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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Helminth Mediated Attenuation of Systemic Inflammation and Microbial Translocation in Helminth-Diabetes Comorbidity
Rajamanickam, A., Munisankar, S., Menon, P. A., Dolla, C., Nutman, T. B., & Babu, S. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00431 · Cited by 15
“intestinal dysbiosis and is associated with increased intestinal permeability and translocation of microbial products into the circulation (Brenchley and Douek, 2012; Levy et al., 2017).”
Background
Common flora and intestine
Wang, K., & Karin, M. (2013) · Cellular Logistics · doi:10.4161/cl.24975 · Cited by 17
“Dysregulated junctional function and translocation of microbes is seen in multiple human diseases, including IBD, HIV infection, and alcohol abuse.(6) Ablation of JAM-A, a component of tight junction complex, resulted in enhanced colonic permeability and inflammation in mice.”
Background
Lipopolysaccharide-Induced Cellular Activation May Participate in the Immunopathogenesis of Visceral Leishmaniasis Alone or in HIV Coinfection
Santos-Oliveira, J. R., & Da‐Cruz, A. M. (2012) · International Journal of Microbiology · doi:10.1155/2012/364534 · Cited by 14
“Recently, Brenchley and Douek [23] reviewed all the restrictions that humans developed to protect themselves from intestinal microbiota translocation.”
Background
Translocation of microbes and changes of immunocytes in the gut of rapid‐ and slow‐progressor Chinese rhesus macaques infected with SIV mac239
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Differential regulation of TREM2 and CSF1R in CNS macrophages in an SIV/macaque model of HIV CNS disease
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The Adenosine Pathway and Human Immunodeficiency Virus-Associated Inflammation
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Host–pathogen interaction in HIV infection
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Distinct compositions and functions of circulating microbial DNA in the peripheral blood compared to fecal microbial DNA in healthy individuals
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“The prevailing hypothesis on microbial or cmDNA transloca tion to the bloodstream involves increased intestinal permeability (22).”
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Probiotics in hospitalized adult patients: a systematic review of economic evaluations
Lau, V. I., Rochwerg, B. N., Xie, F., Johnstone, J., Basmaji, J., Balakumaran, J., Iansavitchene, A., & Cook, D. J. (2019) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/s12630-019-01525-2 · Cited by 13
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Background
Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome
Uhde, M., Indart, A. C., Green, P. H. R., Yolken, R. H., Cook, D. B., Shukla, S. K., Vernon, S. D., & Alaedini, A. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100627 · Cited by 13
“Translocated circulating LPS can result in the rapid secretion of LBP by gastrointestinal and hepatic epithelial cells, as well as sCD14 by CD14 monocytes/macrophages (Brenchley and Douek, 2012).”
Background
Aging With Grace for People Living With HIV: Strategies to Overcome Leaky Gut and Cytomegalovirus Coinfection
Routy, J., Royston, L., & Isnard, S. (2022) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000002838 · Cited by 13
Fisiologia da Barreira Epitelial Intestinal
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Immune Response to an Acute Moderate Dose of Alcohol in Healthy Young Adults
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“the unphysiological movement of gut microbes into systemic circulation, is a source of chronic immune activation and inflammation in numerous diseases (Brenchley and Douek, 2012).”
Background
Immunoinflammatory responses in gastrointestinal tract injury and recovery.
Verma, G., Marella, A., Shaquiquzzaman, M., & Alam, M. M. (2013) · Acta Biochimica Polonica · doi:10.18388/abp.2013_1964 · Cited by 12
“The lumen of the gastrointestinal tract is home to an enormous number of bacterial species, and our microbiota generally thrives in a symbiotic relationship with the host (Brenchley & Douek, 2012).”
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Savanna Monkeys
Turner, T. R., Schmitt, C. A., & Cramer, J. D. (2019) · Cambridge University Press eBooks · doi:10.1017/9781139019941 · Cited by 18
I’ve looked at gut from both sides now: Gastrointestinal tract involvement in the pathogenesis of SARS-CoV-2 and HIV/SIV infections
Pandrea, I., Brooks, K., Desai, R. P., Tare, M., Brenchley, J. M., & Apetrei, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.899559 · Cited by 11
“However, this phenomenon is not specific to SIV/HIV infection, and occurs in multiple clinical conditions in which mucosal epithelium is altered and gut permeability is increased (17).”
