Cited by 501Gut microbiota and healthGastrointestinal motility and disordersImmune Response and Inflammation

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Microbial Translocation Across the GI Tract

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Brenchley, Jason M., Douek, Daniel C.·2012·Annual Review of Immunology

DOI 10.1146/annurev-immunol-020711-075001PMC PMC3513328

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Abstract

The lumen of the gastrointestinal (GI) tract is home to an enormous quantity of different bacterial species, our microbiota, that thrive in an often symbiotic relationship with the host. Given that the healthy host must regulate contact between the microbiota and its immune system to avoid overwhelming systemic immune activation, humans have evolved several mechanisms to attenuate systemic microbial translocation (MT) and its consequences. However, several diseases are associated with the failure of one or more of these mechanisms, with consequent immune activation and deleterious effects on health. Here, we discuss the mechanisms underlying MT, diseases associated with MT, and therapeutic interventions that aim to decrease it.

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“Moreover, inflammatory conditions can be associated with upregulation of specific channel-forming claudins such as claudin 2 (66, 68).”
Background
Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women
Reid, G., Charbonneau, D., Erb, J., Kochanowski, B., Beuerman, D., Poehner, R., & Bruce, A. W. (2003) · FEMS Immunology & Medical Microbiology · doi:10.1016/s0928-8244(02)00465-0 · Cited by 514
The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis
Sood, A., Midha, V., Makharia, G. K., Ahuja, V., Singal, D., Goswami, P., & Tandon, R. K. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.07.016 · Cited by 513
Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
Ancuta, P., Kamat, A., Kunstman, K. J., Kim, E.-Y., Autissier, P., Wurcel, A., Zaman, T., Stone, D., Mefford, M., Morgello, S., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002516 · Cited by 499
Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections
Estes, J. D., Harris, L. D., Klatt, N. R., Tabb, B., Pittaluga, S., Paiardini, M., Barclay, G. R., Smedley, J. V., Pung, R., Oliveira, K. M., et al. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001052 · Cited by 498
Self-citation
Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis
Zocco, M. A., Verme, L. Z. D., Cremonini, F., Piscaglia, A. C., Nista, E. C., Candelli, M., Novi, M., Rigante, D., Cazzato, I. A., Ojetti, V., et al. (2006) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.02927.x · Cited by 472
Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota
Elson, C. O., Cong, Y., McCracken, V. J., Dimmitt, R. A., Lorenz, R. G., & Weaver, C. T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00291.x · Cited by 469 · cited 1×
“Additionally, altered composition of the GI tract microbiota has also been suggested to play a role in IBD pathogenesis (99, 100), as revealed by mouse models of IBD in which inflammation is significantly reduced when the mice are housed in germ-free conditions (101, 102).”
Background
Probiotics Restore Bowel Flora and Improve Liver Enzymes in Human Alcohol-Induced Liver Injury: A Pilot Study
Kirpich, I., Solovieva, N., Leikhter, S., Shidakova, N. A., Lebedeva, O. V., Sidorov, P., Bazhukova, T. A., Soloviev, A., Barve, S., McClain, C., et al. (2008) · Alcohol · doi:10.1016/j.alcohol.2008.08.006 · Cited by 464
Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay
Fukui, H., Brauner, B., Bode, J. C., & Bode, C. (1991) · Journal of Hepatology · doi:10.1016/0168-8278(91)90933-3 · Cited by 461
The role of the gut microbiota in nonalcoholic fatty liver disease
Abu-Shanab, A., & Quigley, E. M. M. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.172 · Cited by 457
The role of the intestinal microbiota in the development of atopic disorders
Penders, J., Stobberingh, E. E., van den Brandt, P. A., & Thijs, C. T. (2007) · Allergy · doi:10.1111/j.1398-9995.2007.01462.x · Cited by 447
Animal Models of Steatosis
Koteish, A. A., & Diehl, A. M. (2001) · Seminars in Liver Disease · doi:10.1055/s-2001-12932 · Cited by 447
THE LEAKY GUT OF ALCOHOLISM: POSSIBLE ROUTE OF ENTRY FOR TOXIC COMPOUNDS
Bjarnason, I., Ward, K., & Peters, T. B. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92109-3 · Cited by 432
Graft-versus-Host Disease and Survival in Patients with Aplastic Anemia Treated by Marrow Grafts from HLA-Identical Siblings
Storb, R. F., Prentice, R. L., Buckner, C. D., Clift, R. A., Appelbaum, F. R., Deeg, J., Doney, K., Hansen, J. A., Mason, M. W., Sanders, J. E., et al. (1983) · New England Journal of Medicine · doi:10.1056/nejm198302103080602 · Cited by 431
Shedding as a mechanism of down-modulation of CD14 on stimulated human monocytes
Bažil, V., & Strominger, J. L. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.5.1567 · Cited by 430 · cited 1×
“Following LPS stimulation, CD14+ monocytes/macrophages secrete sCD14 and shed surface CD14, which binds to LPS (49, 50).”
