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Microbial Translocation Across the GI Tract
Open accessAbstract
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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“However, in the absence of infection, endotoxin still crosses the mucosal membranes of gut, gums, nose or lungs, the main source being intestinal permeability [36, 37].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [37]
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The impact of microbiota on PD-1/PD-L1 inhibitor therapy outcomes: A focus on solid tumors
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“Interestingly, gut decontamination of gram-negative bacteria just prior to transplantation reduces the frequency and/or severity of graft versus host disease in experimental models and in humans (Beelen et al., 1992; Brenchley and Douek, 2012; Storb et al., 1983)).”
BackgroundInfluentialNon-coeliac gluten sensitivity: A review of the literature
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“In addition, emerging studies have reported that gut dysbiosis contributes to the disruption in intestinal barrier function in CKD, allowing the translocation of gut-derived toxins, bacterial products, and intact bacteria into the circulation (5, 6).”
Backgroundγδ T Cells Are Involved in Acute HIV Infection and Associated with AIDS Progression
Li, Z., Li, W., Li, N., Jiao, Y., Chen, D., Cui, L., Hu, Y., Wu, H., & He, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106064 · Cited by 35
“IL-17 is thought to be important for maintaining intestinal mucosal integrity and controlling microbial translocation [15].”
BackgroundRajamanickam, A., Munisankar, S., Bhootra, Y., Dolla, C., Nutman, T. B., & Babu, S. (2016) · Infection and Immunity · doi:10.1128/iai.00772-16 · Cited by 37
“LPS and 16S rRNA (common to most bacteria) are often used as indicators of bacterial translocation, and endotoxin core IgG antibody (EndoCAb) is also used as a surrogate marker for the measurement of circulating LPS levels (1, 2).”
BackgroundMethodDuque-Correa, M. A., Karp, N. A., McCarthy, C., Forman, S., Goulding, D., Sankaranarayanan, G., Jenkins, T. P., Reid, A. J., Cambridge, E. L., Ballesteros Reviriego, C., et al. (2019) · PLOS Pathogens · doi:10.1371/journal.ppat.1007265 · Cited by 35
γδ T‐cell responses during HIV infection and antiretroviral therapy
Juno, J. A., & Eriksson, E. M. (2019) · Clinical & Translational Immunology · doi:10.1002/cti2.1069 · Cited by 34
“gut bacteria increases gut permeability and allows translocation of bacterial products into the liver via the portal vein.(139,145,146) Finally, obese individuals also exhibit elevated levels of LPS and other markers of microbial translocation, supporting a putative link between gut permeability, low-grade inflammatio…”
BackgroundThe Emerging Role of Gut Dysbiosis in Cardio-metabolic Risk Factors for Heart Failure
Sata, Y., Marques, F. Z., & Kaye, D. M. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-01046-0 · Cited by 34
Gut Leakage of Fungal‐Related Products: Turning Up the Heat for HIV Infection
Isnard, S., Lin, J. C.-Y., Bu, S., Fombuena, B., Royston, L., & Routy, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.656414 · Cited by 36
“Gut damage and increased gut permeability constitute hallmarks of both acute and chronic phases of HIV infection (1, 2).”
BackgroundDo the Microbiota Influence Vaccines and Protective Immunity to Pathogens?Preprint
Collins, N., & Belkaid, Y. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028860 · Cited by 37
Kelso, N. E., Sheps, D. S., & Cook, R. L. (2015) · The American Journal of Drug and Alcohol Abuse · doi:10.3109/00952990.2015.1058812 · Cited by 34
“Alcohol use alone increases risk for microbial translocation, especially among persons with alcohol use disorders; however, even non-dependent heavy drinkers feature increased GI tract permeability that requires two weeks of abstinence to regain normal epithelial integrity (36).”
BackgroundProgress in Research on Colorectal Cancer-Related Microorganisms and Metabolites
Han, S., Jing, Z., Wu, Y., Wu, W., & Yang, X. (2020) · Cancer Management and Research · doi:10.2147/cmar.s268943 · Cited by 34
“Previous research reported that the intestinal flora has the capacity to defend the body against pathogens by recognizing the conserved antigen of bacteria.(20,21) The intestinal flora was reported to protect the local homeostasis.”
