The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Bifidobacteria can protect from enteropathogenic infection through production of acetate
Abstract
The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.
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“Additional support for the role of enteric bacteria in maintaining normal barrier function is provided by data that SCFA (e.g., butyrate and acetate) improve intestinal barrier function (64, 84).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [64]
In the citing paper
“Numerous in vitro studies have demonstrated that bifidobacteria can inhibit pathogens through the production of organic acids (38), antibacterial peptides (39), quorum-sensing inhibitors (40, 41), or immune stimulation (42) among other mechanisms, providing molecular clues of their capacity to prevent certain infections.”
From Bifidobacteria and Their Health-Promoting Effects (2017) · cites this paper as [38]
In the citing paper
“these bacteria have been linked to fortification of the gut mucosal protection through activities against pathogens12, 13.”
From Diet and the Intestinal Microbiome: Associations, Functions, and Implications for Health and Disease (2014) · cites this paper as [13]
In the citing paper
“which have been shown in vitro and in vivo to support the integrity of the intestinal mucosa in a variety of ways (Fukuda et al., 2011; Gaudier et al., 2004; Macia et al., 2015; Willemsen et al., 2003; Wrzosek et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Fukuda et al., 2011
In the citing paper
“Bifidobacterium longum has been shown to protect mice from enterohemorrhagic E. coli O157 infection through the production of SCFAs, that prevent IEC apoptosis and inflammation, thus preserving gut epithelium integrity, and reducing the spread of Stx2 toxin into the bloodstream, ultimately improving host survival [52].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [52]
In the citing paper
“Acetate production was associated with protection against Escherichia coli O157 in mice that were mono-colonized by Bifidobacterium [39].”
From Role of the gut microbiota in nutrient competition and protection against intestinal pathogen colonization (2023) · cites this paper as [39]
Citations
Cites
tRNAscan-SE: A Program for Improved Detection of Transfer RNA Genes in Genomic Sequence
Lowe, T. M., & Eddy, S. R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.5.955 · Cited by 11,200
Summaries of Affymetrix GeneChip probe level data
Irizarry, R. A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng015 · Cited by 4,837
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241
Improved microbial gene identification with GLIMMER
Delcher, A. L. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.23.4636 · Cited by 2,493
Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome
Tarr, P. I., Gordon, C. A., & Chandler, W. L. (2005) · The Lancet · doi:10.1016/s0140-6736(05)71144-2 · Cited by 1,791
Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators
Staels, B., Köenig, W., Habib, A., Merval, R., Lebret, M., Pineda‐Torra, I., Delerive, P., Fadel, A., Chinetti, G., Fruchart, J., et al. (1998) · Nature · doi:10.1038/31701 · Cited by 1,138
Liver X receptors as integrators of metabolic and inflammatory signaling
Zelcer, N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27883 · Cited by 978
Schell, M. A., Karmirantzou, M., Snel, ., Vilanova, D., Berger, B. W., Pessi, G., Zwahlen, M.-C., Desiere, F., Peer Bork, B., Delley, M., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212527599 · Cited by 942
Sela, D. A., Chapman, J., Adeuya, A., Kim, J., Chen, F., Whitehead, T. R., Lapidus, A. L., Rokhsar, D. S., Lebrilla, C. B., German, J. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809584105 · Cited by 895
Tedelind, S., Westberg, F., Kjerrulf, M., & Vidal, A. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i20.2826 · Cited by 880
Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes
Kurokawa, K., Itoh, T., Kuwahara, T., Oshima, K., Toh, H., Toyoda, A., Takami, H., Morita, H., Sharma, V. K., Srivastava, T. P., et al. (2007) · DNA Research · doi:10.1093/dnares/dsm018 · Cited by 869
Self-citationLXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes
Laffitte, B. A., Repa, J. J., Joseph, S. B., Wilpitz, D. C., Kast, H. R., Mangelsdorf, D. J., & Tontonoz, P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.507 · Cited by 683
