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Systemic exposure to Pseudomonal bacteria: a potential link between type 1 diabetes and chronic inflammation

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Abstract

Bacterial endotoxins have been associated with chronic inflammation and the development and progression of diabetic nephropathy. We hypothesized that subjects with high serum lipopolysaccharide activity also carry remains of bacterial DNA in their system. Serum-derived bacterial DNA clones were isolated and identified from 10 healthy controls and 14 patients with type 1 diabetes (T1D) using universal primers targeted to bacterial 16S rDNA. A total of 240 clones representing 35 unique bacterial species were isolated and identified. A significant proportion of the isolated bacteria could be assigned to our living environment. Proteobacteria was by far the most prevalent phylum among the samples. Notably, the patients had significantly higher frequencies of Stenotrophomonas maltophilia clones in their sera compared to the healthy controls. Real-time PCR analysis of S. maltophilia and Pseudomonas aeruginosa flagellin gene copy number in the human leukocyte DNA fraction revealed that the overall Pseudomonal bacterial load was higher in older patients with T1D. Serum IgA- and IgG-antibody levels against Pseudomonal bacteria Delftia acidovorans, P. aeruginosa, and S. maltophilia were also determined in 200 healthy controls and 200 patients with T1D. The patients had significantly higher serum levels of IgA antibodies against all three Pseudomonal bacteria. Additionally, the IgA antibodies against Pseudomonal bacteria correlated significantly with serum C-reactive protein. These findings indicate that recurrent or chronic Pseudomonal exposure may increase susceptibility to chronic inflammation in patients with T1D.

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Acknowledgments

The study was supported by Folkhälsan Research Foundation (P.-H. G.), Wilhelm and Else Stockmann Foundation (P.-H. G., L. P., C. F., M. L.), Diabetes Research Foundation (M. L.), The Novo Nordisk Foundation (M. L.), and the Sigrid Juselius Foundation (P. J. P.). Part of this study was presented in abstract form at the 45th Annual Meeting of the Scandinavian Society for the Study of Diabetes (2010), Malmö, Sweden. Laboratory technicians and nurses R. Keva, M. Parkkonen, A.-R. Salonen, A. Sandelin, T. Soppela and J. Tuomikangas at the Folkhälsan Institute of Genetics are acknowledged for their skillful technical assistance. We also acknowledge the physicians and nurses at each study center (Supplementary file 5).

Conflict of interest

No potential conflicts of interest relevant to this paper were reported.

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Authors and Affiliations

  1. Biomedicum Helsinki, Folkhälsan Institute of Genetics, Folkhälsan Research Center/FinnDiane, Haartmaninkatu 8, 00290, Helsinki, Finland

    Lina Peräneva, Christopher L. Fogarty, Carol Forsblom, Per-Henrik Groop & Markku Lehto

  2. Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

    Lina Peräneva, Christopher L. Fogarty, Carol Forsblom, Per-Henrik Groop & Markku Lehto

  3. Biomedicum Helsinki, Institute of Dentistry, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland

    Pirkko J. Pussinen

  4. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

    Per-Henrik Groop

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  1. Lina Peräneva
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  2. Christopher L. Fogarty
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  3. Pirkko J. Pussinen
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  4. Carol Forsblom
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Correspondence to Markku Lehto.

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Communicated by Massimo Federici.

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Peräneva, L., Fogarty, C.L., Pussinen, P.J. et al. Systemic exposure to Pseudomonal bacteria: a potential link between type 1 diabetes and chronic inflammation. Acta Diabetol 50, 351–361 (2013). https://doi.org/10.1007/s00592-012-0421-2

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