BackgroundThe Role of Mucosal Immunity and Recombinant Probiotics in SARS-CoV2 Vaccine Development
Moradi‐Kalbolandi, S., Majidzadeh‐A, K., Abdolvahab, M. H., Jalili, N., & Farahmand, L. (2021) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-021-09773-9 · Cited by 35
Monnig, M. A. (2016) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2016.1211667 · Cited by 35
“Independently, HIV and alcohol use induce translocation of microbial products from the gastrointestinal tract into systemic circulation (28), leading to immune activation and inflammation.”
Using the Pathogenic and Nonpathogenic Nonhuman Primate Model for Studying Non-AIDS Comorbidities
Pandrea, I., LANDAY, A. L., Wilson, C. C., Stock, J. L., Tracy, R. P., & Apetrei, C. (2015) · Current HIV/AIDS Reports · doi:10.1007/s11904-014-0245-5 · Cited by 32
“Intestinal permeability is also increased in multiple pathogenic conditions, such as inflammatory bowel disease, pancreatitis, graft-versus-host disease, excessive alcohol consumption, as well as obesity and diabetes or with age [25, 22] .”
BackgroundInfluentialJohnstone, J., Heels‐Ansdell, D., Thabane, L., Meade, M. O., Marshall, J., Lauzier, F., Duan, E. H., Zytaruk, N. L., Lamarche, D., Surette, M. G., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-025228 · Cited by 33
Xie, Z., Zhang, G., Liu, R., Wang, Y., Tsapieva, A., Zhang, L., & Han, J. (2023) · Nutrients · doi:10.3390/nu15071758 · Cited by 33
Zeyneloglu, C., Babayev, H., Öğülür, İ., Ardıçlı, S., Pat, Y., Yazıcı, D., Zhao, B., Chang, L., Liu, X., D’Avino, P., et al. (2025) · FEBS Letters · doi:10.1002/1873-3468.70113 · Cited by 36
“…colonization by opportunistic pathogens like S. aureus in AD [213], or facultative pathogens like Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catar-rhalis in respiratory conditions [15,214,215], loss of beneficial commensals, and subsequent bacterial translocation [1,56].”
Bacterial translocation in critical illness
Krentz, T., & Allen, S. J. (2017) · Journal of Small Animal Practice · doi:10.1111/jsap.12626 · Cited by 31
Integrins: Integrating the Biology and Therapy of Cell–cell Interactions
Pandolfi, F., Franza, L., Altamura, S., Mandolini, C., Cianci, R., Ansari, A. A., & Kurnick, J. T. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.11.002 · Cited by 31
Animal-microbial symbioses in changing environments
Carey, H. V., & Duddleston, K. N. (2014) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2014.02.015 · Cited by 31
“…been linked to pathological states such as inflammatory bowel disease and obesity in humans and experimental animals (Lozupone et al., 2012), a situation often exacerbated by increased gut permeability which can compromise the host’s defenses against microbial invasion (Brenchley and Douek, 2012).”
BackgroundMaintaining Poise: Commensal Microbiota Calibrate Interferon Responses
McAleer, J. P., & Kolls, J. K. (2012) · Immunity · doi:10.1016/j.immuni.2012.07.001 · Cited by 31
“In order for this to occur, microbial products must pass through several barriers such as mucus, epithelial tight junctions, liver Kupffer cells, and serum antibodies (Brenchley and Douek, 2012).”
BackgroundShata, M. T. M., Abdel-hameed, E. A., Hetta, . F., & Sherman, K. E. (2013) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2013-201581 · Cited by 31
Raehtz, K. D., Pandrea, I., & Apetrei, C. (2016) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2016.07.006 · Cited by 31
“This, in turn, not only creates more available target cells for the virus, but also functionally exhausts the immune system and its capacity for regeneration (Brenchley and Douek, 2012; Brenchley et al., 2006b, 2006b; Gordon et al., 2007; Pandrea et al., 2007b).”
