**4. Nutrigenomics and the microbiome**

In most chronic pathologies, environmental and genetic factors are involved because of a polygenic behavior. Recent research investigate the mechanisms involved in the dysfunction of a healthy phenotype to another with chronic dysfunction, explaining how gene expression and dietary components regulate genetic information. Nutrigenomics involves understanding how diet components affect gene expression, meaning which genes are induced and which are repressed against a particular nutrient [103]. Chronic diseases, such as obesity, DM2, and cancer, are expressed from complex polygenic reactions with the environment. The most influential environmental interaction in the development of these diseases is given by the consumed nutrients. Evidence of gene-nutrient interaction is substantially demonstrated, estimating that a balanced healthy nutrition reduces the overall incidence of cancer by 35%. On the other hand, polymorphisms that predispose to certain diseases have been identified under unhealthy diet; this is the case of DM2, osteoporosis, vascular disease, and others, which can be prevented by modifying the diet [104]. The regulation of gene expression is performed through specific proteins that interact with DNA through posttranscriptional or posttranslational modifications. Regulation can occur at the level of mRNA during splicing; it would result from the interaction of certain molecules with specific nutrients, whose result could be potentially preventive [104]. The diet and the GM composition have also been associated with different characteristics of the metabolic syndrome (MS) (obesity, DM2, cardiovascular diseases, and nonalcoholic steatohepatitis). Increasing evidence suggests that the GM contributes to the onset of its characteristic low-grade inflammation, through mechanisms associated with intestinal barrier dysfunction [105]. The GM of an obese person in comparison with a normal-weight person presents a greater percentage of *Firmicutes* and smaller percentage of *Bacteroidetes*, causing dysbiosis in most of the obese and/or diabetic patients (**Figure 2**). Due to its physiological impact, GM is now recognized as an organ and can be transplanted from one individual to another [106]. Recent evidence suggests that the intestinal microbiome affects nutrient acquisition, energy storage, and metabolic pathways of the host [10]. *Bacteroidetes* have been shown to easily assimilate dietary carbohydrates. In a study in mice lacking Toll-like receptors (TLRs), which are receptors that recognize important patterns of inflammation and immunity, it is shown that these mice present hyperphagia and obesity and develop metabolic syndrome, when intestinal microbiome of these

analyses of the GM of subjects suffering from DM2 allowed to identify bacterial genes that are differentially expressed in those subjects; these changes in the gene expression of microbiome are related to the metabolic dysfunction and inflammation that these patients suffer from [99]. Bacterial genes including *Clostridiales* sp. SS3/4, *Faecalibacterium prausnitzii*, *Roseburia intestinalis*, and *Roseburia inulinivorans* are decreased in patients with DM2, whereas genes corresponding to *Bacteroides* sp., *Clostridium hathewayi*, *Clostridium ramosum*, *Clostridium symbiosum*, and *Eggerthella lenta*, are increased in these subjects [100]. Functional analyses suggest enriched genes in samples of DM2 patients are involved in plasmatic membrane sugar transport, branched-chain amino acids transport, methane metabolism, xenobiotic degradation and metabolism, biosynthesis of hydrogen sulfide, and oxidative stress. In contrast, decreased genes are related to functions such as chemotaxis, flagellum assembly, butyrate biosynthesis, and the metabolism of cofactors and vitamins [100]. The depletion of bacterial strains producing butyrate in patients with DM2 may be related to the ability of this fatty acid to increase secretion of peptide similar to glucagon type 1 (GLP1) and peptide YY, whose function is to promote intestinal gluconeogenesis, which leads

**Figure 1.** Changes in the composition of the gut microbiome are associated with an increased risk of DM2: In patients with DM2, the intestinal dysbiosis causes a decrease of short-chain fatty acid content, molecules that stimulate the secretion of peptide similar to glucagon type 1 (GLP1) and YY peptide by intestinal cells, proteins that control glucose

to a better control of glucose homeostasis and cellular energy (**Figure 1**) [101, 102].

In most chronic pathologies, environmental and genetic factors are involved because of a polygenic behavior. Recent research investigate the mechanisms involved in the dysfunction of a healthy phenotype to another with chronic dysfunction, explaining how gene expression

**4. Nutrigenomics and the microbiome**

homeostasis and regulate the intake of nutrients in intestinal cells.

18 Diabetes Food Plan

**Figure 2.** The GM of an obese person in comparison with a normal-weight person presents a greater percentage of *Firmicutes* and smaller percentage of *Bacteroidetes*, causing dysbiosis in most of the obese and/or diabetic patients.

mice is transplanted to germ-free mice with the TLR5 gene intact; they also developed the *Bifidobacterium* strain similar to the metabolic syndrome, suggesting that the GM was the determinant factor of this disease phenotype [107]. Another study showed that mice deficient in TLR2 presented greater amount of *Firmicutes* and *Actinobacteria* and smaller amount of the genus *Bifidobacterium* [10, 107]. Administration of an antibiotic cocktail eliminated many of the *Firmicutes* and resulted in improved insulin action and increased glucose tolerance [107].
