Interaction between microbiota and immunity in health and disease

Cell Research, Journal Year: 2020, Volume and Issue: 30(6), P. 492 - 506

Published: May 20, 2020

Abstract The interplay between the commensal microbiota and mammalian immune system development function includes multifold interactions in homeostasis disease. microbiome plays critical roles training of major components host’s innate adaptive system, while orchestrates maintenance key features host-microbe symbiosis. In a genetically susceptible host, imbalances microbiota-immunity under defined environmental contexts are believed to contribute pathogenesis multitude immune-mediated disorders. Here, we review microbiome-immunity crosstalk their health disease, providing examples molecular mechanisms orchestrating these intestine extra-intestinal organs. We highlight aspects current knowledge, challenges limitations achieving causal understanding host immune-microbiome interactions, as well impact on diseases, discuss how insights may translate towards future microbiome-targeted therapeutic interventions.

Language: Английский

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The intestinal microbiota fuelling metabolic inflammation

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 40 - 54

Published: Aug. 6, 2019

Language: Английский

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Microfluidic Organ-on-a-Chip Models of Human Intestine

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2018, Volume and Issue: 5(4), P. 659 - 668

Published: Jan. 1, 2018

Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology pathophysiology. In this article, we review field describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability analyze contributions individual cellular, chemical, physical control parameters one-at-a-time; coculture cells commensal microbiome for extended times; create human-relevant disease models. We also discuss potential future applications Chips, they might be drug development personalized medicine. SummaryOrgans-on-chips are cell that recapitulate structure, function, physiology, pathology living organs in vitro. recent various intestine-on-a-chip their value modeling, discovery, Organs-on-chips The major organ function is carry out digestion, absorption, secretion, motility,1Silverthorn D.U. Ober W.C. Garrison C.W. Silverthorn A.C. Johnson B.R. Human physiology: an integrated approach. Pearson/Benjamin Cummings, San Francisco2009Google Scholar addition establishing a protective epithelial barrier between digestive environment body. addition, intestines regulate systemic by metabolizing drugs2Benet L.Z. Wu C.-Y. Hebert M.F. Wacher V.J. Intestinal metabolism antitransport processes: paradigm shift oral delivery.J Control Release. 1996; 39: 139-143Crossref Scopus (188) Google Scholar; communicate other organs, such as liver3Moore F.A. Moore E.E. Poggetti R. McAnena O.J. Peterson V.M. Abernathy C.M. Parsons P.E. Gut bacterial translocation via portal vein: clinical perspective torso trauma.J Trauma Acute Care Surg. 1991; 31: 629-638Crossref (447) Scholar, 4Bloemen J.G. Venema K. van de Poll M.C. Damink S.W.O. Buurman W.A. Dejong C.H. Short chain fatty acids exchange across gut liver humans measured at surgery.Clin Nutr. 2009; 28: 657-661Abstract Full Text PDF PubMed (217) pancreas,5Ahuja M. Schwartz D.M. Tandon Son A. Zeng Swaim W. Eckhaus Hoffman V. Cui Y. Xiao B. Orai1-mediated antimicrobial secretion from pancreatic acini shapes regulates innate immunity.Cell Metab. 2017; 25: 635-646Abstract (84) flow; contain enteric nervous system forms part gut-brain axis.6Cryan J.F. Dinan T.G. Mind-altering microorganisms: impact microbiota on brain behaviour.Nat Rev Neurosci. 2012; 13: 701-712Crossref (2487) 7Mayer E.A. feelings: emerging biology gut–brain communication.Nat 2011; 12: 453-466Crossref (986) site which microbes live interact lymphoid tissues host immune system, contributes significantly homeostasis.8Garrett W.S. Gordon J.I. Glimcher L.H. Homeostasis inflammation intestine.Cell. 2010; 140: 859-870Abstract (556) 9Round J.L. Mazmanian S.K. responses during health disease.Nat Immunol. 9: 313-323Crossref (3250) For example, its metabolites (eg, short-chain acids) recently shown play central role maintenance health, modulation, both enteral nonenteral diseases.10Wong J.M. De Souza Kendall Emam Jenkins D.J. Colonic health: fermentation short acids.J Clin Gastroenterol. 