Background
Is Lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study
Gupta, P., Andrew, H., Kirschner, B. S., & Guandalini, S. (2000) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200010000-00024 · Cited by 429
Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis
Lumsden, A. B., Henderson, M. J., & Kutner, M. H. (1988) · Hepatology · doi:10.1002/hep.1840080207 · Cited by 427 · cited 1×
“Indeed, concentrations of LPS in the portal vein are higher than in either the hepatic or peripheral veins (40), and bacteria can be cultured from healthy liver explants (41).”
Background
IL-17 Markedly Up-Regulates β-Defensin-2 Expression in Human Airway Epithelium via JAK and NF-κB Signaling Pathways
Kao, C.-Y., Chen, Y., Thai, P., Wachi, S., Huang, F., Kim, C., Harper, R. W., & Wu, R. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.5.3482 · Cited by 424
Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80.
Lee, S. H., Starkey, P. M., & Gordon, S. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.161.3.475 · Cited by 423 · cited 1×
“The GI tract is a major reservoir of macrophages in the body (37) and have a very distinct phenotype and functional capacity.”
Background
Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo
Clayburgh, D. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24970 · Cited by 419 · cited 2×
“TNF stimulation of enterocytes also leads to phosphorylation of the myosin light chain by myosin light chain kinase (MLCK) (73), which in turn leads to intestinal permeability via cytoskeleton rearrangement and modulation of tight junction protein expression.”
Background
Absence of Epithelial Immunoglobulin a Transport, with Increased Mucosal Leakiness, in Polymeric Immunoglobulin Receptor/Secretory Component–Deficient Mice
Johansen, F., Pekna, M., Norderhaug, I. N., Haneberg, B., Hietala, M. A., Krajči, P., Betsholtz, C., & Brandtzæg, P. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.7.915 · Cited by 417 · cited 1×
“Secretory IgA thus serves as a line of defense against MT by limiting adhesion and entry into the epithelium, thereby facilitating clearance via the fecal stream (13, 14).”
Background
Critical Loss of the Balance between Th17 and T Regulatory Cell Populations in Pathogenic SIV Infection
Favre, D., Lederer, S., Kanwar, B., Ma, Z.-M., Proll, S. C., Kasakow, Z., Mold, J. E., Swainson, L. A., Barbour, J. D., Baskin, C. R., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000295 · Cited by 415
Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge
Knöll, P., Schlaak, J., Uhrig, A., Kempf, P., Büschenfelde, K. M. Z., & Gerken, G. (1995) · Journal of Hepatology · doi:10.1016/0168-8278(95)80433-1 · Cited by 403
Tight junctions as targets of infectious agents
Guttman, J. A., & Finlay, B. B. (2008) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.10.028 · Cited by 398 · cited 1×
“Rotavirus, reovirus, norovirus, adenovirus, and coxsackievirus infections are all associated with disruption of the structural barrier of the GI tract and subsequent increased MT (64, 65).”
Background
Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases.
Sartor, R. B. (1997) · PubMed · Cited by 391
A membrane-permeant peptide that inhibits MLC kinase restores barrier function in in vitro models of intestinal disease
Zolotarevsky, Y., Hecht, G. A., Koutsouris, A., Gonzalez, D. E., Quan, C., Tom, J., Mrsny, R. J., & Turner, J. R. (2002) · Gastroenterology · doi:10.1053/gast.2002.34235 · Cited by 385 · cited 1×
“Consistent with this observation, inhibition of MLCK restores barrier function after TNF treatment and suggests that therapeutic interventions aimed at decreasing MLCK activity may be a promising approach in the treatment of TNF-mediated dysfunction of the structural barrier, as discussed below (74).”
