1. Introduction

Diabetes mellitus type two (DM2) is a complex pathology, it depends of the interaction of genetic, epigenetic, environmental, and lifestyle factors [1]. This disease has generated an epidemiological worldwide impact, with a current report of 425 million adults having the disease according to the International Diabetes Federation (IDF). Currently, the last report of the year 2017, the epidemiological data showed an increment of 10 million cases diagnosed respect to 2015 [2]. According to the IDF, projection for 2045 is 650 million subjects with DM2. North America and the Caribbean have the highest prevalence of this disease (11%), where an increase of 62% is expected for the same period [3].

2. Nutritional treatment and new perspectives

A prebiotic is defined as "a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon" [17]. Modification encouraged by prebiotics on the composition of HIM leads to the predominance of a few of the potentially health-promoting bacteria, especially, but not exclusively, Lactobacilli and Bifidobacteria [18]. Some prebiotics pass by the small intestine to the lower gut and become accessible for probiotic bacteria without being utilized by other intestinal bacteria [19]. Lactulose, galacto-oligosaccharides, fructo-oligosaccharides, inulin, and its hydrolysates, malto-oligosaccharides, and resistant starch are prebiotics normally used in the

New Insights into Alleviating Diabetes Mellitus: Role of Gut Microbiota and a Nutrigenomic Approach

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The definition used at present was given by the Food and Agriculture Organization of the United Nations World Health Organization, according to which probiotics are redefined as "live microorganisms which when are administered in adequate amounts confer a health benefit on the host." In relation to foods, the definition can be adjusted to beneficial effect exerted by microorganisms "when are consumed in adequate amounts as part of food" [17, 21].

Functional properties of β-glucans have been particularly attributed to the fact that these create viscous solutions in aqueous solution, as occurs in the digestive tract [22, 23]. This viscosity causes β-glucans to delay gastric emptying and interfere with the contact between pancreatic enzymes and their substrates in the intestinal lumen, slowing the digestion and absorption processes of nutrients [24]. This property could explain the effect of β-glucans on the reduction

Another pivotal property of fungi/yeasts β-glucans is the modulation of the immune system [27, 28]. This effect could be due to the ability of β-glucans to stimulate receptors of the innate immune system present in the membrane of enterocytes, M cells and dendritic cells, improving the phagocytic activity of macrophages and antimicrobial activity of mononuclear cells and neutrophils [29–31]. This type of β-glucans would also prevent the promotion and progression of certain types of cancer, acting synergistically with monoclonal antibodies and chemotherapy [32, 33]. This stimulation of immunity would be achieved by increasing the secretion of pro-inflammatory cytokines and chemokines [34]. The main receptor involved in the effect of B-glucans immunity is Dectin-1, even though there is also a role for the receptor 3 of the complement, TLR-2, TLR-6 and the "scavengers" receptors [35, 36]. Dectin-1, known in human beings as β-glucans receptor (βGR), is a member of the pattern recognition receptors (PRR)

of plasma cholesterol concentrations and the glycemic index [25, 26].

2.1. Prebiotics derived from functional fiber sources

human diet [20, 21].

2.1.1. Betaglucans

2.1.1.1. Cereal β-glucans

2.1.1.2. Yeasts and fungi β-glucans

In the multidisciplinary treatment of this pathology, dietotherapy has been specifically considered as a critical control point in the international guidelines for DM2 [4, 5]. Recently, important advances in nutrition management have been developed associated to nutritional genomics, whose objective focuses on the interaction between the bioactive components of food and the human genome, this approach includes studies of nutrigenetics, nutrigenomics, and epigenetic modifications caused by nutrients [6].

Some investigations have used nutrigenomics to illustrate the modulation mechanism of specific fatty acids on gene expression, producing an impact on human metabolism [7, 8]. A common approach is the examination of individual levels of mRNA in relation to nutrient intake [9]. Tests with carbohydrates and dietary components such as fiber show a relationship between specific polymorphisms and the effect on insulin resistance [10]. In this sense, in a recent review, the effectiveness of the supply of fermentable carbohydrates on human metabolism is explained [11].

Furthermore, new advances in study of the composition of the human microbiota have shown an evident relationship between Human Intestinal Microbiota (HIM) and DM2 [12]. In this context, a significantly greater association of Firmicutes/Bacteroidetes in DM2 has been observed when is compared with normal weight and obese subjects [13].

New focus of nutritional treatment and its potential epigenetic effect constitute a panacea in the modification of the diabetic patient's microbiota [14]. The HIM is affected by the ingestion of bioactive compounds, showing prebiotic or probiotic effects, whose action can help to generate the growth of beneficial bacteria, such as Bifidobacterium and Bacteroidetes. The development of personalized nutritional methods considering the genomic information, use of prebiotics from novel sources of functional fibers (Fructo-oligosaccharides FOS, betaglucans) [15], consumption of carbohydrates with low-glycemic index (GI), as well as the use of monosaccharide sweeteners with potential prebiotic activity, such as (tagatose) [16], would allow to generate a new therapeutic orientation for the control and prevention of this pathology. These dietary practices are important as part of the near future and will be analyzed in this chapter. Finally, a description in nutrigenomics advances and the effect of prebiotics consumption on modification of HIM are shown and its relationship with DM2 will be discussed.
