A Review of This Enzyme Role in the Intestinal Barrier Function

Funding Information: This study was supported by ERDF through the operation POCI-01-0145-ERDF-007746 funded by Programa Operacional Competitividade e Internacionaliza??o?COMPETE2020 and by National Funds through FCT?Funda??o para a Ci?ncia e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013) and (PTDC/BAA-AGR/7419/2020).Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome. The use of IALP as a possible biomarker to assess intestinal barrier function and strategies to modulate IALP activity are also discussed.publishersversionpublishe

Influence of human milk on very preterms’ gut microbiota and alkaline phosphatase activity

Funding: This study was supported by Milupa DN-ELN 2017 grant from the Portuguese Neonatal Society, by ERDF through the operation POCI-01-0145-ERDF-007746 funded by the Programa Operacional Competitividade e Internacionalização–COMPETE2020, and by National Funds through FCT– Fundação para a Ciência e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013).The FEEDMI Study (NCT03663556) evaluated the influence of infant feeding (mother’s own milk (MOM), donor human milk (DHM) and formula) on the fecal microbiota composition and alkaline phosphatase (ALP) activity in extremely and very preterm infants (≤32 gestational weeks). In this observational study, preterm infants were recruited within the first 24 h after birth. Meconium and fecal samples were collected at four time points (between the 2nd and the 26th postnatal days. Fecal microbiota was analyzed by RT-PCR and by 16S rRNA sequencing. Fecal ALP activity, a proposed specific biomarker of necrotizing enterocolitis (NEC), was evaluated by spectrophotometry at the 26th postnatal day. A total of 389 fecal samples were analyzed from 117 very preterm neonates. Human milk was positively associated with beneficial bacteria, such as Bifidobacterium, Bacteroides ovatus, and Akkermancia muciniphila, as well as bacterial richness. Neonates fed with human milk during the first week of life had increased Bifidobacterium content and fecal ALP activity on the 26th postnatal day. These findings point out the importance of MOM and DHM in the establishment of fecal microbiota on neonates prematurely delivered. Moreover, these results suggest an ALP pathway by which human milk may protect against NEC.publishersversionpublishe

Is gut microbiota the key?

Funding: This study was supported by ERDF through the operation POCI-01-0145-ERDF-007746 funded by Programa Operacional Competitividade e Internacionalização—COMPETE2020 and by National Funds through FCT—Fundação para a Ciência e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013) and CHRC (UIDB/04923/2020 and UIDP/04923/2020). This study was also supported by Emilio Peres grant from the Portuguese Society of Diabetology.The Mediterranean diet (MD) has been recommended for type 2 diabetes (T2D) treatment. The impact of diet in shaping the gut microbiota is well known, particularly for MD. However, the link between MD and diabetes outcome improvement is not completely clear. This study aims to evaluate the role of microbiota modulation by a nonpharmacological intervention in patients with T2D. In this 12-week single-arm pilot study, nine participants received individual nutritional counseling sessions promoting MD. Gut microbiota, biochemical parameters, body composition, and blood pressure were assessed at baseline, 4 weeks, and 12 weeks after the intervention. Adherence to MD [assessed by Mediterranean Diet Adherence Screener (MEDAS) score] increased after the intervention. Bacterial richness increased after 4 weeks of intervention and was negatively correlated with fasting glucose levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Prevotella to Bacteroides ratio also increased after 4 weeks. In contrast, glycated haemoglobin (HbA1c) and HOMA-IR were only decreased at the end of study. Alkaline phosphatase activity was assessed in fecal samples and was negatively correlated with HbA1c and positively correlated with bacterial diversity. The results of this study reinforce that MD adherence results in a better glycemic control in subjects with T2D. Changes in gut bacterial richness caused by MD adherence may be relevant in mediating the metabolic impact of this dietary intervention.publishersversionpublishe

A Randomized, Double-Blind, Controlled Trial

Funding This work was supported by ERDF through the operation POCI-01−0145-ERDF-007746 funded by the Programa Operacional Competitividade e Internacionalização − COMPETE2020 and by FCT - Fundação para a Ciência e a Tecnologia, IP national support through CINTESIS, R&D Unit (UIDB/4255/2020), CHRC (UIDP/04923/2020 and UIDB/04923/2020) and through the project reference PTDC/BAA-AGR/7419/2020.Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. Gut microbiota was analyzed by 16S rRNA gene sequencing. Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass and did not changed significantly serum cardiometabolic biomarkers. Nonalcoholic and alcoholic beer increased gut microbiota diversity which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase activity, a marker of intestinal barrier function. These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.publishersversionpublishe

Empowerment-based nutrition interventions on blood pressure: a randomized comparative effectiveness trial

IntroductionEmpowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program.MethodsThree hundred and eleven adults (median age of 44 years, IQR 34–54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference.ResultsThere were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of −2.5 mm Hg in SBP (95% CI, −4.1 to −0.8) and − 2.7 mm Hg in DBP (95% CI, −3.8 to −1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was −2.1 mm Hg in SBP (95% CI, −3.7 to −0.5) and − 2.3 mm Hg in DBP (95% CI, −3.4 to −1.1). This effect increases in subjects with high-normal BP or hypertension [SBP − 7.9 mm Hg (95% CI, −12.5 to −3.3); DBP − 7.3 mm Hg (95% CI, −10.2 to −4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of −1.5 mm Hg (95% CI, −2.6 to −0.4) in ITT analysis and − 1.4 mm Hg (95% CI, −2.4 to −0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio.ConclusionSalt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction

a randomized comparative effectiveness trial

Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was sponsored by CUF and Pingo Doce, as part of the Menos Sal Portugal project, and with support from the Centro de Medicina Laboratorial Germano de Sousa. The sponsors did not play a role in the study design or the interpretation of the results. The study was also promoted by the CINTESIS@RISE (UIDB/4255/2020 and UIDP/4255/2020), NOVA Medical School of Universidade NOVA de Lisboa and supported by national funds through FCT Fundação para a Ciência e a Tecnologia, I.P., within the scope of the project “RISE-LA/P/0053/2020”. Publisher Copyright: Copyright © 2023 Moreira-Rosário, Ismael, Barreiros-Mota, Morais, Rodrigues, Castela, Mendes, Soares, da Costa, Oliveira, Henriques, Pinto, Pita, de Oliveira, Maciel, Serafim, Araújo, Rocha, Pestana, Silvestre, Marques, Faria, Polonia and Calhau.Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34–54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of −2.5 mm Hg in SBP (95% CI, −4.1 to −0.8) and − 2.7 mm Hg in DBP (95% CI, −3.8 to −1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was −2.1 mm Hg in SBP (95% CI, −3.7 to −0.5) and − 2.3 mm Hg in DBP (95% CI, −3.4 to −1.1). This effect increases in subjects with high-normal BP or hypertension [SBP − 7.9 mm Hg (95% CI, −12.5 to −3.3); DBP − 7.3 mm Hg (95% CI, −10.2 to −4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of −1.5 mm Hg (95% CI, −2.6 to −0.4) in ITT analysis and − 1.4 mm Hg (95% CI, −2.4 to −0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.publishersversionpublishe

IPA and its precursors differently modulate the proliferation, differentiation, and integrity of intestinal epithelial cells

Funding Information: This work was supported by ERDF through the operation POCI-01-0145-ERDF-007746 funded by the Programa Operacional Competitividade e Internacionalização – COMPETE2020 and by FCT - Fundação para a Ciência e a Tecnologia, IP national support through CINTESIS, R&D Unit (UIDB/4255/2020), CHRC (UIDP/04923/2020 and UIDB/04923/2020), through the project reference PTDC/BAA-AGR/7419/2020 and the 2020.06333.BD. Publisher Copyright: © 2023 The Korean Nutrition Society and the Korean Society of Community Nutrition This is an Open Access article distributed.BACKGROUND/OBJECTIVES: Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level. MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/ or 72 h with IPA or its precursors – indole, tryptophan, and propionate – at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation. RESULTS: IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation. CONCLUSIONS: In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure. Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.publishersversionpublishe

Intestinal Alkaline Phosphatase Activity and Efficiency Are Altered in Severe COVID-19 Patients

Background & Aims: Although gut inflammation and dysbiosis have been implicated in the pathophysiology of severe cases of coronavirus disease 2019 (COVID-19), the role of intestinal anti-inflammatory enzymes, such as alkaline phosphatase, is still underexplored. Therefore, the aim of this study was to compare intestinal alkaline phosphatase (iALP) activity and its proinflammatory substrate - bacterial lipopolysaccharide (LPS) - concentration between mild-to-moderate and severe COVID-19 patients. Methods: Stool samples collected from 53 mild-to-moderate and 57 severe adult COVID-19 patients, previously enrolled in a national multicentre cross-sectional study (NCT04355741), were analysed for iALP activity and LPS concentration. Results: iALP activity decreased by 40% in severe compared to mild-to-moderate COVID-19 patients (median [interquartile range] of 120.6 [25.2–593.1] nmol pNP/min/g of protein vs 202.8 [102.1–676.1] nmol pNP/min/g of protein; P = .04) after adjustment for clinical and gut microbiota parameters. Regarding fecal LPS, its concentration was found to be decreased in severe patients (mean ± standard error of mean of 18,118 ± 1225 EU/g of feces vs 22,508 ± 1203 EU/g of feces; P = .01), although this parameter did not correlate with plasma levels of C-reactive protein (P = .08), a sensitive biomarker of systemic inflammation. In contrast, fecal ALP activity / LPS concentration ratio, an indicator of iALP efficiency, was found to be increased in severe compared to mild-to-moderate COVID-19 patients (P = .04). Conclusion: Changes in iALP kinetic parameters found in severe COVID-19 patients may represent a potential mechanism to counterbalance alterations in gut homeostasis (eg inflammation and dysbiosis) associated with COVID-19 severity