Method
Effect of alcohol consumption on the gut.
Bode, C., & Christian Bode, J. (2003) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/s1521-6918(03)00034-9 · Cited by 379
Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality
Ammori, B., Leeder, P., King, R., Barclay, G., Martin, I., Larvin, M., & Mcmahon, M. (1999) · Journal of Gastrointestinal Surgery · doi:10.1016/s1091-255x(99)80067-5 · Cited by 346
Segmented Filamentous Bacteria Are Indigenous Intestinal Bacteria That Activate Intraepithelial Lymphocytes and Induce MHC Class II Molecules and Fucosyl Asialo GM1 Glycolipids on the Small Intestinal Epithelial Cells in the Ex‐Germ‐Free Mouse
Umesaki, Y., Okada, Y., Matsumoto, S., Imaoka, A., & Setoyama, H. (1995) · Microbiology and Immunology · doi:10.1111/j.1348-0421.1995.tb02242.x · Cited by 346
LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.
Lamping, N., Dettmer, R., Schröder, N. W. J., Pfeil, D., Hallatschek, W., Burger, R., & Schumann, R. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2338 · Cited by 345 · cited 1×
“However, therapeutically increased levels of circulating LBP can be protective against gram-negative septicemia (54).”
Background
Regional specialization in the mucosal immune system: what happens in the microcompartments?
Brandtzæg, P., Bækkevold, E. S., Farstad, I. N., Jahnsen, F. L., Johansen, F., Nilsen, E. M., & Yamanaka, T. (1999) · Immunology Today · doi:10.1016/s0167-5699(98)01413-3 · Cited by 342 · cited 23×
“Defense Against MT in the Systemic Circulation As discussed above, in order to access the systemic circulation, microbial antigens that originate in the GI tract must pass through the luminal mucus and IgA, traverse the tight epithelial barrier, escape uptake by GI tract lamina propria macrophages, and then avoid live…”
BackgroundInfluential
Inﬂammatory bowel disease
Teitelbaum, D. H., & Coran, A. G. (2006) · CRC Press eBooks · doi:10.1201/b13237-67 · Cited by 341
Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease.
Cooke, K. R., Hill, G. R., Crawford, J. M., Bungard, D., Brinson, Y. S., Delmonte, J., & Ferrara, J. L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4285 · Cited by 336
Probiotics inhibit nuclear factor-κB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition
Petrof, E. O., Kojima, K., Ropeleski, M. J., Musch, M. W., Tao, Y., Simone, C. D., & Chang, E. B. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.09.001 · Cited by 330
Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children
De Palma, G., Nadal, I., Medina, M., Donat, E., Ribes-Koninckx, C., Calabuig, M., & Sanz, Y. (2010) · BMC Microbiology · doi:10.1186/1471-2180-10-63 · Cited by 330 · cited 1×
“Previous studies have implicated an altered balance in the composition of the microbiota (dysbiosis) in many diseases, such as obesity (16, 17), celiac disease (18), type 2 diabetes (19), atopic eczema (20, 21), asthma (22), inflammatory bowel disease (IBD) (23, 24), and chronic diarrhea (25).”
Background
Intestinal Macrophages Lack CD14 and CD89 and Consequently Are Down-Regulated for LPS- and IgA-Mediated Activities
Smith, P. D., Smythies, L. E., Mosteller‐Barnum, M., Sibley, D. A., Russell, M. W., Merger, M., Sellers, M. T., Orenstein, J. M., Shimada, T., Graham, M. F., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.5.2651 · Cited by 327
C(−260)→T Polymorphism in the Promoter of the CD14 Monocyte Receptor Gene as a Risk Factor for Myocardial Infarction
Hubacek, J. A., Pitha, J. V., Škodová, Z., Stanĕk, V., & Poledne, R. (1999) · Circulation · doi:10.1161/01.cir.99.25.3218 · Cited by 327
The host–microbe interface within the gut
Shanahan, F. (2002) · Best Practice & Research Clinical Gastroenterology · doi:10.1053/bega.2002.0342 · Cited by 308
Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection
Sandler, N. G., Koh, C., Roque, A., Eccleston, J. L., Siegel, R. B., Demino, M., Kleiner, D. E., Deeks, S. G., Liang, T. J., Heller, T., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.063 · Cited by 307
Self-citation
Jejunal microflora in patients with chronic alcohol abuse.
Jc, B., Bode, C., Heidelbach, R., Hk, D., & Ga, M. (1984) · PubMed · Cited by 303
Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy
Marchetti, G. C., Bellistrì, G. M., Borghi, E., Tincati, C., Ferramosca, S., Francesca, M. L., Morace, G., Gori, A., & Monforte, A. D. (2008) · AIDS · doi:10.1097/qad.0b013e3283112d29 · Cited by 296
Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 Infection
Mehandru, S., Poles, M. A., Tenner‐Racz, K., Jean-Pierre, P., Manuelli, V., Lopez, P., Shet, A., Low, A., Mohri, H., Boden, D., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030484 · Cited by 287
Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor–induced toxicity and experimental colitis
Vereecke, L., Sze, M., Guire, C. M., Rogiers, B., Chu, Y., Schmidt‐Supprian, M., Pasparakis, M., Beyaert, R., & Loo, G. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092474 · Cited by 283 · cited 2×
“Moreover, tissue-specific disruption of A20 expression within GI tract enterocytes renders them exquisitely sensitive to TNF-induced toxicity and experimental colitis (75).”
Background
Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C
Balagopal, A., Philp, F. H., Astemborski, J. A., Block, T. M., Mehta, A. S., Long, R. E., Kirk, G. D., Mehta, S. H., Cox, A. L., Thomas, D. L., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.022 · Cited by 282
Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells
Lochner, M., Ohnmacht, C., Presley, L. L., Bruhns, P., Si‐Tahar, M., Sawa, S., & Eberl, G. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20100052 · Cited by 274 · cited 2×
“In these mice, containment of the luminal microbiota requires the generation of abnormally large numbers of tertiary lymphoid tissues (86).”
Background
Paneth cell differentiation in the developing intestine of normal and transgenic mice.
Bry, L., Falk, P., Huttner, K. M., Ouellette, A. J., Midtvedt, T., & Gordon, J. I. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10335 · Cited by 273 · cited 1×
“There are four major types of GI tract epithelial cells (32): absorptive enterocytes; mucin-producing goblet cells; enteroendocrine cells, which produce peptide hormones (33); and Paneth cells, which secrete antimicrobial defensins, digestive enzymes, and growth factors (34).”
Background
Lipopolysaccharide-Binding Protein Plasma Levels and Liver TNF-Alpha Gene Expression in Obese Patients: Evidence for the Potential Role of Endotoxin in the Pathogenesis of Non-Alcoholic Steatohepatitis
Guerra-Ruiz, A. R., Casafont, F., Crespo, J., Cayón, A., Mayorga, M. M., Estébanez, Á., Fernández-Escalante, J. C., & Pons‐Romero, F. (2007) · Obesity Surgery · doi:10.1007/s11695-007-9243-7 · Cited by 268
Modulatory effects of sCD14 and LBP on LPS-host cell interactions
Kitchens, R. L., & Thompson, P. A. (2005) · Journal of Endotoxin Research · doi:10.1179/096805105x46565 · Cited by 268
Differentiation and self-renewal in the mouse gastrointestinal epithelium
Gordon, J. I., & Hermiston, M. L. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90047-7 · Cited by 258 · cited 1×
“Enterocytes are short-lived cells, and the entire mouse GI epithelium is renewed every 3–4 days (35).”