BackgroundInfluentialA pregnancy complication-dependent change in SIgA-targeted microbiota during third trimester
Cui, M., Qi, C., Yang, L., Zhang, M., Wang, H., She, G., Yu, R., Miao, T., & Sun, J. (2020) · Food & Function · doi:10.1039/c9fo02919b · Cited by 30
The Role of Fermented Dairy Products on Gut Microbiota Composition
Okoniewski, A., Dobrzyńska, M., Kusyk, P., Dziedzic, K., Przysławski, J., & Drzymała-Czyż, S. (2023) · Fermentation · doi:10.3390/fermentation9030231 · Cited by 33
Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis
Colomb, F., Giron, L. B., Trbojević‐Akmačić, I., Lauc, G., & Abdel‐Mohsen, M. (2019) · Current HIV/AIDS Reports · doi:10.1007/s11904-019-00433-w · Cited by 28
Phetsouphanh, C., Xu, Y., & Zaunders, J. J. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00681 · Cited by 27
“However, loss of cells may also be due to chronic immune activation, secondary to chronic exposure to microbial products translocated across epithelial barriers depleted of CD4 T cells during primary HIV-1 infection (39) and alteration of homeostasis due to eventual fibrotic changes to lymphoid tissue (40).”
BackgroundUntersmayr, E., Bax, H. J., Bergmann, C., Bianchini, R., Cozen, W., Gould, H. J., Hartmann, K., Josephs, D. H., Levi‐Schaffer, F., Penichet, M. L., et al. (2019) · Allergy · doi:10.1111/all.13718 · Cited by 27
“Microbial products, especially cell walls of gram‐negative bacteria (lipopolysaccharide [LPS] or endotoxin), are powerful stimulators of innate immunity and of B‐cell activation, resulting in inflammation that can lead to disease states, and even septic shock if present in very high doses.(109) Microbial translocation…”
BackgroundMethodWang, C., Li, Q., Tang, C. X., Zhao, X., He, Q., Tang, X., & Ren, J. (2021) · Immunity Inflammation and Disease · doi:10.1002/iid3.483 · Cited by 27
Tilahun, M., Gedefie, A., Belayhun, C., Sahle, Z., & Abera, A. (2022) · Infection and Drug Resistance · doi:10.2147/idr.s346705 · Cited by 30
“Lactoferrin, which has been demonstrated to be harmful to Giardia trophozoites in vitro, is released continually by the gallbladder.(102) The epithelial cells lining the wall of the intestine respond to Giardia trophozoite contact by production of cytokines and chemokines.”
BackgroundBarriers to HIV remission research in low‐ and middle‐income countries
Rossouw, T. M., Tucker, J. D., van Zyl, G. U., Sikwesi, K., & Godfrey, C. C. (2017) · Journal of the International AIDS Society · doi:10.7448/ias.20.1.21521 · Cited by 29
Gut microbiome supplementation as therapy for metabolic syndrome
Antony, M. A., Chowdhury, A., Edem, D., Raj, R., Nain, P., Joglekar, M., Verma, V. K., & Kant, R. (2023) · World Journal of Diabetes · doi:10.4239/wjd.v14.i10.1502 · Cited by 28
Detection of bacteraemia and host response in healthy neonatal foals
Hackett, E. S., Lunn, D. P., Ferris, R. A., Horohov, D. W., Lappin, M. R., & McCue, P. M. (2014) · Equine Veterinary Journal · doi:10.1111/evj.12307 · Cited by 27
Barbeiro, D. F., Koike, M. K., Coelho, A. M. M., da Silva, F. P., & Machado, M. C. C. (2015) · Pancreatology · doi:10.1016/j.pan.2015.10.012 · Cited by 28
Petschow, B. W., Burnett, B. P., Shaw, A. L., Weaver, E. M., & Klein, G. L. (2014) · Digestive Diseases and Sciences · doi:10.1007/s10620-014-3322-0 · Cited by 26
“, intact bacteria, lipopolysaccharides, food antigens, xenobiotics) with associated release of proinflammatory cytokines and recruitment of inflammatory cells [1, 4, 41] that can further exacerbate mucosal damage and gut permeability [42].”
