RESUMO
Alkaline phosphatase (AP) is a ubiquitous membrane-bound glycoprotein that catalyzes phosphate monoesters' hydrolysis from organic compounds, an essential process in cell signaling. Four AP isozymes have been described in humans, placental AP, germ cell AP, tissue nonspecific AP, and intestinal AP (IAP). IAP plays a crucial role in gut microbial homeostasis, nutrient uptake, and local and systemic inflammation, and its dysfunction is associated with persistent inflammatory disorders. AP is a strong predictor of mortality in the general population and patients with cardiovascular and chronic kidney disease (CKD). However, little is known about IAP modulation and its possible consequences in CKD, a disease characterized by gut microbiota imbalance and persistent low-grade inflammation. Mitigating inflammation and dysbiosis can prevent cardiovascular complications in patients with CKD, and monitoring factors such as IAP can be useful for predicting those complications. Here, we review IAP's role and the results of nutritional interventions targeting IAP in experimental models to prevent alterations in the gut microbiota, which could be a possible target of predictive, preventive, personalized medicine (PPPM) to avoid CKD complications. Microbiota and some nutrients may activate IAP, which seems to have a beneficial impact on health; however, data on CKD remains scarce.
RESUMO
Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 -/- mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.
Assuntos
Fosfatase Alcalina/deficiência , Cálcio/metabolismo , Osso Esponjoso/metabolismo , Intestinos/enzimologia , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos , Densidade Óssea , Cálcio/sangue , Duodeno/metabolismo , Feminino , Fraturas do Colo Femoral/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatos/sangueRESUMO
The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.
RESUMO
SCOPE: Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. METHODS AND RESULTS: We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. CONCLUSION: Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption.