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Intermittent energy restriction ameliorates adipose tissue-associated inflammation in adults with obesity: A randomised controlled trial.
Castela, I, Rodrigues, C, Ismael, S, Barreiros-Mota, I, Morais, J, Araújo, JR, Marques, C, Silvestre, MP, Ângelo-Dias, M, Martins, C, et al
Clinical nutrition (Edinburgh, Scotland). 2022;(8):1660-1666
Abstract
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-1β, 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-1β (-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.
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Tailoring gut microbiota with a combination of Vitamin K and probiotics as a possible adjuvant in the treatment of rheumatic arthritis: a systematic review.
Pereira, L, Monteiro, R
Clinical nutrition ESPEN. 2022;:37-49
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.
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Gut Microbiota, in the Halfway between Nutrition and Lung Function.
Espírito Santo, C, Caseiro, C, Martins, MJ, Monteiro, R, Brandão, I
Nutrients. 2021;(5)
Abstract
The gut microbiota is often mentioned as a "forgotten organ" or "metabolic organ", given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a "good" microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut-lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.
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The Secretome landscape of Escherichia coli O157:H7: Deciphering the cell-surface, outer membrane vesicle and extracellular subproteomes.
Monteiro, R, Chafsey, I, Ageorges, V, Leroy, S, Chambon, C, Hébraud, M, Livrelli, V, Pizza, M, Pezzicoli, A, Desvaux, M
Journal of proteomics. 2021;:104025
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Abstract
Among diarrheagenic E. coli (DEC), enterohaemorrhagic E. coli (EHEC) are the most virulent anthropozoonotic agents. The ability of bacterial cells to functionally interact with their surrounding essentially relies on the secretion of different protein effectors. To experimentally determine the repertoire of extracytoproteins in E. coli O157:H7, a subproteomic analysis was performed not only considering the extracellular milieu but the cell surface and outer membrane vesicles. Following a secretome-based approach, the proteins trafficking from the interior to the exterior of the cell were depicted considering cognate protein transport systems and subcellular localisation. Label-free quantitative analysis of the proteosurfaceome, proteovesiculome and exoproteome from E. coli O157:H7 grown in three different nutrient media revealed differential protein expression profiles and allowed defining the core and variant subproteomes. Network analysis further revealed the higher abundance of some protein clusters in chemically defined medium over rich complex medium, especially related to some outer membrane proteins, ABC transport and Type III secretion systems. This first comprehensive study of the EHEC secretome unravels the profound influence of environmental conditions on the extracytoplasmic proteome, provides new insight in the physiology of E. coli O157:H7 and identifies potentially important molecular targets for the development of preventive strategies against EHEC/STEC. SIGNIFICANCE Escherichia coli O157:H7 is responsible for severe diarrhoea especially in young children. Despite years of investigations, the global view of the extracytoplasmic proteins expressed in this microorganism was eluded. To provide the first comprehensive view of the secretome landscape of E. coli O157:H7, the exoproteome, proteosurfaceome and proteovesiculome were profiled using growth conditions most likely to induce changes in bacterial protein secretion. The profound influence of growth conditions on the extracytoplasmic proteome was unravelled and allowed identifying the core and variant subproteomes. Besides new insight in the physiology of enterohaemorrhagic E. coli, these proteins potentially constitute important molecular targets for the development of preventive strategies.
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Metabolically Healthy Obesity-Heterogeneity in Definitions and Unconventional Factors.
Brandão, I, Martins, MJ, Monteiro, R
Metabolites. 2020;(2)
Abstract
The concept of heterogeneity among obese individuals in their risk for developing metabolic dysfunction and associated complications has been recognized for decades. At the origin of the heterogeneity idea is the acknowledgement that individuals with central obesity are more prone to developing type 2 diabetes and cardiovascular disease than those with peripheral obesity. There have been attempts to categorize subjects according to their metabolic health and degree of obesity giving rise to different obese and non-obese phenotypes that include metabolically unhealthy normal-weight (MUHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Individuals belonging to the MHO phenotype are obese according to their body mass index although exhibiting fewer or none metabolic anomalies such as type 2 diabetes, dyslipidemia, hypertension, and/or unfavorable inflammatory and fribinolytic profiles. However, some authors claim that MHO is only transient in nature. Additionally, the phenotype categorization is controversial as it lacks standardized definitions possibly blurring the distinction between obesity phenotypes and confounding the associations with health outcomes. To add to the discussion, the factors underlying the origin or protection from metabolic deterioration and cardiometabolic risk for these subclasses are being intensely investigated and several hypotheses have been put forward. In the present review, we compare the different definitions of obesity phenotypes and present several possible factors underlying them (adipose tissue distribution and cellularity, contaminant accumulation on the adipose tissue, dysbiosis and metabolic endotoxemia imposing on to the endocannabinoid tone and inflammasome, and nutrient intake and dietary patterns) having inflammatory activation at the center.
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Family meal frequency and its association with food consumption and nutritional status in adolescents: A systematic review.
do Amaral E Melo, GR, Silva, PO, Nakabayashi, J, Bandeira, MV, Toral, N, Monteiro, R
PloS one. 2020;(9):e0239274
Abstract
This systematic review evaluated the association between frequency of family meals (FFM) and nutritional status (NS) and/or food consumption (FC) in adolescents. The protocol was registered with PROSPERO (CRD42017062180) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. No publication date, language, or meal type restrictions were imposed. Only full-text original articles were included; qualitative studies were excluded. Studies were identified by searching 5 electronic databases (PubMed, Web of Science, Scopus, BVS Brazil, and Adolec) and gray literature (Google Scholar) and by scanning reference lists of included articles. Risk of bias was assessed using the Newcastle-Ottawa scale for cohort and cross-sectional studies. Initial search yielded 2001 results and 47 articles were included. An updated literature search added 3 articles. Of the 50 studies included, 25 studied the association between FFM and NS, 32 investigated the association between FFM and FC, being that seven studies analyzed both outcomes. Thirty-four were cross-sectional studies, 12 were longitudinal studies, and 4 studies analyzed both cross-sectional and longitudinal data. Thirty-five studies were rated as having good quality, whereas 19 were of fair quality. Sample size ranged from 140 to 102 072 participants. Most investigations evaluated the frequency of breakfast, lunch, and/or dinner/supper/evening meals over a 1-week period. Seventeen studies identified a positive relationship between high FFM and better NS, and 26 found a positive association between high FFM and better FC. In conclusion, this review showed an association between FFM and healthy dietary patterns, such as increased consumption of fruits and vegetables. Further research is needed to understand the association between FFM and NS, since some studies showed a protective role of family meals against obesity in this age group, whereas other studies identified no significant association between these variables.
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Background pharmacological therapy in the ANTHEM-HF: comparison to contemporary trials of novel heart failure therapies.
Premchand, RK, Sharma, K, Mittal, S, Monteiro, R, Libbus, I, Ardell, JL, Gregory, DD, KenKnight, BH, Amurthur, B, DiCarlo, LA, et al
ESC heart failure. 2019;(5):1052-1056
Abstract
AIMS: Clinical trials of new heart failure (HF) therapies administer guideline-directed medical therapy (GDMT) as background pharmacologic treatment (BPT). In the ANTHEM-HF Pilot Study, addition of autonomic regulation therapy to GDMT significantly improved left ventricular function, New York Heart Association (NYHA) class, 6 min walk distance, and quality of life in patients with HF with reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare BPT in ANTHEM-HF with two other trials of novel HF therapies: the PARADIGM-HF study of sacubitril-valsartan and the SHIFT study of ivadrabine. All three studies evaluated patients with HFrEF, and the recommendations for use of GDMT were similar. A left ventricular ejection fraction ≤40% was required for entry into ANTHEM-HF and PARADIGM-HF and ≤35% for SHIFT. NYHA 2 or 3 symptoms were required for entry into ANTHEM-HF, and patients with predominantly NYHA 2 or 3 symptoms were enrolled in PARADIGM-HF and SHIFT. METHODS AND RESULTS Data on BPT were obtained from peer-reviewed publications and the public domain. Pearson's χ2 test was used to evaluate differences in proportions, and Student's unpaired t-test was used to evaluate differences in mean values. The minimum period of stable GDMT required before randomization was longer in ANTHEM-HF: 3 months vs. 1 month in PARADIGM-HF and SHIFT, respectively. When compared with PARADIGM-HF and SHIFT, more patients in ANTHEM-HF received beta-blockers (100% vs. 93% and 89%, P < 0.04 and P < 0.007) and mineralocorticoid receptor antagonists (75% vs. 55% and 61%, P < 0.002 and P < 0.03). More patients in PARADIGM-HF received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker than in ANTHEM-HF or SHIFT (100% vs. 85%, P < 0.0001, and 100% vs. 91%, P < 0.001), which was related to PARADIGM's design. When beta-blocker doses in ANTHEM-HF and SHIFT were compared, significantly fewer patients in ANTHEM-HF received doses ≥100% of target (10% vs. 23%, P < 0.02), and fewer patients tended to receive doses ≥50% of target (17% vs. 26%, P = 0.11). When ANTHEM-HF and PARADIGM-HF were compared, more patients in ANTHEM-HF tended to receive doses ≥100% of target (10% vs. 7%, P = 0.36), and fewer patients tended to receive doses ≥50% of target (17% vs. 20%, P = 0.56). CONCLUSIONS Background treatment with GDMT in ANTHEM-HF compared favourably with that in two other contemporary trials of new HF therapies. The minimum period of stable GDMT required before randomization was longer, and GDMT remained unchanged for the study's duration. These findings serve to further support the potential role of autonomic regulation therapy as an adjunct to GDMT for patients with HFrEF.
