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Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment
Open accessAbstract
A fat-enriched diet modifies intestinal microbiota and initiates a low-grade inflammation, insulin resistance and type-2 diabetes. Here, we demonstrate that before the onset of diabetes, after only one week of a high-fat diet (HFD), live commensal intestinal bacteria are present in large numbers in the adipose tissue and the blood where they can induce inflammation. This translocation is prevented in mice lacking the microbial pattern recognition receptors Nod1 or CD14, but overtly increased in Myd88 knockout and ob/ob mouse. This 'metabolic bacteremia' is characterized by an increased co-localization with dendritic cells from the intestinal lamina propria and by an augmented intestinal mucosal adherence of non-pathogenic Escherichia coli. The bacterial translocation process from intestine towards tissue can be reversed by six weeks of treatment with the probiotic strain Bifidobacterium animalis subsp. lactis 420, which improves the animals' overall inflammatory and metabolic status. Altogether, these data demonstrate that the early onset of HFD-induced hyperglycemia is characterized by an increased bacterial translocation from intestine towards tissues, fuelling a continuous metabolic bacteremia, which could represent new therapeutic targets.
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Citations
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
The gut microbiota as an environmental factor that regulates fat storage
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407076101 · Cited by 6,245
Obesity alters gut microbial ecology
Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504978102 · Cited by 6,176
Host-Bacterial Mutualism in the Human Intestine
Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1104816 · Cited by 5,277
Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008) · Diabetes · doi:10.2337/db07-1403 · Cited by 4,819
Self-citationInflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine
Ley, R. E., Peterson, D. A., & Gordon, J. I. (2006) · Cell · doi:10.1016/j.cell.2006.02.017 · Cited by 3,358
Cited by
Functional interactions between the gut microbiota and host metabolism
Tremaroli, V., & Bäckhed, F. (2012) · Nature · doi:10.1038/nature11552 · Cited by 4,387
Inflammatory mechanisms linking obesity and metabolic disease
Saltiel, A. R., & Olefsky, J. M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92035 · Cited by 2,212
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Intestinal permeability – a new target for disease prevention and therapy
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755
The intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089
Impacts of gut bacteria on human health and diseases
Zhang, Y.-J., Li, S., Gan, R.-Y., Zhou, T., Xu, D.-P., & Li, H.-B. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16047493 · Cited by 1,055
“since glucose intolerance was moderately blunted, and insulin sensitivity and fasting hyperinsulinemia were completely normalized [89].”
BackgroundNext-Generation Beneficial Microbes: The Case of Akkermansia muciniphila
Cani, P. D., & de Vos, W. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01765 · Cited by 1,058
Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P. D., & Bäckhed, F. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.026 · Cited by 960
Microbiota and diabetes: an evolving relationship
Tilg, H., & Moschen, A. R. (2014) · Gut · doi:10.1136/gutjnl-2014-306928 · Cited by 853
Tremaroli, V., Karlsson, F., Werling, M., Ståhlman, M., Kovatcheva-Datchary, P., Olbers, T., Fändriks, L., le Roux, C. W., Nielsen, J., & Bäckhed, F. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.009 · Cited by 757
The gut microbiome: connecting spatial organization to function
Tropini, C., Earle, K. A., Huang, K. C., & Sonnenburg, J. L. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.03.010 · Cited by 685
Role of intestinal microbiota and metabolites on gut homeostasis and human diseases
Lin, L., & Zhang, J. (2017) · BMC Immunology · doi:10.1186/s12865-016-0187-3 · Cited by 731
Regulation of metabolism by the innate immune system
Lackey, D. E., & Olefsky, J. M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.189 · Cited by 667
NOD proteins: regulators of inflammation in health and disease
Philpott, D. J., Sorbara, M. T., Robertson, S. J., Croitoru, K., & Girardin, S. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3565 · Cited by 668
Lam, Y. Y., Ha, C. W. Y., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034233 · Cited by 604
