title: Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women.
abstract: Increased intestinal permeability with subsequent metabolic endotoxemia, i.e., elevated circulating levels of bacterial lipopolysaccharide, LPS, has been introduced as a novel initiator of obesity related metabolic disturbances in non-pregnant individuals. The objective was to investigate the extent to which intestinal permeability, measured by serum zonulin concentration, is related to metabolic endotoxemia and metabolic risk markers in overweight pregnant women.
  
  
  
  This was a cross-sectional study including 100 pregnant overweight women in early pregnancy. Serum zonulin was analyzed using ELISA, and markers for metabolic endotoxemia (LPS), inflammation (high-sensitive C-reactive protein and glycoprotein acetylation GlyA), glucose metabolism (fasting glucose and insulin), and lipid metabolism were measured.
  
  
  
  Higher serum zonulin concentration associated positively with LPS (P=0.02), inflammatory markers (P<0.001), insulin (P<0.001), insulin resistance (P<0.001), and triglycerides (P=0.001), and negatively with insulin sensitivity (P=0.001) (ANOVA with Tukey's corrections or Kruskal-Wallis nonparametric test with Bonferroni correction for zonulin quartiles). All the observed associations were confirmed (P<0.015) in a linear regression model adjusted with potential confounding factors. Both LPS and GlycA showed positive relationship with insulin resistance, serum insulin, triglycerides, total and LDL-cholesterol and negative relationship with insulin sensitivity (P≤0.03) in the univariate linear regression. Positive relationship was also found between LPS and HDL-cholesterol (P=0.03).
  
  
  
  Our findings suggest that increased serum zonulin concentration, i.e., increased intestinal permeability, contributes to metabolic endotoxemia, systemic inflammation, and insulin resistance in overweight pregnant women. By reinforcing intestinal barrier, it may be possible to manipulate maternal metabolism during pregnancy with subsequent health benefits.
authors.affiliation: Institute of Biomedicine, University of Turku, Finland; Functional Foods Forum, University of Turku, Finland. Electronic address: Kati.Mokkala@utu.fi.
authors.forename: Kati
authors.initials: K
authors.lastname: Mokkala
authors.affiliation: Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Pellonperä
authors.affiliation: Institute of Biomedicine, University of Turku, Finland; Functional Foods Forum, University of Turku, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Röytiö
authors.affiliation: Oral and Maxillofacial Diseases, University of Helsinki and University Hospital of Helsinki, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Pussinen
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Turku and Turku University Hospital, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Rönnemaa
authors.affiliation: Institute of Biomedicine, University of Turku, Finland; Functional Foods Forum, University of Turku, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Laitinen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002772:Cholera Toxin / Q000032:analysis / Q000378:metabolism*; D003430:Cross-Sectional Studies; D019446:Endotoxemia / Q000097:blood; D005260:Female; D005387:Finland / Q000453:epidemiology; D005947:Glucose / Q000378:metabolism; D006242:Haptoglobins; D006801:Humans; D007249:Inflammation / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D050356:Lipid Metabolism; D008659:Metabolic Diseases / Q000453:epidemiology / Q000378:metabolism*; D050177:Overweight / Q000453:epidemiology / Q000378:metabolism*; D010539:Permeability; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000378:metabolism*; D011498:Protein Precursors; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin; D005947:Glucose
keywords: Intestinal permeability; Low grade inflammation; Metabolic endotoxemia; Overweight; Pregnancy