BackgroundSelf-citation
The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation
Moreno, E., Ron, R., & Villar, S. S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1072655 · Cited by 11
Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients
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Modeling aging in HIV infection in nonhuman primates to address an emerging challenge of the post-ART era
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“Increased intestinal permeability is associated with a variety of gastrointestinal disorders resulting from perturbation of intestinal epithelial homeostasis [1, 2], these include inflammation, chronic diarrhea [3] and Irritable Bowel Syndrome (IBS) [4, 5].”
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Dissemination of non-typhoidal Salmonella during Plasmodium chabaudi infection affects anti-malarial immunity
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Association of Plasma Soluble Vascular Cell Adhesion Molecule-1 and sCD14 With Mortality in HIV-1–Infected West African Adults With High CD4 Counts
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The Prevention of Viral Infections: The Role of Intestinal Microbiota and Nutritional Factors
Altomare, A., Giovanetti, M., Baldaro, F., Ciccozzi, M., Cicala, M., & Guarino, M. P. L. (2024) · Nutrients · doi:10.3390/nu16152445 · Cited by 12
“This approach not only helps in managing infections like those caused by respiratory and gastrointestinal viruses but also in preventing severe outcomes following infections [19].”
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Deciphering the influence of gut and oral microbiomes on menopause for healthy aging
Yu, S., Huang, F., Huang, Y., Yan, F., Li, L., Xu, S., Zhao, Y., Zhang, X., Chen, R., Chen, X., et al. (2024) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2024.11.010 · Cited by 11
Functional Gastrointestinal Disorders and Childhood Obesity: The Role of Diet and Its Impact on Microbiota
Calcaterra, V., Cena, H., Loperfido, F., Porri, D., Basilico, S., Gazzola, C., Rizzo, C. R., Conti, M. V., Luppino, G., Wasniewska, M. G., et al. (2024) · Nutrients · doi:10.3390/nu17010123 · Cited by 13
“Individuals with IBD have elevated levels of circulating proinflammatory mediators and this systemic inflammation has been suggested to be due to MT because elevated serum levels of LPS, bacterial DNA and LBP can be detected [41–48].”
Possible Crosstalk and Alterations in Gut Bacteriome and Virome in HIV-1 Infection and the Associated Comorbidities Related to Metabolic Disorder
Shrivastav, K., Nasser, H., Ikeda, T., & Nema, V. (2025) · Viruses · doi:10.3390/v17070990 · Cited by 10
“Indeed, such a damaged intestinal epithelial barrier is a major contributor of HIV-1-associated local and systemic inflammation [12,13] (Figure 1).”
Gut and mesenteric lymph node involvement in pediatric patients infected with human immunodeficiency virus
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Serum LPS Associated with Hantavirus and Dengue Disease Severity in Barbados
Douglas, K. O., Samuels, T. A., & Hilaire, M. G.-S. (2019) · Viruses · doi:10.3390/v11090838 · Cited by 10
“Human immunodeficiency virus (HIV) also targets monocytes and high endotoxin levels are associated with HIV replication in the GALT due to MT [45,46].”
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Novel dietary and pharmacologic approaches for acid–base modulation to preserve kidney function and manage uremia
Goraya, N., & Wesson, D. E. (2019) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000568 · Cited by 10
“Gut dysbiosis is associated with increased gut permeability to gut toxins [60,69,70] thereby allowing”
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Effects of Bacterial Translocation and Autophagy on Acute Lung Injury Induced by Severe Acute Pancreatitis
Wang, H., Li, C., Jiang, Y., Li, H., & Zhang, D. (2020) · Gastroenterology Research and Practice · doi:10.1155/2020/8953453 · Cited by 10
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Tradition to Pathogenesis: A Novel Hypothesis for Elucidating the Pathogenesis of Diseases Based on the Traditional Use of Medicinal Plants
Kuchta, K., & Cameron, S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.705077 · Cited by 10
Macaque Paneth Cells Express Lymphoid Chemokine CXCL13 and Other Antimicrobial Peptides Not Previously Described as Expressed in Intestinal Crypts
Lucero, C. M., Junecko, B. A. F., Klamar-Blain, C., Sciullo, L. A., Berendam, S. J., Cillo, A. R., Qin, S., Sui, Y., Sanghavi, S., Murphey‐Corb, M., et al. (2013) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00651-12 · Cited by 10
“Since both of these effects could impact intestinal epithelial barrier integrity, extrapolating to HIV-1-infected individuals, outcomes might include increased microbial translocation and systemic immune activation (40).”
