Nutrição e genes em doenças intestinais

Tese de doutoramento, Ciências e Tecnologias da Saúde (Nutrição), Universidade de Lisboa, Faculdade de Medicina, 2011A nutrição é um dos principais factores modificáveis das doenças crónicas. Para além da sua indispensável função como veículo de nutrientes para o organismo, desempenha também um efeito fisiológico primordial ao ser parte integrante de muitas reacções ao nível celular. É sabido que por um lado os nutrientes podem alterar a expressão e transcrição genética condicionando mecanismos envolvidos na doença, e por outro podem também influenciar a predisposição para certas patologias como resultado da variabilidade genética individual. Este último aspecto poderá justificar respostas diferentes a estímulos nutricionais idênticos frequentemente detectadas em estudos que avaliam a relação entre dieta e doença. No cancro do cólon e recto (CCR) e na doença de Crohn (DC), duas patologias que afectam o tracto gastrintestinal influenciando a relação individuo/dieta e consequente metabolização dos nutrientes, muita atenção é dada ao estado nutricional dos indivíduos. São vários os estudos que avaliam não só a importância dos nutrientes/alimentos no risco de doença, como também no comportamento e actividade da mesma. Apesar dos inúmeros estudos, os seus resultados são muitas vezes discordantes em ambas as doenças; nalguns, determinados nutrientes parecem ser ou protectores ou promotores, ao passo que noutros esse efeito já não se observa. A hipótese em questão parece poder estar relacionada com a heterogeneidade genética das populações em estudo. O conjunto dos quatro estudos que compõem esta tese pretende explorar a influência de variáveis nutricionais e genéticas no desenvolvimento de duas doenças intestinais, em concreto o CCR e a DC. Os estudos pretendem dar a conhecer de forma mais pormenorizada o padrão e estado nutricional de duas populações distintas. Foram igualmente estudados alguns exemplos de nutrigenética: a) foi estimado o risco de CCR associado à interacção entre a ingestão de determinados nutrientes e polimorfismos de genes de susceptibilidade, e de metilação do ácido desoxirribonucleico (DNA); b) no caso da DC, uma doença inflamatória, avaliou-se o efeito da interacção entre os polimorfismos em genes que codificam as citocinas pró e anti-inflamatórias e o tipo de gordura da dieta, também esta com influência no perfil inflamatório

Diet, microbiota, and gut permeability : the unknown triad in rheumatoid arthritis

Copyright © 2018 Guerreiro, Calado, Sousa and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut dysbiosis can critically contribute to the development of rheumatic diseases, including rheumatoid arthritis (RA). Of interest, an adherence to a Mediterranean diet has been linked to a reduction in mortality and morbidity in patients with inflammatory diseases. Diet and intestinal microbiota are modifying factors that may influence intestinal barrier strength, functional integrity, and permeability regulation. Intestinal microbiota may play a crucial role in RA pathogenesis, but up to now no solid data has clarified a mechanistic relationship between gut microbiota and the development of RA. Nonetheless, microbiota composition in subjects with RA differs from that of controls and this altered microbiome can be partially restored after prescribing disease modifying antirheumatic drugs. High levels of Prevotella copri and similar species are correlated with low levels of microbiota previously associated with immune regulating properties. In addition, some nutrients can alter intestinal permeability and thereby influence the immune response without a known impact on the microbiota. However, critical questions remain to be elucidated, such as the way microbiome fluctuates in relation to diet, and how disease activity may be influenced by changes in diet, microbiota or diet-intestinal microbiota equilibrium.info:eu-repo/semantics/publishedVersio

Diet as a modulator of intestinal microbiota in rheumatoid arthritis

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Rheumatoid arthritis (RA) is a chronic immune-driven inflammatory disease characterised by synovial inflammation, leading to progressive cartilage and bone destruction, impacting patients’ functional capacity and quality of life. Patients with RA have significant differences in gut microbiota composition when compared to controls. Intestinal dysbiosis influences the intestinal barrier strength, integrity and function, and diet is considered the main environmental factor impacting gut microbiota. Over the last few years, researchers have focused on the influence of single components of the diet in the modulation of intestinal microbiota in RA rather than whole dietary patterns. In this review, we focus on how the Mediterranean diet (MD), a whole dietary pattern, could possibly act as an adjuvant therapeutic approach, modulating intestinal microbiota and intestinal barrier function in order to improve RA-related outcomes. We also review the potential effects of particular components of the MD, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fibre.info:eu-repo/semantics/publishedVersio

Body image perception in people with type 2 diabetes: does perceived image match reality?