2006; 40: 235-243Crossref (1832) 11Smith P.M. Howitt M.R. Panikov N. Michaud Gallini C.A. Bohlooly-y Glickman J.N. Garrett microbial metabolites, acids, colonic Treg homeostasis.Science. 2013; 341: 569-573Crossref (3048) However, analysis interactions has limited genetic metagenomics because it these epithelium more than about 1 day using even sophisticated cultures. Thus, there great efforts develop experimental vitro ex vivo permit pathophysiology presence absence microbiome. most common model absorption involve culturing established line Caco-212Hidalgo I.J. Raub T.J. Borchardt R.T. Characterization colon carcinoma (Caco-2) permeability.Gastroenterology. 1989; 96: 736-749Abstract (1952) 13Artursson P. Karlsson J. Correlation apparent permeability coefficients cells.Biochem Biophys Res Commun. 175: 880-885Crossref (1674) HT-2914Pinto M.G.V. Gómez Seifert S. Watzl Holzapfel W.H. Franz Lactobacilli stimulate response modulate TLR expression HT29 vitro.Int J Food Microbiol. 133: 86-93Crossref (113) 15Eveillard Fourel Bare Kernéis Coconnier M.H. Karjalainen T. Bourlioux Servin A.L. Identification characterization adhesive factors Clostridium difficile involved adhesion enterocyte-like Caco-2 mucus-secreting culture.Mol 1993; 7: 371-381Crossref (74) cells) extracellular matrix (ECM)-coated, porous membranes within Transwell insert devices. Although commonly pharmaceutical industry, 2-dimensional (2D) format fails physiological 3-dimensional (3D) tissue morphology re-establish key differentiated functions mucus production, villi formation, cytochrome P-450-based metabolism).16Kim H.J. Huh D. Hamilton G. Ingber D.E. gut-on-a-chip inhabited flora experiences peristalsis-like motions flow.Lab Chip. 2165-2174Crossref (1046) 17Kim Gut-on-a-Chip microenvironment induces undergo villus differentiation.Integr Biol. 5: 1130-1140Crossref (443) These static cannot support cells, critical physiology,16Kim bacteria rapidly overgrow contaminate cultures day. Several models, everted sac18Alam M.A. Al-Jenoobi F.I. Al-mohizea A.M. Everted sac tool research: limitations applications.J Pharm Pharmacol. 64: 326-336Crossref (131) Ussing chamber,19Rozehnal Nakai Hoepner U. Fischer Kamiyama E. Takahashi Yasuda Mueller small mounted chamber characterizing drugs.European Journal Pharmaceutical Sciences. 46: 367-373Crossref (104) 20Smith Mirabelli C. Fondacaro Ryan F. Dent 5-fluorouracil absorption: Use chambers assess transport metabolism.Pharm Res. 1988; 598-603Crossref (45) assays; however, expected lifespan (<8 hours) sufficient enable many studies normal clinically relevant host-microbiome crosstalk. had technically challenging primary 3D derived either crypts containing endogenous induced pluripotent stem revolutionized maintaining niches supporting differentiation subtypes vitro.21Sato Van Es J.H. Snippert Stange Vries R.G. Den Born Barker Shroyer N.F. Wetering Clevers H. Paneth constitute niche Lgr5 crypts.Nature. 469: 415-418Crossref (1723) 22Jung Sato Merlos-Suárez Barriga F.M. Iglesias Rossell Auer Gallardo Blasco Sancho Isolation expansion cells.Nat Med. 17: 1225-1227Crossref (497) When cultured ECM gel medium Wnt, R-spondin, noggin, growth factors, organoids (enteroids) spontaneously villus-crypt morphologic organization histogenesis.22Jung Each biopsy patient can grown, frozen, revived multiple reuses, potentially establish biobanks23van Francies H.E. Francis Bounova Iorio Pronk Houdt Gorp Taylor-Weiner Kester L. Prospective derivation biobank colorectal cancer patients.Cell. 2015; 161: 933-945Abstract (1348) 24Sato SnapShot: growing cells.Cell. 1700-1700.e1Abstract (97) multiplexed screening platforms validating candidates advance medicine.25Fatehullah Tan S.H. Organoids Cell 2016; 18: 246-254Crossref (837) lack types found intestine, endothelium-lined blood vessels important transport, pharmacokinetic (PK) analysis, modeling. They do experience fluid flows cyclic mechanical deformations similar those experienced peristalsing contribute function. Furthermore, each enteroid closed lumen when surrounding gel, experimentally difficult sample manipulate luminal components nutrients, drugs, toxins). This structure limits researchers PK, metabolism), interactions.26Park G.-S. Park Shin Zhao Sheikh Oh S.J. Kim Emulating ecosystem gastrointestinal tract vitro.Stem Rep. 321-334Crossref (43) challenges overcome Organ Chip intestine. devices, originally fabricated methods adapted computer microchip manufacturing soft lithography), continuously perfused arranged simulate tissue- organ-level physiology.27Bhatia S.N. organs-on-chips.Nat Biotechnol. 2014; 32: 760-772Crossref (1976) Over past 5 years, engineered increasing complexity include neighboring channels lined microvascular endothelium, microbes, pathogenic bacteria, some application forces mimic (Figure 1). Next emulate (Table Also considered implications work complex development, medicine future.Table 1Design Characteristics ModelsModelTEERAbsorptionCocultureMicrobiomeDifferentiationPeristalsisDrug metabolismCrypt-villus axisOxygen modulationDisease modelingStatic TranswellYes12Hidalgo ScholarYes12Hidalgo ScholarNoYes14Pinto (<24 h)NoNoNoNoNoNo OrganoidNoYes95Zietek Rath Haller Daniel assessing nutrient sensing incretin secretion.Sci 16831Crossref ScholarNoYes96Zhang Y.G. Xia Sun Salmonella-infected crypt-derived host–bacterial interactions.Physiol 2: e12147Crossref (150) (<1 h)Yes21Sato ScholarNoYes97Lu Rettenmeier Paszek Yueh M.-F. Tukey R.H. Trottier Barbier O. Chen Crypt cytotoxicity studies.Drug Metab Dispos. 45: 748-754Crossref (28) ScholarYes21Sato ScholarNoYes22Jung Ex vivoYes19Rozehnal 98Madsen Cornish Soper McKaigney Jijon Yachimec Doyle Jewell Simone Probiotic enhance murine function.Gastroenterology. 2001; 121: 580-591Abstract (890) ScholarYes19Rozehnal (<3 h)Yes19Rozehnal ScholarNoYes100Sjöberg Å. Lutz Tannergren Wingolf Borde Ungell A.-L. Comprehensive regional prediction fraction absorbed drugs technique.Eur Sci. 48: 166-180Crossref (151) ScholarYes99Worton Candy Wallis Clarke Osborne Haddon Stephen Studies early association Salmonella typhimurium mucosa vitro: relationship virulence.J Med 29: 283-294Crossref (31) ScholarYes98Madsen ScaffoldNoNoNoNoYes40Wang Gunasekara D.B. Reed M.I. DiSalvo Bultman Sims C.E. Magness S.T. Allbritton N.L. A microengineered collagen scaffold generating polarized crypt-villus architecture epithelium.Biomaterials. 128: 44-55Crossref (191) ScholarNoNoYes40Wang ScholarNoNoMicrofluidic 2-channelYes32Maoz B.M. Herland Henry O.Y.F. Leineweber Yadid Mannix Kujala Fitzgerald Parker K.K. combined multi-electrode array transepithelial electrical resistance measurement capabilities.Lab 2294-2302Crossref ScholarYes30Gao Liu Lin J.-M. Wang Jiang monolayers mass spectrometry membrane-based device.Lab 978-985Crossref (94) ScholarYes37Esch M.B. Mahler G.J. Stokol Shuler M.L. Body-on-a-chip simulation suggests ingested nanoparticles cause injury.Lab 14: 3081-3092Crossref ScholarNoNoNoYes39Shim K.-Y. Lee Han Nguyen N.-T. Sung three-dimensional structure.Biomed Microdevices. 19: 37Crossref (120) ScholarYes39Shim ScholarNoNo vivoNoYes99Worton ScholarNoNoYes101Dawson Dyer Macfie Davies Karsai Greenman Jacobsen chip based full thickness dual flow.Biomicrofluidics. 10: 064101Crossref (32) ScholarNoYes101Dawson Multichannel (HuMiX)Yes41Shah Fritz J.V. Glaab Desai M.S. Greenhalgh Frachet Niegowska Estes Jäger Seguin-Devaux microfluidics-based human–microbe interface.Nat 11535Crossref (326) ScholarNoNoYes41Shah h)NoNoNoNoYes41Shah ScholarNo ChipYes16Kim 42Kim Li Collins J.J. Contributions deformation overgrowth gut-on-a-chip.Proc Natl Acad 113: E7-E15Crossref (549) ScholarYes16Kim ScholarNoYes16Kim (>7 d)Yes17Kim ScholarNoYes42Kim ScholarTEER, resistance. Open table tab TEER, devices hollow microchannels less mm width laminar flow nanoliter microliter scale volumes, thus, amenable use cells. By syringe peristaltic pump, may desired rates through microchannel, dynamic ranges associated shear stresses surface observed lumen,28Vickerman Blundo Chung Kamm Design, fabrication implementation novel multi-parameter platform real-time imaging.Lab 2008; 8: 1468-1477Crossref (294) 29Tanaka Yamato Okano Kitamori Evaluation effects stress hepatocytes microchip-based system.Meas Sci Technol. 3167-3170Crossref (87) capillaries. fluidic enables delivery compounds, toxins grown highly regulated spatiotemporal manner. Most 2 separated porous, ECM-coated polyester polycarbonate membrane, immortalized surfaces.30Gao monolayer formed device c

Language: Английский

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Organ Failure Due to Systemic Injury in Acute Pancreatitis

Gastroenterology, Journal Year: 2019, Volume and Issue: 156(7), P. 2008 - 2023

Published: Feb. 12, 2019

Language: Английский

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Microbiota in pancreatic health and disease: the next frontier in microbiome research

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2019, Volume and Issue: 17(1), P. 53 - 64

Published: Dec. 6, 2019

Language: Английский

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Intestinal microbiota enhances pancreatic carcinogenesis in preclinical models

Carcinogenesis, Journal Year: 2018, Volume and Issue: 39(8), P. 1068 - 1078

Published: May 25, 2018

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in United States yet data are scant regarding host factors influencing pancreatic carcinogenesis. Increasing evidence support role microbiota carcinogenesis but its PDAC not well established. Herein, we report that antibiotic-mediated microbial depletion KrasG12D/PTENlox/+ mice showed a decreased proportion poorly differentiated tumors compared to microbiota-intact mice. Subsequent 16S rRNA PCR ~50% with harbored intrapancreatic bacteria. To determine if similar observation humans correlates presence PDAC, benign and malignant human surgical specimens demonstrated by bacterial sequencing culture confirmation. However, composition did differentiate from non-PDAC tissue. Furthermore, murine pancreas naturally acquire microbiota, as germ-free transferred specific pathogen-free housing failed bacteria over time, which was augmented model colitis. Finally, Nod-SCID mice, microbiota-intact, increased time xenograft formation, smaller tumors, attenuated growth. Interestingly, both cohorts were devoid intratumoral PCR, suggesting intrapancreatic/intratumoral sole driver acceleration. Xenografts innate immune suppression immunohistochemistry differential regulation oncogenic pathways determined RNA sequencing. Our work supports long-distance intestinal on progression opens new research avenues