Background
Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection
Arnsten, J. H., Freeman, R., Howard, A. A., Floris-Moore, M., Lo, Y., & Klein, R. S. (2007) · AIDS · doi:10.1097/qad.0b013e3280148c05 · Cited by 252
Tumour necrosis factor α and interleukin 1β in relapse of Crohn's disease
Schreiber, S., Nikolaus, S., Hampe, J., Hämling, J., Koop, I., Groessner, B., Lochs, H., & Raedler, A. (1999) · The Lancet · doi:10.1016/s0140-6736(98)03339-x · Cited by 252
Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection
Guadalupe, M., Sankaran, S., George, M. D., Reay, E., Verhoeven, D. E., Shacklett, B. L., Flamm, J., Wegelin, J. A., Prindiville, T. P., & Dandekar, S. (2006) · Journal of Virology · doi:10.1128/jvi.00120-06 · Cited by 248
Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance
Caradonna, L., Amati, L., Magrone, T., Pellegrino, N. M., Jirillo, E., & Caccavo, D. (2000) · Journal of Endotoxin Research · doi:10.1177/09680519000060030101 · Cited by 247
CD4+ T Cells Mediate Abscess Formation in Intra-abdominal Sepsis by an IL-17-Dependent Mechanism
Chung, D. R., Kasper, D. L., Panzo, R. J., Chtinis, T., Grusby, M. J., Sayegh, M. H., & Tzianabos, A. O. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.1958 · Cited by 246
Predictive Value of Immunologic and Virologic Markers After Long or Short Duration of HIV-1 Infection
Giorgi, J. V., Lyles, R. H., Matud, J. L., Yamashita, T. E., Mellors, J. W., Hultin, L. E., Jamieson, B. D., Margolick, J. B., Rinaldo, C. R., Phair, J., et al. (2002) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200204010-00004 · Cited by 246
Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques
Cecchinato, V., Trindade, C. J., Laurence, A. D. J., Héraud, J., Brenchley, J. M., Ferrari, M. G., Zaffiri, L., Tryniszewska, E. A., Tsai, W. P., Vaccari, M., et al. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.14 · Cited by 244
Self-citation
Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesis
Gori, A., Tincati, C., Rizzardini, G., Torti, C., Quirino, T., Haarman, M., Amor, K. B., van Schaik, J., Vriesema, A. J. M., Knol, J., et al. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01729-07 · Cited by 232 · cited 1×
“Comparative studies of culturable microbiota in human immunodeficiency virus (HIV)-infected and uninfected individuals have shown significant differences between the two, suggesting that the altered microbiota may contribute to HIV disease progression (27).”
Background
Modulatory effects of sCD14 and LBP on LPS-host cell interactions
Kitchens, R. L., & Thompson, P. A. (2005) · Journal of Endotoxin Research · doi:10.1177/09680519050110040701 · Cited by 231 · cited 4×
“sCD14 and LBP both bind LPS and can, at given relative concentrations to one another and LPS, transfer LPS either to high-density lipoproteins (HDLs) to decrease the bioactivity of LPS or to the TLR4/MD-2/CD14 complex on monocytes/macrophages, leading to LPS-mediated stimulation (50).”
BackgroundInfluential
Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease
Pastor, Ó., López–Sanromán, A., Albéniz, E., Martínez, A. D. L. H., Sevillano, E. R., & Albillos, A. (2006) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20019 · Cited by 229 · cited 10×
“In healthy humans these proteins circulate at high concentrations in plasma, reaching the milligram/ liter levels (50, 52). sCD14 and LBP both bind LPS and can, at given relative concentrations to one another and LPS, transfer LPS either to high-density lipoproteins (HDLs) to decrease the bioactivity of LPS or to the…”
BackgroundInfluential
Significance of systemic endotoxaemia in inflammatory bowel disease.
Gardiner, K. R., HALLIDAY, M. I., Barclay, G. R., Milne, L., Brown, D. J., Stephens, S., Maxwell, R., & Rowlands, B. J. (1995) · Gut · doi:10.1136/gut.36.6.897 · Cited by 226 · cited 7×
“Indeed, during the acute phase of infection EndoCAb titers decrease, sCD14 levels increase, and most microbial products found within the lamina propria of the GI tract are within the specialized tissue macrophages described above (52, 126, 139).”
BackgroundInfluential
Intestinal macrophages: unique effector cells of the innate immune system
Smith, P. D., Ochsenbauer‐Jambor, C., & Smythies, L. E. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00288.x · Cited by 225 · cited 1×
“Should microbial products traverse the mucus and epithelial barriers, they are met by a large number of specialized resident macrophages that prevent such products from accessing the systemic circulation (36).”