“However, the recent report of bacterial translocation into the mesenteric fat of HFD mice [63] and of elevated circulating endotoxin levels in animal models of dietinduced obesity [12] and in obese and type 2 diabetic patients related to insulin resistance [64,65] are consistent with our hypothesized role of the gut i…”
BackgroundThe gut microbiota, obesity and insulin resistance
Shen, J., Obin, M. S., & Zhao, L. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.11.001 · Cited by 599
Verdam, F. J., Fuentes, S., de Jonge, C., Zoetendal, E. G., Erbil, R., Greve, J. W., Buurman, W. A., de Vos, W. M., & Rensen, S. S. (2013) · Obesity · doi:10.1002/oby.20466 · Cited by 587
Gut microbiota, obesity and diabetes
Patterson, E., Ryan, P. M., Cryan, J. F., Dinan, T. G., Ross, R. P., Fitzgerald, G. F., & Stanton, C. (2016) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2015-133285 · Cited by 552
Clark, R. I., Salazar, A., Yamada, R., Fitz-Gibbon, S., Morselli, M., Alcaraz, J., Rana, A., Rera, M., Pellegrini, M., Ja, W. W., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.004 · Cited by 510
Gut microbiota and metabolic syndrome
Festi, D., Schiumerini, R., Eusebi, L. H., Marasco, G., Taddia, M., & Colecchia, A. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i43.16079 · Cited by 534
The role of the microbiome in NAFLD and NASH
Kolodziejczyk, A. A., Zheng, D., Shibolet, O., & Elinav, E. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809302 · Cited by 523
Gut microbiome and liver diseases
Tilg, H., Cani, P. D., & Mayer, E. A. (2016) · Gut · doi:10.1136/gutjnl-2016-312729 · Cited by 525
Can probiotics modulate human disease by impacting intestinal barrier function?
Bron, P. A., Kleerebezem, M., Brummer, R.-J., Cani, P. D., Mercenier, A., MacDonald, T. T., Garcia-Ródenas, C. L., & Wells, J. M. (2017) · British Journal Of Nutrition · doi:10.1017/s0007114516004037 · Cited by 499
“lactis 420, which not only normalised inflammation status but also corrected insulin sensitivity and hyperinsulinemia((117)).”
BackgroundNutritional psychiatry: The present state of the evidence
Marx, W., Moseley, G., Berk, M., & Jacka, F. (2017) · Proceedings of the Nutrition Society · doi:10.1017/s0029665117002026 · Cited by 469
Metabolically healthy versus metabolically unhealthy obesity
Iacobini, C., Pugliese, G., Blasetti Fantauzzi, C., Federici, M., & Menini, S. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.009 · Cited by 453
Fight them or feed them: How the intestinal mucus layer manages the gut microbiota
Schroeder, B. O. (2019) · Gastroenterology report · doi:10.1093/gastro/goy052 · Cited by 464
Aron-Wisnewsky, J., Warmbrunn, M. V., Nieuwdorp, M., & Clément, K. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.057 · Cited by 452
Kong, L.-C., Tap, J., Aron-Wisnewsky, J., Pelloux, V., Basdevant, A., Bouillot, J.-L., Zucker, J.-D., Doré, J., & Clément, K. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.058743 · Cited by 416
Gut microbiota, probiotics and diabetes
Gomes, A. C., Bueno, A. A., de Souza, R. G. M., & Mota, J. F. (2014) · Nutrition Journal · doi:10.1186/1475-2891-13-60 · Cited by 363
Jayashree, B., Bibin, Y. S., Prabhu, D., Shanthirani, C. S., Gokulakrishnan, K., Lakshmi, B. S., Mohan, V., & Balasubramanyam, M. (2014) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1911-4 · Cited by 353
Noble, E. E., Hsu, T. M., & Kanoski, S. E. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00009 · Cited by 333
The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease
Garidou, L., Pomié, C., Klopp, P., Waget, A., Charpentier, J., Aloulou, M., Giry, A., Serino, M., Stenman, L., Lahtinen, S., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.001 · Cited by 303
Self-citationSpecific Gut Microbiome Signature Predicts the Early-Stage Lung Cancer
Zheng, Y., Fang, Z., Xue, Y., Zhang, J., Zhu, J., Gao, R., Yao, S., Ye, Y., Wang, S., Lin, C., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1737487 · Cited by 301
Microbiota regulation of the mammalian gut-brain axis
Burokas, A., Moloney, R. D., Dinan, T. G., & Cryan, J. F. (2015) · Advances in applied microbiology · doi:10.1016/bs.aambs.2015.02.001 · Cited by 300
From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators
Han, H., Yi, B., Zhong, R., Wang, M., Zhang, S., Ma, J., Yin, Y., Yin, J., Chen, L., & Zhang, H. (2021) · Microbiome · doi:10.1186/s40168-021-01093-y · Cited by 292
Microbial modulation of insulin sensitivity
Khan, M. T., Nieuwdorp, M., & Bäckhed, F. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.006 · Cited by 260
Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice
Bagarolli, R. A., Tobar, N., Oliveira, A. G., Araújo, T. G., Carvalho, B. M., Rocha, G. Z., Vecina, J. F., Calisto, K., Guadagnini, D., Prada, P. O., et al. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.08.006 · Cited by 266
Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases?