Language: Английский

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Role of gut microbiota on intestinal barrier function in acute pancreatitis

World Journal of Gastroenterology, Journal Year: 2020, Volume and Issue: 26(18), P. 2187 - 2193

Published: May 14, 2020

Acute pancreatitis (AP) is a common gastrointestinal disorder.Approximately 15%-20% of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction may be caused by the massive release cytokines in early stage AP, followed intestinal pancreatic necrosis later stage.A study showed that 59% AP had associated barrier injury, with increased mucosal permeability, leading to bacterial translocation, tissue infection, occurrence syndrome.However, real effect gut microbiota its metabolites on function remains unclear.This review summarizes alterations flora during development progression unveil mechanism failure AP.

Language: Английский

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Intestinal Barrier and Permeability in Health, Obesity and NAFLD

Biomedicines, Journal Year: 2021, Volume and Issue: 10(1), P. 83 - 83

Published: Dec. 31, 2021

The largest surface of the human body exposed to external environment is gut. At this level, intestinal barrier includes luminal microbes, mucin layer, gastrointestinal motility and secretion, enterocytes, immune cells, gut vascular barrier, liver barrier. A healthy characterized by selective permeability nutrients, metabolites, water, bacterial products, processes are governed cellular, neural, immune, hormonal factors. Disrupted (leaky syndrome) can represent a predisposing or aggravating condition in obesity metabolically associated steatosis (nonalcoholic fatty disease, NAFLD). In what follows, we describe morphological-functional features role major modifiers discuss recent evidence pointing key obesity/NAFLD.

Language: Английский

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Activated regulatory T-cells promote duodenal bacterial translocation into necrotic areas in severe acute pancreatitis

Gut, Journal Year: 2023, Volume and Issue: 72(7), P. 1355 - 1369

Published: Jan. 11, 2023

In acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease late death. Understanding how immunological host defence mechanisms fail to protect intestinal barrier is great importance in reducing mortality disease. Here, we studied role Treg/Th17 balance maintaining function a mouse model AP.AP was induced by partial duct ligation C57Bl/6 or DEREG mice, which regulatory T-cells (Treg) were depleted intraperitoneal injection diphtheria toxin. By flow cytometry, functional suppression assays transcriptional profiling analysed Treg activation characterised lamina propria as well intraepithelial lymphocytes (IELs) regarding their differentiation. Microbiota composition examined samples murine human 16S rRNA gene sequencing.The prophylactic Treg-depletion enhanced proinflammatory response an experimental AP but stabilised Th17 cells CD8+/γδTCR+ IELs. animals developed less pancreas. Duodenal overgrowth facultative pathogenic taxa Escherichia/Shigella associates with infected diminished animals.Tregs play crucial counterbalance against systemic inflammatory syndrome. AP, Treg-activation disturbs duodenal permits commensal bacteria into necrosis. Targeting Tregs may help ameliorate course.

Language: Английский

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Critical role of the gut microbiota in immune responses and cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 14, 2024

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence connections between and cancer immunotherapy. Therefore, understanding functional regulating immune responses to immunotherapy is crucial for developing precision medicine. this review, we extract insights from state-of-the-art research decipher complicated crosstalk among microbiota, systemic system, context Additionally, as can account immune-related adverse events, discuss potential interventions minimize these effects clinical application five microbiota-targeted strategies that precisely increase efficacy Finally, holds promising target immunotherapeutics, summarize current challenges provide general outlook on future directions field.

Language: Английский

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