**6. Conclusions**

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].

Some studies have shown the clear connection between immune system and neuroendocrine system highlighting the effect of the GM, which allows a new focus for research on the so-called brain gut axis [12]. The mechanisms of enteric neuroprotection were recently been described; enteric neurons have one of their own signaling molecules to this propose. In the adult intestine, serotonin acts like a paracrine signal hormone and neurotransmitter [108]. However, it is also a neuronal growth factor during development and a major promoter of mucosal epithelium growth by stimulating submucosal cholinergic neurons [109]. This neurotransmitter may even stimulate neurogenesis in the growing enteric nervous system, and in adults, this hormone promotes neurogenesis and neuroprotection through the activation of 5-HT4 receptors. It is interesting to mention that mucosal serotonin is not a direct neuroprotective agent to enteric neurons. Mucosal serotonin behaves as a pro-inflammatory factor, and this ability constitutes a threat to neuronal survival [110]. According to these facts, this hormone has received the name of "sword and shield" of the intestine. Mucosal serotonin is the pro-inflammatory "sword," while neuronal serotonin is the anti-inflammatory "shield" [111]. It has been demonstrate that DM1 is related with an excess of pro-inflammatory cytokines close to B pancreatic cells, while DM2 is caused due to an excess of pro-inflammatory cytokines in systemic circulation, which could be related to intestinal serotonin secretion. Gershon et al. have established that neurodegenerative/neuroprotective actions of 5-HT4 receptor complex may be vital for the normal enteric nervous system's maintenance [12]. Bianco et al. show the mechanisms through the 5-HT4 agonist participate in protection of enteric neurons against oxidation [112]. This sentence is relevant because the enteric neurons lost during inflammation strongly depend on the released forces throughout oxidative stress (**Figure 3**) [113, 114]. Bhattarai et al. suggest that the "sword" function is manipulated by the microbiome [115]. The intestine has a variety of regulatory mechanisms that contrast the actions of 5-HT for transport maintenance; conversely, Chang and Rao incorporate the GM as a homeostasis influence factor evading the alteration of 5-HT during diarrhea and intestine inflammatory diseases. Recently, observations have been made about the possible mechanisms by which dysbiosis of the microbiome alters the function of 5-HT [14]. The HIM plays a key role in enhancing the serotonin biosynthesis in enterochromaffin cells. This increased serotonin content stimulates the intrinsic projections of the primary afferent neurons and in turn activates interneurons, which activate the peristaltic reflex promoting intestinal motility and besides accelerate the gastric emptying, which is augmented when 5-HT receptor is antagonized [111]. The intestinal speedup promotes the production of several gastrointestinal hormone secretions that mediate glucose metabolism, unleashing

**5. New brain gut axis, serotonin production, and its relationship** 

**with DM**

20 Diabetes Food Plan

The interaction of the diet in the modification of HIM, in addition to its potential effect on the microbiome and the development of DM, has been positively affected by the evolution of nutrigenomics as a science discipline. Diets rich in carbohydrates and fats, favor the development of bacteria capable of causing intestinal dysbiosis of low degree of inflammation; affecting the permeability of the intestinal mucosa. It has been shown that intestinal production of serotonin by enterochromaffin cells participates in the cascade of stimulation of the proliferation of pancreatic β cells, via the lactate pathway, suggesting the hypothesis of a possible link between serotonin, insulin resistance, and DM2. Finally, the advances reflected in this chapter demonstrate a small part of the future projection around nutrigenomics and its effect on the composition of the microbiome in diabetic subjects; it would be interesting to carry out more specific studies of this area, associating it with the effect of satiety and the alteration of the microbiome in patients with obesity and/or metabolic syndrome, as an integral part in the prevention of DM2.

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