University of Oulu

Lassenius, M. I., Fogarty, C. L., Blaut, M., Haimila, K., Riittinen, L., … Paju, A. (2017). Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes. Journal of Internal Medicine, 281(6), 586–600. https://doi.org/10.1111/joim.12607

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease : a putative role in type 1 diabetes

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Author: Lassenius, M. I.1,2,3; Fogarty, C. L.1,2,3; Blaut, M.4;
Organizations: 1Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
2Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland
4Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam‐Rehbruecke, Nuthetal, Germany
5Blood Group Unit, Finnish Red Cross Blood Service, Helsinki, Finland
6Helsinki University Central Hospital, HUSLAB, Helsinki, Finland
7Department of Bacteriology, HUSLAB, Helsinki, Finland
8Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
9Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
10Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden
11Medical Microbiology and Immunology, Unit of Biomedicine, University of Oulu, Oulu, Finland
12Medical Research Center, Nordlab Oulu University Hospital and University of Oulu, Oulu, Finland
13Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland
14Baker IDI Heart & Diabetes Institute, Melbourne, Vic, Australia
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019082926059
Language: English
Published: John Wiley & Sons, 2017
Publish Date: 2019-08-29
Description:

Abstract

Background: Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high‐fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes.

Methods: Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short‐chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high‐fat diet for 11 weeks.

Results: Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly.

Conclusion: Deprivation of protective intestinal factors may increase the risk of inflammation in the gut – a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation‐driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.

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Series: Journal of internal medicine
ISSN: 0954-6820
ISSN-E: 1365-2796
ISSN-L: 0954-6820
Volume: 281
Issue: 6
Pages: 586 - 600
DOI: 10.1111/joim.12607
OADOI: https://oadoi.org/10.1111/joim.12607
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: This research was supported by The Folkhälsan Research Foundation (PHG), The Wilhelm and Else Stockmann Foundation (PHG, MIL, ML, CF), Liv och Hälsa Foundation (PHG, MIL, CF), Waldemar von Frenckells Foundation (MIL), Kyllikki and Uolevi Lehikoinen Foundation (MIL), Svenska Kulturfonden (MIL), Academy of Finland (PHG, MJ, PJP), Diabetes Research Foundation (MIL, ML), The Novo Nordisk Foundation (#NNF14SA0003 to PHG, ML), Sigrid Juselius Foundation (SH, PJP), Finnish Foundation for Cardiovascular Research (SH), Helsinki University Hospital Research Foundation (PHG,TS) and Karolinska Institutet, Sweden (TS).
Copyright information: © 2017 The Association for the Publication of the Journal of Internal Medicine. This is the peer reviewed version of the following article: Lassenius, M. I., Fogarty, C. L., Blaut, M., Haimila, K., Riittinen, L., … Paju, A. (2017). Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes. Journal of Internal Medicine, 281(6), 586–600. https://doi.org/10.1111/joim.12607, which has been published in final form at https://doi.org/10.1111/joim.12607. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.