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Metabolic Syndrome Features: Is There a Modulation Role by Mineral Water Consumption? A Review.
Costa-Vieira, D, Monteiro, R, Martins, MJ
Nutrients. 2019;11(5)
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Plain language summary
Metabolic syndrome, defined as having high blood pressure, triglycerides, blood glucose and being obese, is becoming an increasing worldwide health problem. It’s considered to be a result of modern-day life styles and there is no effective cure other than diet and life style interventions. This review paper looks at the mineral content and the alkalising effects of mineral water when consumed by participants with metabolic syndrome. The minerals within mineral water are thought to be more readily absorbed in the body than when consumed in foods and since Westernised diets are low in mineral content and high in acidity, consuming mineral water could help counteract mineral deficiencies and help to balance pH in those with metabolic syndrome. 20 studies, both animal and human, were selected for evaluation of the effect of mineral water on blood pressure, lipid profile, blood glucose and waist circumference. The authors conclude that mineral water is indeed beneficial to those with metabolic syndrome and can help counteract mineral deficiencies and balance pH. However, it is unclear whether mineral water in high quantities would be detrimental to a person with adequate mineral status and a pH within optimal range. Further studies are needed.
Abstract
Metabolic syndrome (MetSyn) promotes, among others, the development of atherosclerotic cardiovascular disease and diabetes. Its prevalence increases with age, highlighting the relevance of promoting precocious MetSyn primary prevention and treatment with easy-to-implement lifestyle interventions. MetSyn features modulation through mineral water consumption was reviewed on Pubmed, Scopus and Google Scholar databases, using the following keywords: metabolic syndrome, hypertension, blood pressure (BP), cholesterol, triglycerides, apolipoprotein, chylomicron, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein (HDL), glucose, insulin, body weight, body mass index, waist circumference (WC), obesity and mineral(-rich) water. Twenty studies were selected: 12 evaluated BP, 13 assessed total-triglycerides and/or HDL-cholesterol, 10 analysed glucose and/or 3 measured WC. Mineral waters were tested in diverse protocols regarding type and composition of water, amount consumed, diet and type and duration of the study. Human and animal studies were performed in populations with different sizes and characteristics. Distinct sets of five studies showed beneficial effects upon BP, total-triglycerides, HDL-cholesterol and glucose. WC modulation was not reported. Minerals/elements and active ions/molecules present in mineral waters (and their pH) are crucial to counterbalance their inadequate intake and body status as well as metabolic dysfunction and increased diet-induced acid-load observed in MetSyn. Study characteristics and molecular/physiologic mechanisms that could explain the different effects observed are discussed. Further studies are warranted for determining the mechanisms involved in the putative protective action of mineral water consumption against MetSyn features.
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A secretome view of colonisation factors in Shiga toxin-encoding Escherichia coli (STEC): from enterohaemorrhagic E. coli (EHEC) to related enteropathotypes.
Monteiro, R, Ageorges, V, Rojas-Lopez, M, Schmidt, H, Weiss, A, Bertin, Y, Forano, E, Jubelin, G, Henderson, IR, Livrelli, V, et al
FEMS microbiology letters. 2016;(16)
Abstract
Shiga toxin-encoding Escherichia coli (STEC) regroup strains that carry genes encoding Shiga toxin (Stx). Among intestinal pathogenic E. coli, enterohaemorrhagic E. coli (EHEC) constitute the major subgroup of virulent STEC. EHEC cause serious human disease such as haemorrhagic colitis and haemolytic-uremic syndrome. While EHEC have evolved from enteropathogenic E. coli, hybrids with enteroaggregative E. coli have recently emerged. Of note, some enteroinvasive E. coli also belong to the STEC group. While the LEE (locus of enterocyte effacement) is a key and prominent molecular determinant in the pathogenicity, neither all EHEC nor STEC contain the LEE, suggesting that they possess additional virulence and colonisation factors. Currently, nine protein secretion systems have been described in diderm-lipopolysaccharide bacteria (archetypal Gram-negative) and can be involved in the secretion of extracellular effectors, cell-surface proteins or assembly of cell-surface organelles, such as flagella or pili. In this review, we focus on the secretome of STEC and related enteropathotypes, which are relevant to the colonisation of biotic and abiotic surfaces. Considering the wealth of potential protein trafficking mechanisms, the different combinations of colonisation factors and modulation of their expression is further emphasised with regard to the ecophysiology of STEC.