Review article: bifidobacteria as probiotic agents – physiological effects and clinical benefits
PICARD, C., FIORAMONTI, J., FRANCOIS, A., ROBINSON, T., NEANT, F., & MATUCHANSKY, C. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02615.x · Cited by 618
Gut microbiota: a potential new territory for drug targeting
Jia, W. P., Li, H., Zhao, L., & Nicholson, J. K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2505 · Cited by 478
Genome-scale analyses of health-promoting bacteria: probiogenomics
Ventura, M., O'Flaherty, S., Claesson, M. J., Turroni, F., Klaenhammer, T. R., van Sinderen, D., & O'Toole, P. W. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2047 · Cited by 471
Gervois, P. P., Fruchart, J., Delerive, P., & Staels, B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004045200 · Cited by 459
Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host
Sonnenburg, J. L., Chen, C. T. L., & Gordon, J. I. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040413 · Cited by 423
Garmendia, J., Frankel, G. M., & Crepin, V. F. (2005) · Infection and Immunity · doi:10.1128/iai.73.5.2573-2585.2005 · Cited by 408
Automated Finishing with AutofinishPreprint
Gordon, D., Desmarais, C., & Green, P. (2001) · Genome Research · doi:10.1101/gr.171401 · Cited by 376
The love–hate relationship between bacterial polysaccharides and the host immune system
Mazmanian, S. K., & Kasper, D. L. (2006) · Nature reviews. Immunology · doi:10.1038/nri1956 · Cited by 362
Asahara, T., Shimizu, K., Nomoto, K., Hamabata, T., Ozawa, A., & Takeda, Y. (2004) · Infection and Immunity · doi:10.1128/iai.72.4.2240-2247.2004 · Cited by 277
Mechanisms of probiosis and prebiosis: considerations for enhanced functional foods
Saulnier, D. M. A., Spinler, J. K., Gibson, G. R., & Versalovic, J. A. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.01.002 · Cited by 236
PRIMe: A Web Site That Assembles Tools for Metabolomics and Transcriptomics
Akiyama, K., Chikayama, E., Yuasa, H., Shimada, Y., Tohge, T., Shinozaki, K., Hirai, M. Y., Sakurai, T., Kikuchi, J., & Saito, K. (2008) · In Silico Biology · doi:10.3233/isb-00362 · Cited by 206
Self-citationAnnison, G., Illman, R. J., & Topping, D. L. (2003) · Journal of Nutrition · doi:10.1093/jn/133.11.3523 · Cited by 170
Self-citationSethi, S. M., Ziouzenkova, O., Ni, H., Wagner, D. D., Plutzky, J., & Mayadas, T. N. (2002) · Blood · doi:10.1182/blood-2002-01-0316 · Cited by 166
Complete Genome Sequence of Bifidobacterium longum subsp. longum KACC 91563
Ham, J.-S., Lee, T., Byun, M.-J., Lee, K., Kim, M., Han, G.-S., Jeong, S.-G., Oh, M., Kim, D., & Kim, H. (2011) · Journal of Bacteriology · doi:10.1128/jb.05620-11 · Cited by 143
Stable Isotope Labeling of Arabidopsis thaliana for an NMR-Based Metabolomics Approach
Kikuchi, J., Shinozaki, K., & Hirayama, T. (2004) · Plant and Cell Physiology · doi:10.1093/pcp/pch117 · Cited by 139
Self-citationStatistical Indices for Simultaneous Large-Scale Metabolite Detections for a Single NMR Spectrum
Chikayama, E., Sekiyama, Y., Okamoto, M., Nakanishi, Y., Tsuboi, Y., Akiyama, K., Saito, K., Shinozaki, K., & Kikuchi, J. (2010) · Analytical Chemistry · doi:10.1021/ac9022023 · Cited by 134
Self-citationImprovement of bacterial transformation efficiency using plasmid artificial modification
Yasui, K., Kano, Y., Tanaka, K. Y., Watanabe, K., Shimizu-Kadota, M., Yoshikawa, H., & Suzuki, T. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn884 · Cited by 129
Self-citationShort-Chain Fatty Acids Impact on Intestinal Adaptation, Inflammation, Carcinoma, and Failure
Kles, K. A., & Chang, E. B. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.048 · Cited by 120
Schüller, S., Frankel, G. M., & Phillips, A. D. (2004) · Cellular Microbiology · doi:10.1046/j.1462-5822.2004.00370.x · Cited by 116
Sugar Transport Systems of Bifidobacterium longum NCC2705
Parche, S., Amon, J., Janković, I., Rezzonico, E., Beleut, M., Barutçu, H., Schendel, I., Eddy, M. P., Burkovski, A., Arigoni, F., et al. (2006) · Microbial Physiology · doi:10.1159/000096455 · Cited by 103
A Proteome Reference Map and Proteomic Analysis of Bifidobacterium longum NCC2705
Yuan, J., Zhu, L., Liu, X., Li, T., Zhang, Y., Ying, T., Wang, B., Wang, J., Dong, H., Feng, E., et al. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500410-mcp200 · Cited by 100
