title: Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M I
authors.initials: MI
authors.lastname: Lassenius
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: C L
authors.initials: CL
authors.lastname: Fogarty
authors.affiliation: Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Blaut
authors.affiliation: Blood Group Unit, Finnish Red Cross Blood Service, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Haimila
authors.affiliation: Helsinki University Central Hospital, HUSLAB, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Riittinen
authors.affiliation: Helsinki University Central Hospital, HUSLAB, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Paju
authors.affiliation: Department of Bacteriology, HUSLAB, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Kirveskari
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Järvelä
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ahola
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: D
authors.initials: D
authors.lastname: Gordin
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M-A
authors.initials: MA
authors.lastname: Härma
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Hamarneh
authors.affiliation: Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Hodin
authors.affiliation: Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.affiliation: Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Tervahartiala
authors.affiliation: Medical Microbiology and Immunology, Unit of Biomedicine, University of Oulu, Oulu, Finland.|Medical Research Center, Nordlab Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Hörkkö
authors.affiliation: Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Pussinen
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: C
authors.initials: C
authors.lastname: Forsblom
authors.affiliation: Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M-R
authors.initials: MR
authors.lastname: Taskinen
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Baker IDI Heart & Diabetes Institute, Melbourne, Vic, Australia.
authors.forename: P-H
authors.initials: PH
authors.lastname: Groop
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Abdominal Center of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.identifier: 0000-0001-8414-7285
authors.initials: M
authors.lastname: Lehto
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D005232:Fatty Acids, Volatile / Q000032:analysis / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005647:Fucosyltransferases; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology*; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D000469:Alkaline Phosphatase; D015415:Biomarkers; D005232:Fatty Acids, Volatile; D005647:Fucosyltransferases; D007136:Immunoglobulins; D039841:Leukocyte L1 Antigen Complex; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: calprotectin; immunoglobulin A; inflammation; intestinal alkaline phosphatase; short-chain fatty acids; type 1 diabetes