**5. Prebiotics**

*Prebiotics and Probiotics - Potential Benefits in Nutrition and Health*

[76–78]. Interestingly, behavior changes in elderly have been associated with decreased immune function, resulting in alteration of intestinal microbiota-brain

*Structure of the enteric nervous system. Both plexuses can be identified (myenteric and submucosal). The extension goes from the intestinal wall to the enteric plexuses and from there to the pre-vertebral ganglia of the spinal cord and brainstem. SNS, sympathetic nervous system; PSNS, parasympathetic nervous system.*

In the first weeks of life, microbiota diversifies into a microbial community in which anaerobic microorganisms predominate [80]. This early colonization coincides with hypothalamic-pituitary-adrenal (HPA) axis activation, which has an important role in the innervation of the gastrointestinal (GI) tract and enteric nervous system (ENS) function. Likewise, the production of 5HT by enterochromaffin cells is regulated by the intestinal microbiota, inducing de *novo* synthesis of

Several reports have shown the relation between intestine and the CNS through metabolic, neuroendocrine, and immunological pathways, impacting neuronal plasticity and cognition. Production of proinflammatory cytokines (IL-1) in intestinal lumen may affect the brain through vagus nerve [81]. Also, bacterial products like lipopolysaccharide (LPS) can increase cytokines production, as well as induce both neuroinflammation and neurodegeneration [82]. In addition, it was shown that WD-fed mice had intestinal dysbiosis, which was accompanied by inflammatory signaling in the brain, microglial activation, and reduced neuroplasticity [83]. Therefore, dysbiosis of gut microbiota may increase the cytokines production and neuroinflammation, affecting mood, or it could induce psychiatric disorders such as depression and anxiety as was described in animal models [56] as well as in comparative studies performed in humans [5, 84]. Moreover, in maternal immune activation (MIA) mouse model, intestinal dysbiosis induced both higher production of both 4-ethylphenylsulfate (4EPS) and indolepyruvate, leading to autism spectrum disorder (ASD). Interestingly, with *Bacteroides fragilis* administration, these

**4.1 Dysbiosis and its effect on the neuroplasticity and behavior**

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behavioral symptoms were ameliorated [85].

connection [79].

**Figure 3.**

5HT [44].

Since its initial description in 1995, the concept of prebiotic has been in constant evolution. Currently, according to Gibson and Roberfroid, a probiotic has been defined as "any substance present in diet, which specifically stimulates the growth and/or the fermentative activity of one or a limited number of bacteria species of intestinal microbiota, generating beneficial effects on health of host as a consequence of changes on either bacterial composition or metabolic activity" [90].

Generally, a food ingredient is considered as a prebiotic when it has the following characteristics: (a) it must be kept in good condition until reaching the distal portions of the intestine; that is, it is not absorbed in the anterior part of the gastrointestinal tract and resists the hydrolysis of digestive enzymes [91] such as α-glucosidase, maltase, isomaltase, and sucrase [92]; (b) it must act as a selective substrate in the growth and/or metabolism of one or a limited number of beneficial bacterial species, such as Lactobacillus spp. and Bifidobacterium spp.; and finally (c) it must positively stimulate the microbiota, by increasing beneficial microorganisms and reducing pathogenic bacteria [93].

It is well known that proliferation of bifidobacteria and lactobacilli is favored by prebiotics; moreover, the proliferation of bacterial pathogenic strains such as *Clostridium*, *Escherichia*, *Campylobacter*, *Enterobacterium,* or *Salmonella* is inhibited. It has been proposed that intestinal microbiota is in involved in inhibition prebiotics mechanisms, by either competition for adhesion sites to the mucosa, or changes in the intestinal environment, such as (a) a reduction in pH as result of the synthesis of SCFA and (b) production of metabolites inhibiting pathogens proliferation, such as bacteriocins [94].

#### **5.1 Types and sources**

As already mentioned, prebiotics are normally ingested in the diet; however, only some carbohydrates (poly and oligosaccharides), whose chemical structure has β-type bonds, some peptides, some proteins, and certain lipids such as esters and ethers are food ingredients qualified as prebiotics [95].

Different types of oligosaccharides considered as prebiotics have been reported, among them are: fructooligosaccharides (FOS), oligofructose (OF), the inulin type fructans (ITFs), galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), and lactulose. However, there are others less known such as isomaltooligosaccharides (IMOS). Xylooligosaccharides (XOS) and mananooligosaccharides (MOS) also have a probiotic potential [90, 95]. It is well known that sucrose and starch are the main carbohydrates found in higher plants, followed by glucomannans and fructans are the main reserve sources in the vegetable kingdom [96, 97].
