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

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.

Trimethylamine increases intestinal fatty acid absorption: in vitro studies in a Caco-2 cell culture system.

Although elevated blood levels of trimethylamine N-oxide (TMAO) have been associated with atherosclerosis development in humans, the role of its gut microbiota-derived precursor, TMA, in this process has not been yet deciphered. Taking this into account, and the fact that increased intestinal fatty acid absorption contributes to atherosclerosis onset and progression, this study aimed to evaluate the effect of TMA on fatty acid absorption in a cell line that mimics human enterocytes. Caco-2 cells were treated with TMA 250 µM for 24 h. Fatty acid absorption was assessed by measuring the apical-to-basolateral transport and the intracellular levels of BODIPY-C12, a fluorescently labelled fatty acid analogue. Gene expression of the main intestinal fatty acid transporters was evaluated by real-time quantitative reverse transcription PCR. Compared to control conditions, TMA increased, in a time-dependent manner and by 20-50 %, the apical-to-basolateral transport and intracellular levels of BODIPY-C12 fatty acid in Caco-2 cells. Fatty acid transport protein 4 (FATP4) and fatty acid translocase (FAT)/CD36 gene expression were not stimulated by TMA, suggesting that TMA-induced increase in fatty acid transport may be mediated by an increase in FAT/CD36 and/or FATP4 activity and/or fatty acid passive transport. This study demonstrated that TMA increases the intestinal absorption of fatty acids. Future studies are necessary to confirm if this may constitute a novel mechanism that partially explains the existing positive association between the consumption of a diet rich in TMA sources (e.g. red meat) and the increased risk of atherosclerotic diseases.

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

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.

The impact of Hafnia alvei HA4597™ on weight loss and glycaemic control after bariatric surgery - study protocol for a triple-blinded, blocked randomized, 12-month, parallel-group, placebo-controlled clinical trial.

BACKGROUND: Subjects with obesity exhibit changes in gut microbiota composition and function (i.e. dysbiosis) that contribute to metabolic dysfunction, including appetite impairment. Although bariatric surgery is an effective treatment for obesity with a great impact on weight loss, some subjects show weight regain due to increased energy intake after the surgery. This surgery involves gut microbiota changes that promote appetite control, but it seems insufficient to completely restore the obesity-associated dysbiosis - a possible contributor for weight regain. Thus, modulating gut microbiota with probiotics that could improve appetite regulation as a complementary approach to post-operative diet (i.e. Hafnia alvei HA4597™), may accentuate post-surgery weight loss and insulin sensitivity. METHODS: This is a protocol of a triple-blinded, blocked-randomized, parallel-group, placebo-controlled clinical trial designed to determine the effect of Hafnia alvei HA4597™ supplementation on weight loss and glycaemic control 1 year after bariatric surgery. Patients of Hospital CUF Tejo, Lisbon, that undergo Roux-en-Y gastric bypass are invited to participate in this study. Men and women between 18 and 65 years old, with a BMI ≥ 35 kg/m2 and at least one severe obesity-related comorbidity, or with a BMI ≥ 40 kg/m2, and who are willing to take 2 capsules of Hafnia alvei HA4597™ probiotic supplements (equivalent to 5 × 107 CFU) vs. placebo per day for 90 days are included in this study. Assessments are carried out at baseline, 3, 6, 9, and 12 months after the surgery. Loss of weight in excess and glycated haemoglobin are considered primary outcomes. In addition, changes in other metabolic and inflammatory outcomes, gut microbiota composition and metabolites, as well as gastrointestinal quality of life are also being assessed during the trial. DISCUSSION: The evidence obtained in this study will provide relevant information regarding the profile of the intestinal microbiota of individuals with severe obesity and the identification of the risk/benefit ratio of the use of Hafnia alvei HA4597™ as an adjunctive treatment in the maintenance of metabolic and weight control one year after the surgical intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05170867. Registered on 28 December 2021.

Decreased adiponectin/leptin ratio relates to insulin resistance in adults with obesity.

Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the reliability of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4 ± 3.7 kg/m2) (NCT02169778). With the use of a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep, and waist-to-hip ratio (P < 0.001), AdipoQ/Lep being the strongest independent predictor (Beta = -0.449, P < 0.001). A lower AdipoQ/Lep was correlated with higher body mass index (Rs = -0.490, P < 0.001), body fat mass (Rs = -0.486, P < 0.001), waist-to-height ratio (Rs = -0.290, P = 0.037), and plasma resistin (Rs = -0.365, P = 0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.NEW & NOTEWORTHY Adiponectin/leptin ratio, triacylglycerols, and waist-to-hip ratio explained almost half of HOMA-IR variance in the context of obesity. This study provides evidence to support adipose tissue dysfunction as a central feature of the pathophysiology of obesity and insulin resistance. Early identification of individuals at higher risk of developing metabolic complications through adipose tissue dysfunction assessment and the staging of obesity and its transient phenotypes can contribute to improve therapeutic decision-making.

Impact of Beer and Nonalcoholic Beer Consumption on the Gut Microbiota: A Randomized, Double-Blind, Controlled Trial.

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.

Intermittent energy restriction ameliorates adipose tissue-associated inflammation in adults with obesity: A randomised controlled trial.

BACKGROUND & AIMS: Although intermittent energy restriction (IER) seems to be as effective as continuous energy restriction (CER) for weight loss, there is still a need to determine the putative effect of this strategy upon the metabolic-inflammatory status. This study aimed to compare the effects of IER versus CER on cardiometabolic and inflammatory markers, over a 12-week period, in adults with obesity. METHODS: Twenty-eight Norwegian adults (20-55 years) with obesity [body mass index: 35.4 (3.7) kg/m2] from a clinical trial (NCT02169778) who completed a 12-weeks diet-induced weight loss as IER (n = 14) or CER (n = 14) were included in this study. Cardiometabolic, adipokines and inflammatory markers were evaluated at baseline and after the intervention. Plasma levels of 13 inflammatory cytokines and chemokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-33) and 4 adipokines (adiponectin, adipsin, leptin and resistin) were measured through multiplex bead-based flow cytometric immunoassays. RESULTS: Both interventions resulted in comparable reductions in fasting glucose and insulin concentrations, lipid profile biomarkers, and adipokines. There were significant differences in HOMA-IR between interventions, with a more pronounced reduction in the IER group (-3.7 vs -1.6, P = 0.040). Inflammatory cytokines and chemokines decreased significantly in the IER group only. Differences in the relative changes of IL-1ß (-48.5 vs 58.2%, P = 0.011), IFN-γ (-53.2 vs 45.1%, P = 0.023), MCP-1 (-22.0 vs 17.4%, P = 0.023), IL-18 (-40.8 vs 10.1%, P = 0.019), IL-23 (-64.8 vs 44.0%, P = 0.011) and IL-33 (-53.4 vs 35.7%, P = 0.028) were statistically significant between groups, with improvements in the inflammatory profile in the IER group. CONCLUSIONS: Our results suggest that a 12-weeks intermittent energy restriction, in comparison to a continuous energy strategy, could be advantageous to reduce inflammation associated with obesity, and consequently improve insulin resistance, regardless of the amount of weight loss. Registered under ClinicalTrials.gov Identifier no. NCT02169778.

Intestinal Alkaline Phosphatase: A Review of This Enzyme Role in the Intestinal Barrier Function.

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.

Influence of Human Milk on Very Preterms' Gut Microbiota and Alkaline Phosphatase Activity.

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.

A Pilot Study on the Metabolic Impact of Mediterranean Diet in Type 2 Diabetes: Is Gut Microbiota the Key?

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.