**1. Introduction**

Diabetes *mellitus* type 2 (DM2) is a global pandemic; although genetic factors can predispose subjects to suffer from it, external factors such as socioeconomic changes and cultural and eating habit changes have more contributions to increasing world prevalence [1], where overweight and obesity are considered as the main mediators of the disease. The number of cases of DM2 according to the International Diabetes Federation is 415 million adults by 2015. The risk death of subjects with DM is significantly higher than those without the disease, doubling it when we refer to cardiovascular death reason [2]. It has been determined that the gut microbiota (GM) is altered in subjects with type 2 diabetes, so studying its role in the development of pathology is essential to determine new approaches to treatment; it permits the identification of those bacteria beneficial to humans, from the bacterial genome recognition. The so-called microbiome correspond to the entire GM genome; it exceeds the size of the human genome, having about 500 times more genes that complement our coding; this bacterial ecosystem has evolved in a symbiotic relationship with human [3]; GM exerts nutritional, metabolic, and immunological functions that affect the human being. During the last decade, several studies have been reported on the effect of the GM on glycemic control [4]. In this context, GM in the epigenetic mechanisms of diabetes mellitus and the reprogramming of the cells is a novel and emerging concept. It is known that products derived from diet along with intestinal bacteria can change the epigenome of the host with favorable metabolic effects [5]. These microorganisms are essential for the biosynthesis of vitamins and hormones, as well as for the degradation of nondigestible dietary fibers and mucin in simple sugars and short-chain fatty acids [6]. Changes in the composition and function of the predominant GM are associated with an increased risk of DM2 and are linked to an increase in the number of *Bacteroides* [7] and *Clostridium* [8]. Specifically, the increase of *Firmicutes/ Bacteroidetes* ratio in the distal bowel, as well as the number of opportunistic pathogens, and in the production of endotoxins of Gram-negative bacteria is capable of modifying intestinal permeability. The metabolic syndrome is associated with changes in the framework of the GM that lead to low-grade inflammations, since the increased permeability of the intestinal membrane damaged by bacteria induces inflammation, through the epigenetic alteration of inflammatory molecules such as Toll-like receptors [9]. Mucus and glycocalyx layer mainly produced by *Bacteroides thetaiotaomicron*, *Akkermansia muciniphila*, and *Escherichia coli* cause chronic low-level inflammation, insulin resistance, and, lastly, DM2 [10]. Evidence demonstrates the link between diabetes and histone deacetylase (HDA), because the microorganisms producing butyrate, an HDA inhibitory molecule that promotes differentiation and cellular proliferation and insulin resistance [11], are decreased in diabetics [5]. On the other hand, it has been recognized that the microbiome has a direct effect on the immune and neuroendocrine system, constituting a new brain gut axis [12], in which the circadian rhythm plays a fundamental role [13]. The production of colonic serotonin [14, 15] by the microbiome, through the effect of short-chain fatty acids on enterochromaffin cells [13, 16, 17], would allow to relate this neurotransmitter to the metabolic processes as one of the possible etiopathogenic factors of DM2. The next challenges are focused on integrating the transcriptomic, epigenetic, proteomic, and metabolic information of the human genome and the microbiome into the nutritional treatment [2].

**2. Microbiome, epigenetics, and diabetes interactions (metabolic** 

Acetate participates in the cholesterol metabolism and lipogenesis in the host [25].

A cross-feeding effect has recently been described, for instance, *Bifidobacterium longum* growing in fructooligosaccharides (FOS) produces a conversion into lactate and promotes the growth of *Eubacterium hallii* that could not grow in the presence of FOS alone and converts it to butyrate [26]. Another example of cross feeding occurs when *Roseburia intestinalis* increases its growth in co-cultures with—the acetate contributor—*B. longum* [27, 28]. Two main routes of butyrate

**2.1. Microbiota metabolism**

The human intestinal microbiota (HIM) is composed of a complex community of microorganisms; more than 1000 species have been identified, where only a few are cultivable [18]. The gut microbiome corresponds to a total set of genes present in the HIM (about 3 million genes), approximately 150-fold human genome [19]. This microorganism participates as a counterpart of gut enzymatic activities by a diverse metabolic repertoire becoming an important contributor to the metabolism of the host [20]. Exploratory studies have been shown that play an important role in the etiology and development of many diseases, being considered as markers of the course of the disease. Some chronic illnesses in which HIM has been regarded are the inflammatory bowel disease (IBD), the irritable bowel syndrome (IBS), diarrhea, obesity, diabetes, and inclusive cancer. The recent role attributed to the microbiome and health has promoted the research to study the microorganism characteristics and the design of strategies to restore damage microbiome to a normal "state" by using a microbe inoculation strategy or by using dietary modification to feed specific species and help their development or otherwise consume foods or other substances that induce the extinguishment of some species in the intestine. The abundance and diversity of the intestinal bacteria are located mainly in the large intestine where it exerts its principal metabolic role. Bacteria are capable of hydrolyzing carbohydrates, lipids, and proteins principally; *saccharolytic* bacterial fermentation produces generally beneficial metabolites such as short-chain fatty acids (SCFAs) and gases. The three most abundant SCFAs detected in feces are acetate, propionate, and butyrate, in molar ratios of 3:1:1 to 10:2:1 [21]. Butyrate is recognized as the most important SCFA for human health and is absorbed by the epithelial cell of the colon in the proximal colon via passive diffusion and by active transport mechanisms. Some properties have been attributed to butyrate, for instance, being able to be used by colonocytes as energy source, the potential anticancer activity inducing apoptosis of colon cancer cells, its ability to regulate gene expression in host by inhibiting histone deacetylases [22], and the beneficial effects in glucose regulation by activation of gluconeogenesis in the gut via cAMP-dependent manner [23].On the other hand, propionate exerts a dual action in intestine and liver regulation of gluconeogenesis and is considered an important molecule for satiety signaling because of an interaction with G protein-coupled receptors GPR 41, GPR 43 receptors, and fatty acid receptors FFAR2 and FFAR3. The net effect of the conversion of propionate to glucose is the decrease of gluconeogenesis in the liver; this generates a reduction in the production of adiposity [23]. Acetate is the most abundant SCFA and is considered as essential metabolite for bacteria growth. *Faecalibacterium prausnitzii* will not grow in pure culture in the absence of acetate [24].

The Microbiome and the Epigenetics of Diabetes Mellitus

http://dx.doi.org/10.5772/intechopen.76201

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**pathways)**