Regulation of Complement C3 Expression by the Bile Acid Receptor FXR
Li, J., Pircher, P. C., Schulman, I. G., & Westin, S. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411473200 · Cited by 93
Nakamura, T., Sasaki, T., FUJIMORI, M., Yazawa, K., Kano, Y., Amano, J., & Taniguchi, S. (2002) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.66.2362 · Cited by 91
Hase, K. (2005) · DNA Research · doi:10.1093/dnares/12.2.127 · Cited by 86
Self-citationSekiyama, Y., Chikayama, E., & Kikuchi, J. (2010) · Analytical Chemistry · doi:10.1021/ac9019076 · Cited by 76
Self-citationPathogenesis of Renal Disease Due to Enterohemorrhagic Escherichia coli in Germ-Free Mice
Eaton, K. A., Friedman, D. I., Francis, G. J., Tyler, J. S., Young, V. B., Haeger, J., Abu-Ali, G., & Whittam, T. S. (2008) · Infection and Immunity · doi:10.1128/iai.01626-07 · Cited by 75
Hijikata, A., Kitamura, H., Kimura, Y., Yokoyama, R., Aiba, Y., Bao, Y., Fujita, S., Hase, K., Hori, S., Ishii, Y., et al. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm430 · Cited by 74
Self-citationFukuda, S., Nakanishi, Y., Chikayama, E., Ohno, H., Hino, T., & Kikuchi, J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004893 · Cited by 64
Self-citationActivation-Induced Cytidine Deaminase Deficiency Causes Organ-Specific Autoimmune Disease
Hase, K., Takahashi, D., Ebisawa, M., Kawano, S., Itoh, K., & Ohno, H. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003033 · Cited by 63
Self-citationTop-down Phenomics of Arabidopsis thaliana
Tian, C., Chikayama, E., Tsuboi, Y., Kuromori, T., Shinozaki, K., Kikuchi, J., & Hirayama, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700549200 · Cited by 60
Self-citationGagnon, M., Kheadr, E., Dabour, N., Richard, D., & Fliss, I. (2006) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2006.04.041 · Cited by 52
Yoshimura, K., MATSUI, T., & Itoh, K. (2009) · Antonie van Leeuwenhoek · doi:10.1007/s10482-009-9391-y · Cited by 38
Self-citationMorita, T., TANABE, H., Takahashi, K., & SUGIYAMA, K. (2004) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2003.03208.x · Cited by 37
Antonio, V., Janvier, B., Brouillet, A., Andréani, M., & Raymondjean, M. (2003) · Biochemical Journal · doi:10.1042/bj20030098 · Cited by 32
Enzyme-linked immunosorbent assay to detect Shiga toxin of Shigella dysenteriae and related toxins
Kongmuang, U., Honda, T., & Miwatani, T. (1987) · Journal of Clinical Microbiology · doi:10.1128/jcm.25.1.115-118.1987 · Cited by 28
Daily bowel movements and Escherichia coli O157 infection
Kitajima, H. (2002) · Archives of Disease in Childhood · doi:10.1136/adc.87.4.335 · Cited by 6
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Self-citationDiversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533
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Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413
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Metadata
- Authors
- Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., Taylor, T. D., Itoh, K., Kikuchi, J., Morita, H., Hattori, M., & Ohno, H.
- Affiliations
- RIKEN (JP)
- RIKEN Advanced Science Institute (JP)
- The University of Tokyo (JP)
- The University of Osaka (JP)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Gifu University (JP)
- Azabu University (JP)
- Chiba University (JP)
- Corresponding author
- Hattori, Masahira
- Ohno, Hiroshi
- ORCID
- Venue
- Nature
- Published
- 2011-01
- Volume
- 469
- Issue
- 7331
- Pages
- 543-547
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2045119680
- Cited by
- 2,387
- References
- 48
- Citations by year
- 2026: 138 · 2025: 166 · 2024: 199 · 2023: 161 · 2022: 208 · 2021: 244 · 2020: 199 · 2019: 155 · 2018: 162 · 2017: 155 · 2016: 130 · 2015: 129 · 2014: 121 · 2013: 90 · 2012: 93
- FWCI
- 158.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22689017)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Bifidobacterium longum, acetate, Escherichia coli O157:H7, probiotics, ABC transporters, carbohydrate transport, gut microbiota
- MeSH terms
- Acetates, Animals, Bifidobacterium, Chlorocebus aethiops, Escherichia coli Infections, Molecular Sequence Data, Vero Cells, Genome, Bacterial, Escherichia coli O157, Gene Expression Profiling, Mice
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