Rationale: Body image misperception and body image dissatisfaction can lead to underestimation of weight and less predisposition to weight control

5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors

Thymidylate synthase, as a rate-limiting step in DNA synthesis, catalyses the conversion of dUMP into dTMP using 5,10-methylenotetrahydrofolate as the methyl donor. Two polymorphisms have been described in this gene: a repeat polymorphism in the 5' promoter enhancer region (3R versus 2R) and a 6 bp deletion in the 3' unstranslated region. Both of these may affect protein levels. The present case control study was aimed at investigating the influence of these two polymorphisms on the development of colorectal cancer (CRC), as well as their potential interaction with folate, vitamin B6 and vitamin B12 intake. A total of 196 cases and 200 controls, matched for age and sex distribution, were included in the study. No association was found between CRC and the 28 bp repeat polymorphism, but it was observed that individuals with the 6 bp/del and del/del genotypes had a significantly lower risk of developing the disease (OR=0.47; 95% CI 0.30-0.72). A combined genotype (2R/2R; 6 bp/del+del/del) was also found, which was associated with an even lower risk of developing of the disease (OR=0.42; 95% CI 0.26-0.69). No significant interaction between these polymorphisms and vitamin intake was observed. These results indicate for the first time that the 6 bp/del allele might be a protective factor in the development of CRC, independent of the intake of methyl group donors

Let’s review the gut microbiota in systemic lupus erythematosus

© The Author(s) 2022. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, andSystemic lupus erythematosus (SLE) is a chronic, immune-mediated disease associated with significant morbidity and mortality. New evidence suggests that diet, gut microbiota, intestinal permeability, and endotoxemia may modulate chronic inflammation and disease activity in SLE. This review focus on what is known about the gut microbiota in lupus mouse models and SLE patients and the possible mechanisms that connect the gut microbiota with SLE. It included 29 studies (12 animal studies, 15 human studies, and 2 included data on both), with variable results regarding alpha and beta-diversity and gut microbiota composition between lupus-mouse models and SLE patients. Ruminococcus ( R.) gnavus was significantly increased in lupus nephritis (LN) in one study, but this was not corroborated by others. Despite the different results, mechanistic lupus mouse model studies have shown that gut microbiota can modulate disease activity. Interestingly, pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by a vaccine targeting the pathobiont. Moreover, studies on fecal transplants and diet on different lupus mouse models showed an effect on disease activity. In SLE patients, a higher adherence to the Mediterranean diet was associated with lower disease activity, which may be explained by the connection between diet and gut microbiota. Although gut dysbiosis has been observed in SLE patients and lupus mouse models, it remains to clarify if it is a cause or a consequence of the disease or its treatments. Further studies with larger and well-characterized populations will undoubtedly contribute to deciphering the role of gut microbiota in SLE development, progression, and outcome.info:eu-repo/semantics/publishedVersio

Probiotic supplementation for Rheumatoid Arthritis: a promising adjuvant therapy in the gut microbiome era

Copyright © 2021 Ferro, Charneca, Dourado, Guerreiro and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.info:eu-repo/semantics/publishedVersio

Nutrientes funcionais e resposta inflamatória em indivíduos com doença inflamatória intestinal

As doenças Inflamatórias Intestinais (DII) caracterizam-se por um processo inflamatório crónico que afeta o trato gastrointestinal. Para além dos fatores ambientais, evidência recente sugere que determinados compostos alimentares (CA) podem modular a microbiota intestinal e influenciar de forma positiva, ou negativa, a resposta inflamatória, bem como o decurso destas doenças. Objetivo do estudo: Estudar o efeito da ingestão de CA nos marcadores inflamatórios em indivíduos com DII.info:eu-repo/semantics/publishedVersio

Functional food components, intestinal permeability and inflammatory markers in patients with inflammatory bowel disease

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Inflammatory bowel diseases (IBD) are characterized by a chronic inflammatory process that affects the intestinal barrier structure. Recent evidence suggests that some food components can influence the integrity of the intestinal barrier and thus its permeability. We aimed at assessing the effect of food components on the intestinal permeability (IP) and on inflammatory markers in individuals with IBD by a single-blind randomized clinical study. Of the 53 individuals included, 47% (n = 25) had been diagnosed with IBD. The participants were divided into 4 groups. IBD patients were allocated to intervention group (n = 14) vs. no intervention group (n = 11), and the same happened with 28 control participants without disease (n = 14 in intervention group vs. n = 14 without intervention). Symptomatology, nutritional status, biochemical parameters (specifically serum zonulin (ZO) to measure IP) were evaluated on all individuals on an eight week period following a diet plan with/without potentially beneficial foods for the IP. At the beginning of the study, there were no significant differences in ZO values between individuals with and without IBD (p > 0.05). The effect of specific food components was inconclusive; however, a trend in the reduction of inflammatory parameters and on the prevalence of gastrointestinal symptomatology was observed. More controlled intervention studies with diet plans, including food components potentially beneficial for the integrity of the intestinal barrier, are of the utmost importance.info:eu-repo/semantics/publishedVersio

A low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits

Introduction: Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. Methods: A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counseling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. Results: The studied cohort was 37% overweight, 34% obese (average body-mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body-mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgia symptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the "Diet adherence" (85%). "Satisfaction with improvement of symptoms" (76%), showed correlating with "diet adherence" (r = 0.65; p < 0.01). Conclusions: Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgia symptoms.info:eu-repo/semantics/publishedVersio