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Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine. J Surg Res 2017 10;218:35-42

Date

10/08/2017

Pubmed ID

28985873

DOI

10.1016/j.jss.2017.03.049

Scopus ID

2-s2.0-85020395721   14 Citations

Abstract

BACKGROUND: Intestinal alkaline phosphatase (IAP) has been shown to help maintain intestinal homeostasis. Decreased expression of IAP has been linked with pediatric intestinal diseases associated with bacterial overgrowth and subsequent inflammation. We hypothesize that the absence of IAP leads to dysbiosis, with increased inflammation and permeability of the newborn intestine.

METHODS: Sprague-Dawley heterozygote IAP cross-matches were bred. Pups were dam fed ad lib and euthanized at weaning. The microbiotas of terminal ileum (TI) and colon was determined by quantitative real-time polymerase chain reaction (qRT-PCR) of subphylum-specific bacterial 16S ribosomal RNA. RT-PCR was performed on TI for inflammatory cytokines. Intestinal permeability was quantified by fluorescein isothiocyanate-dextran permeability and bacterial translocation by qRT-PCR for bacterial 16S ribosomal RNA in mesenteric lymph nodes. Statistical analysis was done by chi-square analysis.

RESULTS: All three genotypes had similar concentrations of bacteria in the TI and colon. However, IAP knockout (IAP-KO) had significantly decreased diversity of bacterial species in their colonic stool compared with heterozygous and wild-type (WT). IAP-KO pups had a nonstatistically significant 3.9-fold increased inducible nitric oxide synthase messenger RNA expression compared with WT (IAP-KO, 3.92 ± 1.36; WT, 1.0 ± 0.27; P = 0.03). IAP-KO also had significantly increased bacterial translocation to mesenteric lymph nodes occurred in IAP-KO (IAP-KO, 7625 RFU/g ± 3469; WT, 4957 RFU/g ± 1552; P = 0.04). Furthermore, IAP-KO had increased permeability (IAP-KO, 0.297 mg/mL ± 0.2; WT, 0.189 mg/mL ± 0.15 P = 0.07), but was not statistically significant.

CONCLUSIONS: Deficiency of IAP in the newborn intestine is associated with dysbiosis and increased inflammation, permeability, and bacterial translocation.

Author List

Fawley J, Koehler S, Cabrera S, Lam V, Fredrich K, Hessner M, Salzman N, Gourlay D

Authors

Susanne M. Cabrera MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Nita H. Salzman MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Bacterial Translocation
Biomarkers
Colon
Dysbiosis
Ileum
Isoenzymes
Mice, Knockout
Permeability
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction