostasis, which has caused a huge social economic burden on health system all over world. Its pathogenesis multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, dysregulated immune response. Thus far, although cells have become focus most research, it increasingly clear that play important role in progression UC. Notably, apoptosis vital catabolic process cells, crucial to maintain stability environment regulate ecology. In this review, mechanism induced reactive oxygen species endoplasmic reticulum stress, as well excessive dysfunction gut microbiology imbalance are systematically comprehensively summarized. Further understanding UC may provide novel strategy for its therapy clinical practices development new drugs.
Language: Английский
Citations
132
Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1595 - 1619
Published: Aug. 23, 2023
Abstract Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed death. Thus, dysfunctional eventually lead or contribute to age-related diseases, such neurodegenerative, cardiovascular diseases. mitochondrion-associated death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli maintain homeostasis via mitohormesis, unfolded protein response, mitophagy. The also presents details on forms mitochondria-associated death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, paraptosis, highlights their involvement disease pathogenesis, collectively suggesting directions further research.
Language: Английский
Citations
124
Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(8), P. 537 - 555
Published: May 13, 2024
Language: Английский
Citations
22
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 7, 2025
The intestinal epithelium, beyond its role in absorption and digestion, serves as a critical protective mechanical barrier that delineates the luminal contents gut microbiota from lamina propria within resident mucosal immune cells to maintain homeostasis. is manifested contiguous monolayer of specialized epithelial (IEC), interconnected through tight junctions (TJs). integrity this paramount. Consequently, excessive IEC death advances permeability consequence thereof translocation bacteria into propria, subsequently triggering an inflammatory response, which underpins clinical disease trajectory bowel (IBD). A burgeoning body evidence illustrates landscape where undergoes several model programmed cell (PCD) pathophysiology pathogenesis IBD. Apoptosis, necroptosis, pyroptosis represent principal modalities PCD with intricate specific pathways molecules. Ample has revealed substantial mechanistic convergence crosstalk among these three aforementioned forms death, expanding conceptualization PANoptosis orchestrated by PNAoptosome complex. This review provides concise overview molecular mechanisms apoptosis, pyroptosis. Furthermore, based on between deaths IEC, details current knowledge regarding regulation natural products. Our objective broaden comprehension innovative underlying IBD furnish foundation for developing more drugs treatment IBD, benefiting both practitioners research workers.
Language: Английский
Citations
3
Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(781)
Published: Jan. 15, 2025
Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, molecular mechanisms failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in cells (IECs) patients with IBD and show that impaired sufficient to drive chronic inflammation. We found reduced expression fusion–related genes, such as dynamin-related guanosine triphosphatase (GTPase) optic atrophy 1 ( OPA1 ), fragmented networks crypt IECs IBD. Mice Opa1 deficiency gut epithelium i∆IEC ) spontaneously developed inflammation mucosal ulcerations immune cell infiltration. Intestinal mice was driven by microbial translocation associated progenitor death dysfunction. -deficient human organoids exposed pharmacological inhibitor showed disruption network fragmentation changes size, ultrastructure, function, resembling observed patient samples. Pharmacological inhibition GTPase dynamin-1–like protein derived from partially reverted this phenotype. Together, our data role for regulating homeostasis function. Our provide mechanistic explanation dysfunction identify potential therapeutic target disease.
Language: Английский
Citations
3
The Lancet. Gastroenterology & hepatology, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
SummaryThe intestinal barrier serves as a boundary between the mucosal immune system in lamina propria and external environment of lumen, which contains diverse array microorganisms ingested environmental factors, including pathogens, food antigens, toxins, other foreign substances. This has central role regulating controlled interaction luminal factors system. Disruptions epithelial cells, serve physical barrier, or antimicrobial peptides mucins they produce, act chemical can lead to leaky gut. In this state, wall is unable efficiently separate flora contents from The subsequent activation an important pathogenesis inflammatory bowel disease, well metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, colorectal cancer. Dysregulated integrity also been described patients with chronic diseases outside gastrointestinal tract, rheumatoid arthritis neurodegenerative disorders. Mechanistic studies dysfunction have revealed that local systemic circulation activated cells cytokines secrete, extracellular vesicles, promote proinflammatory processes within tract. Review, we summarise these findings highlight several new therapeutic concepts currently being developed attempt control via direct indirect modulation function.
Language: Английский
Citations
2