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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Langat, R., Chakrawarti, A., & Klatt, N. R. (2025) · Current HIV/AIDS Reports · doi:10.1007/s11904-025-00729-0 · Cited by 3
“HIV infection disrupts gut homeostasis by depleting CD4 + T cells in the gastrointestinal (GI) tract, leading to microbial dysbiosis and weakening the gut barrier [46].”
Behavioral Ecology of Savanna Monkeys
Turner, T. R., Schmitt, C. A., & Cramer, J. D. (2019) · Cambridge University Press eBooks · doi:10.1017/9781139019941.009 · Cited by 3
Many Fences Make Better Neighbors
Zemp, F. J., Waterhouse, C. C. M., & Kubes, P. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009391 · Cited by 3
“Commensal microbial translocation and bacteremia as a result of gut mucosal barrier dysfunction is seen in a variety of liver pathologies including viral hepatitis, severe alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) (2).”
BackgroundInfluential
Regulatory T cell abundance and activation status before and after priming with HIVIS-DNA and boosting with MVA-HIV/rgp140/GLA-AF may impact the magnitude of the vaccine-induced immune responses
Chissumba, R. M., Luciano, A., Namalango, E., Bauer, A. P., Bhatt, N., Wahrén, B., Nilsson, C., Geldmacher, C., Scarlatti, G., Jani, I. V., et al. (2018) · Immunobiology · doi:10.1016/j.imbio.2018.08.006 · Cited by 3
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“HIV infection itself is also associated with chronic systemic inflammation, characterized by elevated levels of inflammatory markers, including CRP, and increased microbial translocation leading to higher circulating LPS concentrations [23, 24, 25].”
Influential
The female microbiome in HIV prevention, pathogenesis, and treatment
Peters, B. A., Usyk, M., & Burk, R. D. (2025) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000986 · Cited by 2
Aerobactin is a key driver of hypervirulent Klebsiella pneumoniae translocation and virulence
Hernandez, G. E., Valencia‐Bacca, J. D., Bennett, E., Islam, M. M., Maiti, S., Nutter, N. A., Young, T. M., Caudell, D. L., Costa-Terryll, A., Skelly, J. J., et al. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014122 · Cited by 4
“While mechanistic studies have revealed the involvement of host and bacterial factors in the translocation of enteric pathogens [14,15], the underlying mechanisms remain poorly defined and require further investigation.”
Overview on Lymphatic Filariasis in South Asia
Rajamanickam, A., & Babu, S. (2017) · Neglected tropical diseases · doi:10.1007/978-3-319-68493-2_5 · Cited by 2
Antibiotic Drug Resistance in HIV Seropositive Pregnant Women
Ako-Nai, K. A., & Omo-Omorodion, B. I. (2019) · American journal of microbiological research · doi:10.12691/ajmr-7-2-2 · Cited by 2
“HIV has also been shown to be associated with microbiome shift and immune activation that may affect the outcome of disease progression [7] Antibiotics have been considered the standard treatment of most infections caused by bacteria.”
Background
Potential Role of Microbiota in the Prevention and Therapeutic Management of Infectious Diseases
Shahid, A., Nasir, K., Aslam, S., Kamran, M., Sarfraz, M. H., Saleem, H. G. M., & Khurshid, M. (2022) · Pakistan Journal of Biochemistry and Biotechnology · doi:10.52700/pjbb.v3i1.75 · Cited by 3
“Whenever there is a disruption in the colonization of gut mucosa it results in the translocation of gut microbiota which causes inflammation [33].”
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Immune profiling in Puerto Rican injection drug users with and without HIV-1 infection
Bennett, S. J., Davila, C. A., Reyes, Z., Valentín-Acevedo, A., Carrasco, K. G., Abadie, R., Marlin, M. C., Beel, M., Chapple, A. G., Fernando, S. C., et al. (2023) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiad045 · Cited by 2
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Nemphos, S. M., Green, H. C., Prusak, J. E., Fell, S. L., Goff, K. A., Varnado, M., Didier, K., Guy, N., Moström, M. J., Tatum, C., et al. (2024) · Viruses · doi:10.3390/v16071036 · Cited by 2
Role of aspirin on colorectal cancer risk and bacterial translocation to bloodstream
Mignozzi, S., Pinto, G. D., Guglielmetti, S., Riso, P., Cintolo, M., Penagini, R., Gargari, G., Marino, M., Ciafardini, C., Ferraroni, M., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0319750 · Cited by 2
“Aspirin, CRC and bacterial translocation Necrosis Factor α (TNF-α) and Interleukin-8 levels [25], and this can alter immune response to microbial invasion and also in terms of bacterial selectivity [26].”
Circulating bacterial DNA in cardiovascular disease
Appleby, S. L., & Purcell, R. V. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1476165 · Cited by 2
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Monnig, M. A., Lamb, P. S., Clark, S. E., & Monti, P. M. (2025) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70106 · Cited by 2
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Associations Between Subclass Profile of IgG Response to Gluten and the Gastrointestinal and Motor Symptoms in Children With Cerebral Palsy
Stenberg, R., Uhde, M., Ajamian, M., Green, P. H., Myléus, A., & Alaedini, A. (2021) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003181 · Cited by 2
“Increased intestinal permeability has been shown to be associated with microbial translocation, leading to enhanced systemic immune reactivity to microbial and dietary antigens, including gluten (22,43).”
Background
Role of Microbiota in Health and Disease
Ahmed, M. M., Farhan, M. S., Hamad, A. A., & Edan, A. I. (2022) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2022.00810 · Cited by 2
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Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHUChronically Infected Chinese Rhesus Macaque
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“As previously reported, the translocation of LPS contributes to the systemic immune activation in HIV-1 infection [33], and microbial translocation (especially LPS) has been associated with HIV disease progression [34, 35].”
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Biological Resources for Genomic Investigation in the Vervet Monkey (Chlorocebus)
Jasinska, A. J. (2019) · Cambridge University Press eBooks · doi:10.1017/9781139019941.002 · Cited by 3
Contribution ofSchistosoma mansonito systemic inflammation and microbial translocation among people with HIV in Zambia
Furch, B. D., Mwakamui, S., Sianongo, S., Zyambo, K., Heimburger, D. C., Koethe, J. R., & Kelly, P. M. (2021) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1093/trstmh/trab103 · Cited by 1
Case report: A case report and literature review on spontaneous bacterial peritonitis induced by intestinal barrier damage in a colorectal cancer patient with malnutrition
Xu, P., Shi, S., Yu, Z., Li, D., & Zhang, C. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1444149 · Cited by 1
“BT characterizes the translocation of intestinal microbes and their products from the intestinal lumen to sterile sites, including circulating blood, mesenteric lymph nodes, abdominal cavity, and internal organs (21).”
Biomarkers of environmental enteric dysfunction and neurodevelopmental outcomes among children in rural Bangladesh and Kenya: a prospective cohort study
Ho, G. G., Achando, B. S., Ali, S., Hemlock, C., Pitchik, H. O., Stewart, C. P., Tofail, F., Rahman, M. Z., Alauddin, M., Rao, G., et al. (2025) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2025.05.034 · Cited by 1
“This translocation can lead to immune activation, potentially triggering systemic in ﬂ am-mation, which, in turn, may divert much-needed resources away from child neurodevelopment [48,50].”
Impact of COVID-19 pandemic on toxinogenic Clostridioides difficile infections and correlation with multidrug-resistant bacterial infections
Torrini, L., Diaco, F., Viscido, A., Sacco, F., Sfara, G., Compagnino, D. E., Puggioni, G., Coletti, M., Antonelli, G., & Raponi, G. (2025) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2025.117014 · Cited by 1
Bidirectional interplay between gut and liver in inflammatory bowel disease and hepatobiliary conditions
Abdulla, A. H., Sheikhnoor, A., Ferrao, K., Stiles, L. I., & Mehta, K. J. (2026) · Clinical and Experimental Medicine · doi:10.1007/s10238-026-02102-w · Cited by 1
“This may result in alco - hol-induced microbial translocation [ 154 , 155 ] which could worsen the inflammation in IBD, given that microbial trans - location plays a major role in IBD pathogenesis [160, 161].”
Inflammaging and the role of micronutrients as immunomodulators: a pathway to healthy aging
Tan, S. S. L., Garg, V., Dhiman, A., Bansal, N., & Conway, P. L. (2026) · Immunity & Ageing · doi:10.1186/s12979-026-00569-5 · Cited by 1
“Combined with elevated oxidative stress, these changes significantly increase intestinal permeability and lead to increased translocation of microbial products such as peptidoglycans, lipopolysaccharides (LPS), and flagel-lins into systemic circulation [87].”
Decoding the power of the microbiome in human health
Kumar, M., Almohannadi, N., & Khodor, S. A. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1877371 · Cited by 1
Life History of Savanna Monkeys
Turner, T. R., Schmitt, C. A., & Cramer, J. D. (2019) · Cambridge University Press eBooks · doi:10.1017/9781139019941.014 · Cited by 1
Gut Microbiota in Health and Disease - An Overview
Shrihari, T. G. (2018) · Gastroenterology Medicine & Research · doi:10.31031/gmr.2018.02.000531 · Cited by 1
“Microbiome interventions aimed at restoring the homeostasis of the gut microbiome have recently emerged, such as the ingestion of specific fibers or therapeutic microbes [30,31].”
Background
Intestinal permeability in participants with thermal injury: A case series from a prospective, longitudinal study (HESTIA)
Tipple, C., Moiemen, N. S., Ioannou, C., Paglione, M. G., Goodson, S. G., McGee, K. C., O’Neil, D. M., Winder, C. L., Barnett, C., Wolf, A. I., et al. (2020) · Burns Open · doi:10.1016/j.burnso.2020.05.005 · Cited by 1
Influence of antibiotic therapy on indicators of endotoxinemia and systemic inflammation in acute SARS-CoV-2 lung damage
Yatskov, I. A., Beloglazov, V. A., Kubyshkin, A. V., Nikolaeva, A. P., Александровна, Ш. Н., Zyablitskaya, E. Y., Kunitskaya, Y. E., & Lavrenchuk, N. E. (2022) · Бюллетень Восточно-Сибирского научного центра Сибирского отделения Российской академии медицинских наук · doi:10.29413/abs.2022-7.1.2 · Cited by 1
Antimicrobial and cytotoxic extractives from Ficus sycomorus L. (Moraceae)
Mandou, V. S. M., Tsopgni, W. D. T., Nsangou, M. F., Happi, G. M., Waffo, A. F. K., & Happi, E. N. (2022) · Natural Resources for Human Health · doi:10.53365/nrfhh/155330 · Cited by 1
Association Between Left Ventricular Diastolic Dysfunction, Systemic Inflammation, and Gastrointestinal Symptoms in HIV-Positive Patients on Antiretroviral Therapy
Suba, M.-I., Hogea, B. G., Abu-Awwad, A., Lăzureanu, V. E., Roșca, O., Gurguş, D., Laitin, S. M. D., & Abu-Awwad, S.-A. (2024) · Diseases · doi:10.3390/diseases12120313 · Cited by 1
Ethnoprimatology and Savanna Monkeys
Turner, T. R., Schmitt, C. A., & Cramer, J. D. (2019) · Cambridge University Press eBooks · doi:10.1017/9781139019941.019 · Cited by 1
Depression is associated with decreased severity and lower mortality in non-elderly hospitalized adults with influenza in the United States
Wiemken, T. L. (2020) · The University of Louisville Journal of Respiratory Infections · doi:10.18297/jri/vol4/iss2/1 · Cited by 1
“[46-48] If gut microbiota induced systemic inflammation can trigger mood disorders, modulation of the gut microbiota may play a role in depression therapy and prevention of infection.”
