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Polyphenols duplibiotic role in intestinal inflammatory disease: focus on next-generation akkermansia muciniphila
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As doenças inflamatórias intestinais (DII), que incluem a doença de Crohn (DC) e a colite ulcerosa (CU), representam uma condição inflamatória crónica do trato digestivo. A patogénese da DII é complexa e multifatorial, resultando da interação de fatores ambientais, predisposição genética, disbiose intestinal e desregulação do sistema imunológico; contudo, a etiologia exata da doença permanece desconhecida. A redução da abundância de Akkermansia muciniphila foi observada em doentes com DII, sugerindo um possível papel na progressão da doença e um potencial alvo para estratégias terapêuticas. A. muciniphila é uma bactéria degradadora de mucina, que exibe efeitos protetores na integridade da barreira intestinal e propriedades anti-inflamatórias, sendo reconhecida como um probiótico de última geração pelo seu potencial benefício na saúde intestinal. No entanto, o seu papel exato e os mecanismos subjacentes na DII requerem mais investigação.
Os polifenóis (PPs) são compostos bioativos encontrados em alimentos de origem vegetal, com propriedades prebióticas, anti-inflamatórias, antioxidantes e antimicrobianas. Evidências emergentes sugerem um efeito "duplibiótico" onde os PPs aumentam a abundância de A. muciniphila e simultaneamente beneficiam a saúde intestinal, principalmente devido aos seus efeitos antimicrobianos. Esta tese investiga a interação entre PPs e A. muciniphila, explorando os seus potenciais efeitos benéficos na modulação da microbiota intestinal, na integridade da mucosa e na redução da inflamação na DII.
Esta revisão seguiu as diretrizes PRISMA-ScR. A pesquisa bibliográfica, realizada entre 2012 e 2023 (outubro) na PubMed, focou-se em estudos quase experimentais e experimentais usando modelos in vitro, modelos animais e humanos. A estratégia de pesquisa incluiu palavras-chave como "Polifenóis", "Doença Inflamatória Intestinal", "Microbiota Intestinal" e "Akkermansia muciniphila", e os estudos foram analisados utilizando o software Covidence. Apenas foram incluídos artigos originais que reportavam efeitos dos PPs na abundância de A. muciniphila na DII. As principais descobertas relacionadas com classe de polifenóis, modulação da microbiota intestinal e resultados clínicos foram sintetizadas em tabelas para avaliar o seu potencial papel terapêutico na DII.
Num total de 47 artigos incluídos nesta revisão, analisou-se o impacto de classes específicas de PPs (flavonoides, ácidos fenólicos e outros) na abundância de A. muciniphila, na diversidade e composição da microbiota intestinal (nomeadamente em bactérias aeróbicas e anaeróbicas), e em outros parâmetros relacionados com a DII.
As evidências destacam a capacidade de classes distintas de PPs, particularmente flavonoides, de restaurar a função da barreira intestinal, reduzir a inflamação e promover a regulação imunológica, particularmente em modelos animais, bem como a capacidade de estimular a abundância de A. muciniphila e aumentar os seus efeitos benéficos. As descobertas sugerem que dietas ricas em PPs podem servir como uma terapia coadjuvante promissora para a DII, promovendo uma mudança em direção à eubiose e melhorando a função da barreira intestinal. A existência de um efeito duplibiótico dos PPs na DII devido à modulação específica de A. muciniphila merece investigação adicional, de forma a elucidar os mecanismos moleculares subjacentes, com vista a desenvolver estratégias terapêuticas direcionadas capazes de melhorar a qualidade de vida de doentes com DII.