Brahe, L. K., Astrup, A., & Larsen, L. H. (2013) · Obesity Reviews · doi:10.1111/obr.12068 · Cited by 264
Impact of Diet Composition on Blood Glucose Regulation
Russell, W. R., Baka, A., Björck, I., Delzenne, N., Gao, D., Griffiths, H. R., Hadjilucas, E., Juvonen, K., Lahtinen, S., Lansink, M., et al. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.792772 · Cited by 255
Self-citationModulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet
Candela, M., Biagi, E., Soverini, M., Consolandi, C., Quercia, S., Severgnini, M., Peano, C., Turroni, S., Rampelli, S., Pozzilli, P., et al. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516001045 · Cited by 260
Lelouvier, B., Servant, F., Païssé, S., Brunet, A., Benyahya, S., Serino, M., Valle, C., Ortiz, M. R., Puig, J., Courtney, M., et al. (2016) · Hepatology · doi:10.1002/hep.28829 · Cited by 242
Self-citationLinking the Microbiota, Chronic Disease, and the Immune System
Hand, T. W., Vujkovic-Cvijin, I., Ridaura, V. K., & Belkaid, Y. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.08.003 · Cited by 247
Lenoir, M., Martín, R., Torres-Maravilla, E., Chadi, S., González-Dávila, P., Sokol, H., Langella, P., Chain, F., & Bermúdez-Humarán, L. G. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1826748 · Cited by 245
Self-citationLam, Y. Y., Ha, C. W. Y., Hoffmann, J. M. A., Oscarsson, J., Dinudom, A., Mather, T. J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., et al. (2015) · Obesity · doi:10.1002/oby.21122 · Cited by 223
Endotoxemia—menace, marker, or mistake?
Munford, R. S. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ru0316-151r · Cited by 219
Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes
Massier, L., Chakaroun, R., Tabei, S., Crane, A., Didt, K. D., Fallmann, J., von Bergen, M., Haange, S.-B., Heyne, H., Stumvoll, M., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-320118 · Cited by 194
Causality of small and large intestinal microbiota in weight regulation and insulin resistance
Scheithauer, T. P. M., Dallinga-Thie, G. M., de Vos, W. M., Nieuwdorp, M., & van Raalte, D. H. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.002 · Cited by 188
“After phagocytosis, the DCs disseminated into mesenteric lymph nodes (MLN) and mesenteric adipose tissue (MAT) inducing an inflammatory response similar to LPS [132].”