BackgroundJames, W. A., Ogunrinde, E., Wan, Z., Kamen, D. L., Oates, J. C., Gilkeson, G. S., & Jiang, W. (2022) · The Journal of Rheumatology · doi:10.3899/jrheum.210952 · Cited by 26
Malassezia in Inflammatory Bowel Disease: Accomplice of Evoking Tumorigenesis
Yang, Q., Ouyang, J., Pi, D., Li, F., & Yang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.846469 · Cited by 28
“This tight barrier is obviously a main hurdle which must be broken through for microbial antigens to enter the human body, for example, in the lumen of the gut (54).”
BackgroundEffects of alcohol withdrawal on monocyte subset defects in chronic alcohol users
Donnadieu‐Rigole, H., Mura, T., Portalès, P., Duroux-Richard, I., Bouthier, M., Eliaou, J., Perney, P., & Apparailly, F. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.5a0216-060rr · Cited by 26
“Subjects with an AUD are known to have significantly increased plasma endotoxin levels compared with HCs [6] secondary to the increase in microbial translocation independently on liver disease [7].”
BackgroundDillon, S. M., Guo, K., Austin, G. L., Gianella, S., Engen, P. A., Mutlu, E., Losurdo, J., Swanson, G. R., Chakradeo, P. S., Keshavarzian, A., et al. (2018) · AIDS · doi:10.1097/qad.0000000000001863 · Cited by 23
“The loss of gut Th17 and Th22 cells likely precipitate epithelial barrier breakdown, resulting in the movement of microbes and microbial products into the lamina propria and eventually, the systemic circulation [33,47].”
Oliva, A., Aversano, L., Angelis, M. D., Mascellino, M. T., Miele, M. C., Morelli, S., Battaglia, R., Iera, J., Bruno, G., Corazziari, E. S., et al. (2019) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofz507 · Cited by 26
“Although biomarkers of microbial translocation, inflammation, and intestinal damage have been associated with multiple infective and noninfective diseases [13, 21], their role in CDI or in the pathogenesis of n-BSI after CDI is still unexplored.”
BackgroundPrevention and Treatment of Grade C Postoperative Pancreatic Fistula
Xiang, C., Chen, Y., Liu, X., Zheng, Z., Zhang, H., & Tan, C. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11247516 · Cited by 25
“Bacterial translocation (BT) is the migration of gut microorganisms or their products across the intestinal mucosal barrier into extraintestinal sites such as the mesenteric lymph nodes and the portal system and then into the systemic circulation and the processes of the liver, spleen, lu g, and other organs [33,34].”
BackgroundKumar, N. P., Venkataraman, A., Hanna, L. E., Putlibai, S., Karthick, M. S., Rajamanikam, A., Sadasivam, K., Sundaram, B., & Babu, S. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab279 · Cited by 25
“8 • ofid • Kumar et al in the absence of overt bacteremia [20].”
BackgroundMethodResultInfluentialPreterm Birth in Women With HIV: The Role of the Placenta
Ikumi, N. M., & Matjila, M. J. (2022) · Frontiers in Global Women s Health · doi:10.3389/fgwh.2022.820759 · Cited by 27
“However, this loss may also be attributed to chronic immune inflammation secondary to chronic exposure to microbes translocated across epithelial barriers including the gut and fibrotic change to lymphoid tissue during primary HIV infection (133, 134).”
BackgroundDacrema, M., Ali, A., Ullah, H., Khan, A., Minno, A. D., Xiao, J., Martins, A. M. C., & Daglia, M. (2022) · Cancers · doi:10.3390/cancers14225682 · Cited by 27
Metadata
- Authors
- Brenchley, J. M., & Douek, D. C.
- Affiliations
- National Institutes of Health (US)
- 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
- 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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