Inflammatory bowel diseases (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), represents a chronic inflammatory condition of the digestive tract. The pathogenesis of IBD is complex and multifactorial, resulting from an intricate interplay of environmental factors, genetic predisposition, gut dysbiosis, and immune system dysregulation; however, the exact etiology of the disease remains unknown. Reduction of Akkermansia muciniphila abundance has been observed in IBD patients, suggesting a possible role in disease progression and a potential target for therapeutic strategies. A. muciniphila, a mucin-degrading bacteria, exhibits protective effects on gut barrier integrity and has anti-inflammatory properties, being recognized as a next-generation probiotic for its potential to benefit gut health. However, the precise role and underlying mechanisms in IBD require further investigation. Polyphenols (PPs), bioactive compounds found in plant-based foods, exhibit prebiotic, anti-inflammatory, antioxidant, and antimicrobial properties. Emerging evidence suggests a novel "duplibiotic" effect where PPs enhance the abundance of A. muciniphila while simultaneously benefiting gut health, namely by having antimicrobial effects. This thesis investigates the interplay between PPs and A. muciniphila, exploring their potential beneficial effects in modulating gut microbiota, improving intestinal mucosal integrity, and reducing inflammation in IBD. This scoping review was conducted following the PRISMA-ScR guidelines. The literature search, performed from 2012 to 2023 (October) in PubMed, focused on quasi-experimental and experimental studies using in vitro models, animal models, and human participants. The search strategy incorporated keywords like "Polyphenols," "Inflammatory Bowel Disease," "Gut Microbiota," and "Akkermansia muciniphila," and studies were screened using Covidence software. Only original research exploring the effects of polyphenols on A. muciniphila abundance in IBD was included. Key findings related to polyphenol class, gut microbiota modulation, and clinical outcomes were synthesized and presented in tables to evaluate their potential therapeutic role in IBD management. Through a comprehensive analysis of a final number of 47 articles included in this scoping review, the impact of specific PPs classes (flavonoids, phenolic acids, and others) on A. muciniphila abundance, gut microbiota diversity and composition (namely on aerobic and anaerobic bacteria), as well as on IBD-related outcomes. Evidence from the literature highlights the capacity of distinct PPs classes, particularly flavonoids, to restore intestinal barrier function, reduce inflammation, and promote immune regulation, particularly in animal models, as well as the ability to stimulate A. muciniphila abundance and enhance its beneficial effects. The findings suggest that PP-rich diets could serve as a promising co-adjuvant therapy for IBD, promoting a shift towards eubiosis and improving gut barrier function. The existence of a duplibiotic effect of PPs on IBD due to specific modulation of A. muciniphila deserve further clarification. In particular, further research is required to elucidate the precise molecular mechanisms underlying this interaction between PPs and A. muciniphila, in order to develop targeted therapeutic strategies able to improve IBD patients’ quality of life.
Inflammatory bowel diseases (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), represents a chronic inflammatory condition of the digestive tract. The pathogenesis of IBD is complex and multifactorial, resulting from an intricate interplay of environmental factors, genetic predisposition, gut dysbiosis, and immune system dysregulation; however, the exact etiology of the disease remains unknown. Reduction of Akkermansia muciniphila abundance has been observed in IBD patients, suggesting a possible role in disease progression and a potential target for therapeutic strategies. A. muciniphila, a mucin-degrading bacteria, exhibits protective effects on gut barrier integrity and has anti-inflammatory properties, being recognized as a next-generation probiotic for its potential to benefit gut health. However, the precise role and underlying mechanisms in IBD require further investigation. Polyphenols (PPs), bioactive compounds found in plant-based foods, exhibit prebiotic, anti-inflammatory, antioxidant, and antimicrobial properties. Emerging evidence suggests a novel "duplibiotic" effect where PPs enhance the abundance of A. muciniphila while simultaneously benefiting gut health, namely by having antimicrobial effects. This thesis investigates the interplay between PPs and A. muciniphila, exploring their potential beneficial effects in modulating gut microbiota, improving intestinal mucosal integrity, and reducing inflammation in IBD. This scoping review was conducted following the PRISMA-ScR guidelines. The literature search, performed from 2012 to 2023 (October) in PubMed, focused on quasi-experimental and experimental studies using in vitro models, animal models, and human participants. The search strategy incorporated keywords like "Polyphenols," "Inflammatory Bowel Disease," "Gut Microbiota," and "Akkermansia muciniphila," and studies were screened using Covidence software. Only original research exploring the effects of polyphenols on A. muciniphila abundance in IBD was included. Key findings related to polyphenol class, gut microbiota modulation, and clinical outcomes were synthesized and presented in tables to evaluate their potential therapeutic role in IBD management. Through a comprehensive analysis of a final number of 47 articles included in this scoping review, the impact of specific PPs classes (flavonoids, phenolic acids, and others) on A. muciniphila abundance, gut microbiota diversity and composition (namely on aerobic and anaerobic bacteria), as well as on IBD-related outcomes. Evidence from the literature highlights the capacity of distinct PPs classes, particularly flavonoids, to restore intestinal barrier function, reduce inflammation, and promote immune regulation, particularly in animal models, as well as the ability to stimulate A. muciniphila abundance and enhance its beneficial effects. The findings suggest that PP-rich diets could serve as a promising co-adjuvant therapy for IBD, promoting a shift towards eubiosis and improving gut barrier function. The existence of a duplibiotic effect of PPs on IBD due to specific modulation of A. muciniphila deserve further clarification. In particular, further research is required to elucidate the precise molecular mechanisms underlying this interaction between PPs and A. muciniphila, in order to develop targeted therapeutic strategies able to improve IBD patients’ quality of life.
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Keywords
Doença inflamatória intestinal Akkermansia muciniphila Polifenóis Microbiota intestinal Saúde intestinal Inflammatory bowel disease Polyphenols Gut Microbiota Gut health