SCFA: mechanisms and functional importance in the gut

Proceedings of The Nutrition Society, Год журнала: 2020, Номер 80(1), С. 37 - 49

Опубликована: Апрель 2, 2020

In recent years, the importance of gut microbiota in human health has been revealed and many publications have highlighted its role as a key component physiology. Owing to use modern sequencing approaches, characterisation microbiome healthy individuals disease demonstrated disturbance microbiota, or dysbiosis, associated with pathological conditions. The establishes symbiotic crosstalk their host: commensal microbes benefit from nutrient-rich environment provided by produces hundreds proteins metabolites that modulate functions host, including nutrient processing, maintenance energy homoeostasis immune system development. Many bacteria-derived originate dietary sources. Among them, an important attributed derived bacterial fermentation fibres, namely SCFA linking host nutrition intestinal maintenance. are fuels for epithelial cells (IEC) regulate IEC through different mechanisms proliferation, differentiation well subpopulations such enteroendocrine cells, impact motility strengthen barrier metabolism. Recent findings show SCFA, particular butyrate, also immuno-modulatory functions. this review, we discuss on immunity consequently health.

Язык: Английский

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Microbes, metabolites, and the gut–lung axis

Mucosal Immunology, Год журнала: 2019, Номер 12(4), С. 843 - 850

Опубликована: Апрель 11, 2019

Язык: Английский

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Regulation of Intestinal Barrier Function by Microbial Metabolites

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2021, Номер 11(5), С. 1463 - 1482

Опубликована: Янв. 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

Язык: Английский

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The role of short-chain fatty acids in immunity, inflammation and metabolism

Critical Reviews in Food Science and Nutrition, Год журнала: 2020, Номер 62(1), С. 1 - 12

Опубликована: Дек. 1, 2020

Short-chain fatty acids (SCFAs) are carboxylic with carbon atom numbers less than 6, which important metabolites of gut microbiome. Existing research shows that SCFAs play a vital role in the health and disease host. First, key energy source for colon ileum cells, affect intestinal epithelial barrier defense functions by regulating related gene expression. Second, regulate function innate immune cells to participate system, such as macrophages, neutrophils dendritic cells. Third, can also differentiation T B antigen-specific adaptive immunity mediated them. Besides, raw materials sugar lipid synthesis, provides theoretical basis studying potential homeostasis metabolism. There studies showing inhibit tumor cell proliferation promote apoptosis. In this article, we summarized detail immunity, inflammation metabolism, briefly introduced survival. It systematic study drugs human health.

Язык: Английский

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Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota

Nutrients, Год журнала: 2023, Номер 15(9), С. 2211 - 2211

Опубликована: Май 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.

Язык: Английский

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Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(4), С. 866 - 877

Опубликована: Март 11, 2021

Язык: Английский

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Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota–Immune System Interplay. Implications for Health and Disease

Nutrients, Год журнала: 2021, Номер 13(2), С. 699 - 699

Опубликована: Фев. 22, 2021

The most prevalent diseases of our time, non-communicable (NCDs) (including obesity, type 2 diabetes, cardiovascular and some types cancer) are rising worldwide. All them share the condition an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have common malnutrition related to physiopathology. In this context, diet is greatest modulator system–microbiota crosstalk, much interest, new challenges, arising area precision nutrition as a way towards treatment prevention. It fact that westernized (WD) partly responsible for increased prevalence NCDs, negatively affecting both microbiota system. Conversely, other nutritional approaches, such Mediterranean (MD), positively influence system microbiota, proposed not only potential tool clinical management different disease conditions, but prevention health promotion globally. Thus, purpose review determine regulatory role components WD MD interplay, order understand, create awareness of, over key components.

Язык: Английский

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Lactate/GPR81 signaling and proton motive force in cancer: Role in angiogenesis, immune escape, nutrition, and Warburg phenomenon

Pharmacology & Therapeutics, Год журнала: 2019, Номер 206, С. 107451 - 107451

Опубликована: Дек. 10, 2019

Язык: Английский

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Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(5), С. 1161 - 1171

Опубликована: Апрель 13, 2021

Abstract A mounting body of evidence indicates that dietary fiber (DF) metabolites produced by commensal bacteria play essential roles in balancing the immune system. DF, considered nonessential nutrients past, is now to be necessary maintain adequate levels immunity and suppress inflammatory allergic responses. Short-chain fatty acids (SCFAs), such as acetate, propionate, butyrate, are major DF mostly specialized capable breaking down into simpler saccharides further metabolizing SCFAs. SCFAs act on many cell types regulate a number important biological processes, including host metabolism, intestinal functions, This review specifically highlights regulatory functions system with focus innate adaptive lymphocytes. Current information regarding how lymphoid cells, T helper cytotoxic B cells these impact immunity, inflammation, responses discussed.

Язык: Английский

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Compartmentalised acyl-CoA metabolism and roles in chromatin regulation

Molecular Metabolism, Год журнала: 2020, Номер 38, С. 100941 - 100941

Опубликована: Фев. 14, 2020

Many metabolites serve as important signalling molecules to adjust cellular activities and functions based on nutrient availability. Links between acetyl-CoA metabolism, histone lysine acetylation, gene expression have been documented studied over the past decade. In recent years, several additional acyl modifications residues identified, which depend acyl-coenzyme A thioesters (acyl-CoAs) donors. Acyl-CoAs are intermediates of multiple distinct metabolic pathways, substantial evidence has emerged that acylation is metabolically sensitive. Nevertheless, sources acyl-CoAs used for chromatin modification in most cases remain poorly understood. Elucidating how these diverse chemical coupled regulated by metabolism deciphering their functional significance. this article, we review pathways produce acyl-CoAs, well emerging roles regulation. Because extensively reviewed elsewhere, will focus four other acyl-CoA integral major also known modify histones: succinyl-CoA, propionyl-CoA, crotonoyl-CoA, butyryl-CoA. We briefly mention species, present opportunities further research; malonyl-CoA, glutaryl-CoA, 3-hydroxybutyryl-CoA, 2-hydroxyisobutyryl-CoA, lactyl-CoA. Each species indicating potential report shifts status cell. For each metabolite, consider it participates from derived, compartmentalisation its factors reported influence abundance nuclear highlight biological metabolically-linked marks. Finally, aim illuminate key questions they relate control modification. majority annotated mitochondrial processes. Since not be directly transported across membranes, must synthesized outside mitochondria potentially within nucleus participate Thus, subcellular likely plays a role regulation acylation. Metabolite tracing combination with targeting relevant enzymes transporters help map connect The specific function may determined part biochemical properties affect propensity enzymatic versus non-enzymatic protein modification, various can add, remove bind Further, competitive inhibitory effects different make determining relative contexts understand An improved more nuanced understanding physiological disease-related processes emerge answered.

Язык: Английский

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