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Presence of Inflammatory Group I and III Innate Lymphoid Cells in the Colon of Simian Immunodeficiency Virus-Infected Rhesus Macaques
Cogswell, A. C., Ferguson, N., & Barker, E. (2020) · Journal of Virology · doi:10.1128/jvi.01914-19 · Cited by 10
“Eventually, the microbial products wind up in circulation (53).”
Background
Microbial Translocation and Infectious Diseases: What Is the Link?
d’Ettorre, G., Douek, D. C., Paiardini, M., Ceccarelli, G., & Vullo, V. (2012) · International Journal of Microbiology · doi:10.1155/2012/356981 · Cited by 10
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Intrathecal Anti-Akkermansia muciniphila IgG Responses in Multiple Sclerosis Patients Linked to CSF Immune Cells and Disease Activity
Cruciani, C., Mathé, C., Puthenparampil, M., Ojer, P. T., Docampo, M. J., Opfer, R., Jelčić, I., Nicot, A. B., Laplaud, D. A., Martinꝉ, R., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14165771 · Cited by 9
Heightened Microbial Translocation Is a Prognostic Biomarker of Recurrent Tuberculosis
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T cell activation is insufficient to drive SIV disease progression
Apetrei, C., Gaufin, T., Brocca‐Cofano, E., Sivanandham, R., Sette, P., He, T., Sivanandham, S., Sosa, N. M., Martin, K. J., Raehtz, K. D., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.161111 · Cited by 9
“vate innate and adaptive immune responses in HIV/SIV infections (12), the causative relationship between intestinal dysfunction and HIV/SIV disease progression has never been proved.”
So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research
Kleinman, A. J., Pandrea, I., & Apetrei, C. (2022) · Viruses · doi:10.3390/v14010135 · Cited by 11
Small Extracellular Vesicles: Key Forces Mediating the Development and Metastasis of Colorectal Cancer
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“The highly permeable intestinal mucosal barrier is connected by tight junctions, avoiding direct contact between the intestinal microbiota and immune cells [74,75].”
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Exploring the Complex Relationship Between Microbiota and Systemic Lupus Erythematosus
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The impact of long-term moderate and heavy alcohol consumption on incident atherosclerosis among persons living with HIV
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“While low level consumption of alcohol may have favorable lipid or antithrombotic effects, low levels of alcohol use have been shown to increase systemic inflammation, as well as risk for microbial translocation (Brenchley and Douek, 2012).”
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From Gut to Blood: Redistribution of Zonulin in People Living with HIV
Augustin, M., Horn, C., Ercanoglu, M. S., Bondet, V., de Silva, U. S., Suárez, I., Chon, S., Nierhoff, D., Zoufaly, A., Wenisch, C., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12102316 · Cited by 8
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In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion
Olwenyi, O. A., Asingura, B., Naluyima, P., Anywar, G., Nalunga, J., Nakabuye, M., Semwogerere, M., Bagaya, B. S., Cham, F., Tindikahwa, A., et al. (2021) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-021-03288-0 · Cited by 9
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Fiuza, J. A., Colt, S., de Ornellas, L. G., Matoso, L. F., Gazzinelli, A., Friedman, J. F., & Corrêa‐Oliveira, R. (2022) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0010837 · Cited by 8
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Savanna Monkeys: The Genus Chlorocebus
Turner, T. R., Schmitt, C. A., & Cramer, J. D. (2019) · Cited by 8
Biomarkers of Cellular Stress Do Not Associate with sCD14 in Progressive HIV and SIV Infections in Vivo
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Overt IL-32 isoform expression at intestinal level during HIV-1 infection is negatively regulated by IL-17A
Gabriel, E. M., Salinas, T. R. W., Gosselin, A., Larouche-Anctil, E., Durand, M., LANDAY, A. L., Far, M. E., Tremblay, C. L., Routy, J., & Ancuța, P. (2021) · AIDS · doi:10.1097/qad.0000000000002972 · Cited by 8
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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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