Gut microorganisms as promising targets for the management of type 2 diabetes

Abstract

Each human intestine harbours not only hundreds of trillions of bacteria but also bacteriophage particles, viruses, fungi and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. An increasing number of data obtained during the last 10 years have indicated changes in gut bacterial composition or function in type 2 diabetic patients. Analysis of this 'dysbiosis' enables the detection of alterations in specific bacteria, clusters of bacteria or bacterial functions associated with the occurrence or evolution of type 2 diabetes; these bacteria are predominantly involved in the control of inflammation and energy homeostasis. Our review focuses on two key questions: does gut dysbiosis truly play a role in the occurrence of type 2 diabetes, and will recent discoveries linking the gut microbiota to host health be helpful for the development of novel therapeutic approaches for type 2 diabetes? Here we review how pharmacological, surgical and nutritional interventions for type 2 diabetic patients may impact the gut microbiota. Experimental studies in animals are identifying which bacterial metabolites and components act on host immune homeostasis and glucose metabolism, primarily by targeting intestinal cells involved in endocrine and gut barrier functions. We discuss novel approaches (e.g. probiotics, prebiotics and faecal transfer) and the need for research and adequate intervention studies to evaluate the feasibility and relevance of these new therapies for the management of type 2 diabetes.

Participation of the microbiome in the pathogenesis of diabetes mellitus

“…The agenda of these studies covers multiple directions of the pathogenesis of such metabolic disorders as changes in the immunological reactions contributing to the incidence of diabetes, as well as pathogenetic significance of inflammations in these diseases [12,[21][22][23][24][25].…”

“…It is important to establish the pathogenic relation between the gut microbiota and diabetes since it might lead to the development of integrated strategies using probiotics to prevent and treat these metabolic disorders [21]. During the last decade, evidence has accumulated to support a role for gut microbiota in glycaemic control and type 2 diabetes.…”

Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

“…The abundance and composition of gut microbiota are highly variable in the context of different conditions contributing to development of various diseases [3,4]. In recent years, a huge number of studies have revealed the critical roles of gut microbiota in affecting development of metabolic diseases including type 1 and 2 diabetes [5,6], obesity [7][8][9][10], cardiovascular disease [11][12][13], and chronic liver diseases [14].…”

Efeito dos compostos fenólicos do camu-camu e do cupuaçu no desenvolvimento da obesidade e diabetes mellitus tipo 2

“…Estudos tem demonstrado que dietas ricas em gorduras e açúcares são capazes de modular a microbiota, aumentando a quantidade de microorganismos patogênicos, alteração conhecida como disbiose (MYLES, 2014;TREMAROLI;BACKHED, 2012). Com isso ocorre o aumento da produção de lipopolissacarídeos (LPS) derivados de bactérias gran negativas, que apresentam efeitos semelhantes aos das gorduras, interagindo com os TLRs e acionando as vias inflamatórias e a endotoxemia (DELZENNE et al, 2015;TORRES-FUENTES et al, 2014;MYLES, 2014).…”

“…Estudos tem demonstrado que dietas ricas em gorduras e açúcares são capazes de modular a microbiota, aumentando a quantidade de microorganismos patogênicos, alteração conhecida como disbiose (MYLES, 2014;TREMAROLI;BACKHED, 2012). Com isso ocorre o aumento da produção de lipopolissacarídeos (LPS) derivados de bactérias gran negativas, que apresentam efeitos semelhantes aos das gorduras, interagindo com os TLRs e acionando as vias inflamatórias e a endotoxemia (DELZENNE et al, 2015;TORRES-FUENTES et al, 2014;MYLES, 2014).Adicionalmente, as dietas ricas em gorduras e a própria endotoxemia local podem reduzir a expressão de proteínas epiteliais das tigh junctions, aumentando assim a permeabilidade intestinal, o que facilitaria a entrada de lipopolissacarídeos na circulação sistêmica, bem como a entrada de lipídios (BOHN, 2014;. Assim, a microbiota intestinal pode influenciar a absorção de nutrientes tanto pelo aumento da permeabilidade intestinal quanto pelo desencadeamento de um mecanismo que leva à secreção do peptídio YY que está envolvido na inibição da motilidade intestinal, retardando o trânsito intestinal (FALLUCA et al, 2014) .…”