Background
Molecular triggers of non-celiac wheat sensitivity
Alaedini, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821594-4.00010-4 · Cited by 1
Immunodeficiency and the GI Tract
Mehandru, S. (2014) · doi:10.1002/9781118932759.ch26 · Cited by 1
Avaliação da participação dos mircro-organismos da classe Mollicutes na microbiota intestinal de mulheres eutróficas e obesas.
Santos, V. M. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2016.tde-24022016-110550 · Cited by 1
Hepatitis B virus-associated hepatocellular carcinoma in South Africa: epidemiology and impact of HIV-1 co-infection and immune dysregulation
Maponga, T. G. (2016) · SUNScholar (Stellenbosch University) · Cited by 1
Gut IgA Enhances Systemic IgG Responses to Pneumococcal Vaccines Through the Commensal MicrobiotaPreprint
Gutzeit, C., Grasset, E. K., Matthews, D. B., Maglione, P. J., Magri, G., Britton, G. J., Tomalin, L. E., Pybus, M., Vaquero, S. T., Veeramreddy, P. K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.29.439534 · Cited by 1
“This finding was associated with that of augmented circulating sCD14, a soluble antigen released by myeloid cells as a result of hyperactivation by translocated gut bacteria antigens (Brenchley and Douek, 2012; Fadlallah et al., 2018).”
Background
IgA deficiency destabilizes immunological homeostasis towards intestinal microbiota and increases the risk of systemic immune dysregulationPreprint
Conrey, P. E., Denu, L., O’Boyle, K. C., Green, J., Maslanka, J. R., Lubin, J., Duranova, T., Haltzman, B. L., Gianchetti, L., Oldridge, D. A., et al. (2021) · medRxiv · doi:10.1101/2021.08.20.21261620 · Cited by 1
“We investigated the integrity of intestinal barrier function by measuring a widely used marker of intestinal barrier dysfunction and bacterial translocation, the serum concentration of soluble CD14 (sCD14)(Brenchley and Douek, 2012).”
BackgroundMethod
Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered InflammationPreprint
Giron, L. B., Peluso, M. J., Ding, J., Kenny, G., Zilberstein, N., Koshy, J., Hong, K. Y., Rasmussen, H. E., Miller, G., Bishehsari, F., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.12.488051 · Cited by 1
Direct Implications between Prenatal Alcohol Consumption and Gut Microbiome in the Neurodevelopment of Mice Offspring – Focusing On Foetal Alcoholic Spectrum DisordersPreprint
Pedroso-Roussado, C., Guppy, F. M., Bowler, L. D., & Inácio, J. (2022) · Preprints.org · doi:10.20944/preprints202212.0205.v1
The Demographic and Geographic Variations Mediate Fecal and Oral Microbial Dynamics Alteration in Human Population of District FaisalabadPreprint
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The Effect of the TyG Index on Liver Steatosis, Immune Activation, Oxidative Stress, Liver Fibrosis Pathways and Liver Fibrosis in the Miami Adult Studies on HIV (MASH) Cohort
Teeman, C. S. (2021) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fidc010264 · Cited by 1
The accuracy, sensitivity and specificity of rapid point-of-care testing for CD4+ T cell count enumeration and TB diagnosis.
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Monocytes in chronic HIV-1 infection : changes in phenotypic marker expression and their relationship with immune activation
Poovan, K. (2014) · SUNScholar (Stellenbosch University)
Gut immunopathology in response to Vibrio parahaemolyticus infection
Read, K. A. (2025) · Library, Museums and Press - UDSpace (University of Delaware) · doi:10.58088/p41c-5x29

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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