BackgroundPatterson, E., Ryan, P. M., Wiley, N., Carafa, I., Sherwin, E., Moloney, G., Franciosi, E., Mandal, R., Wishart, D. S., Tuohy, K., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-51781-x · Cited by 168
Stenman, L. K., Lehtinen, M. J., Meland, N., Christensen, J. E., Yeung, N., Saarinen, M. T., Courtney, M., Burcelin, R., Lähdeaho, M.-L., Linros, J., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.10.036 · Cited by 177
Self-citationTrimethylamine N‐oxide: breathe new life
Subramaniam, S., & Fletcher, C. (2018) · British Journal of Pharmacology · doi:10.1111/bph.13959 · Cited by 171
Gut microbiota interacts with brain microstructure and function
Fernandez-Real, J.-M., Serino, M., Blasco, G., Puig, J., Daunis-i-Estadella, J., Ricart, W., Burcelin, R., Fernández-Aranda, F., & Portero-Otin, M. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3076 · Cited by 167
Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health
Ha, C. W. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i44.16498 · Cited by 137
Meli, R., Mattace Raso, G., & Calignano, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00177 · Cited by 137
Rajkumar, H., Kumar, M., Das, N., Kumar, S. N., Challa, H. R., & Nagpal, R. (2015) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248414555004 · Cited by 128
Probiotics supplementation and insulin resistance: A systematic review
Salles, B. I. M., Cioffi, D., & Ferreira, S. R. G. (2020) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-020-00603-6 · Cited by 114
Lin, Y., Bai, M., Wang, S., Chen, L., Li, Z., Li, C., Cao, P., & Chen, Y. (2022) · Diabetes · doi:10.2337/db21-0535 · Cited by 99
Immunological contributions to adipose tissue homeostasis
DiSpirito, J. R., & Mathis, D. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.10.005 · Cited by 88
“It has been reported that obese humans and HFD-fed rodents have circulating LPS levels that are two-to-three fold higher than that of their lean counterparts, a phenomenon termed “metabolic endotoxemia” (however, these LPS levels are still 10–50fold below those measured during a bacterial infection [87,88].”
Chan, K. L., Tam, T. H., Boroumand, P., Prescott, D., Costford, S. R., Escalante, N. K., Fine, N., Tu, Y., Robertson, S. J., Prabaharan, D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.027 · Cited by 88
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013) · Gut Pathogens · doi:10.1186/1757-4749-5-4 · Cited by 84
Zhang, Q., Pan, Y., Zeng, B., Zheng, X., Wang, H., Shen, X., Li, H., Jiang, Q., Zhao, J., Meng, Z.-X., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0190-3 · Cited by 73
Kim, M., Kim, M., Kang, M., Yoo, H. J., Kim, M. S., Ahn, Y.-T., Sim, J.-H., Jee, S. H., & Lee, J. H. (2017) · Food & Function · doi:10.1039/c6fo00993j · Cited by 67
Air Pollution, Early Life Microbiome, and Development
Vallès, Y., & Francino, M. P. (2018) · Current Environmental Health Reports · doi:10.1007/s40572-018-0215-y · Cited by 65
Weninger, S. N., Herman, C., Meyer, R. K., Beauchemin, E. T., Kangath, A., Lane, A. I., Martinez, T. M., Hasneen, T., Jaramillo, S. A., Lindsey, J., et al. (2023) · Microbiome · doi:10.1186/s40168-023-01590-2 · Cited by 37
Lyte, J. M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00796 · Cited by 35
Organotypic cultures as aging associated disease models
Sanchez, M. M., Bagdasarian, I. A., Darch, W., & Morgan, J. T. (2022) · Aging · doi:10.18632/aging.204361 · Cited by 12
Structure shows that the BIR2 domain of E3 ligase XIAP binds across the RIPK2 kinase dimer interface
Lethier, M., Huard, K., Hons, M., Favier, A., Brutscher, B., Boeri Erba, E., Abbott, D. W., Cusack, S., & Pellegrini, E. (2023) · Life Science Alliance · doi:10.26508/lsa.202201784 · Cited by 11
Caudet, J., Trelis, M., Cifre, S., Tapia, G., Soriano, J. M., Rodrigo, R., & Merino-Torres, J. F. (2022) · Antioxidants · doi:10.3390/antiox11112090 · Cited by 6
Metadata
- Authors
- Amar, J., Chabo, C., Waget, A., Klopp, P., Vachoux, C., Bermúdez‐Humarán, L. G., Smirnova, N., Bergé, M., Sulpice, T., Lahtinen, S., Ouwehand, A., Langella, P., Rautonen, N., Sansonetti, P. J., & Burcelin, R.
- Venue
- EMBO Molecular Medicine
- Published
- 2011-08-03
- Volume
- 3
- Issue
- 9
- Pages
- 559-572
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- OpenAlex
- W2165857119
- Cited by
- 836
- References
- 17
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- gold
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