Background
Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2
Brubaker, P. L., & Anini, Y. (2003) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y03-107 · Cited by 223
Persistent Microbial Translocation and Immune Activation in HIV‐1–Infected South Africans Receiving Combination Antiretroviral Therapy
Cassol, E., Malfeld, S., Mahasha, P. W., der Merwe, V., Cassol, S. A., Seebregts, C. J., Alfano, M., Poli, G., & Rossouw, T. M. (2010) · The Journal of Infectious Diseases · doi:10.1086/655229 · Cited by 218
Dietary Composition and Nonalcoholic Fatty Liver Disease
Solga, S. F., Alkhuraishe, A. R., Clark, J. M., TORBENSON, M., Greenwald, A., Diehl, A. M., & Magnuson, T. H. (2004) · Digestive Diseases and Sciences · doi:10.1023/b:ddas.0000043367.69470.b7 · Cited by 214
Role of the faecal stream in the maintenance of Crohn's colitis.
Harper, P. H., Lee, E. C., Kettlewell, M. G. W., Bennett, M. K., & Jewell, D. P. (1985) · Gut · doi:10.1136/gut.26.3.279 · Cited by 202 · cited 1×
“Additionally, altered composition of the GI tract microbiota has also been suggested to play a role in IBD pathogenesis (99, 100), as revealed by mouse models of IBD in which inflammation is significantly reduced when the mice are housed in germ-free conditions (101, 102).”
Background
Constitutive activation of Rho proteins by CNF-1 influences tight junction structure and epithelial barrier function
Hopkins, A. M., Walsh, S. V., Verkade, P., Boquet, P., & Nusrat, A. (2003) · Journal of Cell Science · doi:10.1242/jcs.00300 · Cited by 202
Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1
Wu, Z., Nybom, P., & Magnusson, K.-E. (2000) · Cellular Microbiology · doi:10.1046/j.1462-5822.2000.00025.x · Cited by 195
Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses
Macal, M., Sankaran, S., Chun, T.-W., Reay, E., Flamm, J., Prindiville, T., & Dandekar, S. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.35 · Cited by 195
Modulation of tight junction structure and function by cytokines
Walsh, S. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00048-x · Cited by 188 · cited 1×
“Indeed, it has been suggested that the ability of inflammatory cytokines to increase paracellular permeability allows neutrophil migration across epithelial barriers to combat invasive pathogens directly (69).”
Background
Biostructure of Fecal Microbiota in Healthy Subjects and Patients With Chronic Idiopathic Diarrhea
Swidsinski, A., Loening–Baucke, V., Verstraelen, H., Osowska, S., & Doerffel, Y. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.04.017 · Cited by 178
Structural and functional changes of the duodenum in human norovirus infection
Troeger, H., Loddenkemper, C., Schneider, T., Schreier, E., Epple, H.-J., Zeitz, M., Fromm, M., & Schulzke, J.-D. (2008) · Gut · doi:10.1136/gut.2008.160150 · Cited by 175 · cited 1×
“Rotavirus, reovirus, norovirus, adenovirus, and coxsackievirus infections are all associated with disruption of the structural barrier of the GI tract and subsequent increased MT (64, 65).”
Background
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Authors: Brenchley, J. M., & Douek, D. C.
Affiliations: National Institutes of Health (US)
ORCID: Brenchley, Jason M.
Douek, Daniel C.
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2012-04-23
Volume: 30
Issue: 1
Pages: 149-173
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-020711-075001
PMC: PMC3513328
OpenAlex: W2146488133
Cited by: 496
References: 222
Citations by year: 2026: 22 · 2025: 32 · 2024: 42 · 2023: 30 · 2022: 44 · 2021: 33 · 2020: 42 · 2019: 59 · 2018: 24 · 2017: 40 · 2016: 34 · 2015: 20 · 2014: 27 · 2013: 32 · 2012: 15
FWCI: 2.74
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (Z01AI001029, ZIAAI005034)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: microbial translocation, gut microbiota, gastrointestinal tract, host-microbe interactions, immune activation, systemic inflammation, therapeutic interventions
MeSH terms: Animals, Anti-Infective Agents, Digestive System Diseases, Humans, Immunologic Factors, Probiotics, Gastrointestinal Tract, Host-Pathogen Interactions, Metagenome

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Microbial Translocation Across the GI Tract

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