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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 pathology1,2,3. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases4,5,6. 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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Figure 1: Effect of preventive and non-preventive bifidobacteria against lethal infection with E. coli O157.
Figure 2: Identification of acetate as causative substance for protection provided by preventive bifidobacteria.
Figure 3: Genomic and metabolic profiling of the bifidobacterial strains.
Figure 4: Functional analysis of the ABC-type carbohydrate transporter.

Accession codes

Primary accessions

GenBank/EMBL/DDBJ

Gene Expression Omnibus

Data deposits

Microarray data have been deposited in the NCBI Gene Expression Omnibus under accession number GSE13061. Sequences for the B. longum genomes have been deposited in the DNA Data Bank of Japan, GenBank and the EMBL Nucleotide Sequence Database under accession numbers AP010888, AP010889, AP010890, AP010891 and AP010892.

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Acknowledgements

We thank H. Kitamura and M. E. Mariotti-Ferrandiz for discussions and for reading the manuscript; T. Morita for suggestions; and C. Nishigaki, M. Ohmae, Y. Chiba, T. Kato, H. Shima, A. Nakano, K. Sakaguchi, K. Furuya, C. Yoshino, H. Inaba, E. Iioka, K. Motomura and Y. Hattori for technical support. This research was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan: a Grant-in-Aid for Scientific Research on Priority Areas ‘Comprehensive Genomics’ (M.H.), ‘Membrane Traffic’ (H.O.) and ‘Matrix of Infectious Phenomena’ (K.H.); Young Scientists (S.F., K.H. and J.K.); Challenging Exploratory Research (J.K.); Scientific Research (H.O.); and Scientific Research on Innovative Areas ‘Intracellular Logistics’ (H.O.). This work was also supported in part by a RIKEN President’s Special Research Grant (J.K.); a RIKEN DRI Research Grant (S.F.); a CREST grant from the Japan Science and Technology Agency (J.K.); the Danone Institute of Japan (H.O.); the Institute for Fermentation, Osaka (S.F.); the Kieikai Research Foundation (S.F.); the Naito Foundation (S.F.); the Nestlé Nutrition Council, Japan (S.F.); the Sasakawa Scientific Research Grant from the Japan Science Society (S.F. and Y.N.); the Yakult Bio-Science Foundation (S.F.); the Academic Frontier Project for Private Universities (Matching Fund Subsidy (H.M.)); and the Private University Scientific Foundation (H.M.).

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Authors

Contributions

S.F., K.I., M.H. and H.O. conceived and designed the experiments. S.F., Y.N., K.H., K.Y., K.O., H.M. and K.I. performed the experiments. S.F., H.T. and Y.N. analysed the data. T.T., J.M.C., D.L.T., T.S., T.D.T., J.K. and M.H. contributed reagents, materials and analysis tools. S.F., H.T., K.H., T.D.T., M.H. and H.O. wrote the paper.

Corresponding authors

Correspondence to Masahira Hattori or Hiroshi Ohno.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-12 with legends and Supplementary Tables 1-12. (PDF 5135 kb)

Supplementary Table 13

This table contains 1H NMR profiling raw data. (XLS 105 kb)

Supplementary Table 14

This table contains 1H-13C correlation NMR profiling raw data. (XLS 89 kb)

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Fukuda, S., Toh, H., Hase, K. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011). https://doi.org/10.1038/nature09646

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