**3. Microbiota and its composition**

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

have been described, however the most important are:

e.Decoupling oxidative phosphorylation.

Children Oral absorption of lead is more

capacity).

capacity). Crosses placenta.

increased compared with an adult. Deficiencies of calcium and iron increase oral absorption of lead. Children accumulate more lead in bone during the growing.

A greater amount of lead is absorbed by inhalation (increased ventilatory

In pregnancy, lead is redistributed of bone into the bloodstream by increased calcium requirement. A greater amount of lead is absorbed by inhalation (increased ventilatory

*Most important aspects to consider in the toxicokinetics of vulnerable populations.*

Crosses blood-brain barrier.

a.Production of free radicals with oxidative stress generation.

b.Enzymatic inhibition in a reversible and irreversible way.

acids and cadmium [41].

reactions.

d.Apoptosis.

acids, bile glutathione release and fecal excretion of bile acids. The biliary and fecal excretion of cadmium increased markedly after the administration of *L. plantarum CCFM8610*, which resulted in a marked reduction in Cd levels in tissues. These effects were related to the intestinal microbiota, since prior antibiotic treatment reversed the effects induced by *L. plantarum CCFM8610* on the metabolism of bile

Finally, heavy metals and some demethylated metabolites are eliminated primarily by urine, but they can also be eliminated by bile, feces, breast milk, skin, nails and hair [27, 28]. Once the processes of absorption, distribution, metabolism and elimination of heavy metals are analyzed, it is very important to consider the pharmacokinetic changes that can occur in the most vulnerable populations who suffer from toxic effects such as children and pregnant women (**Table 1**) [27]. Regarding the toxicodynamics of heavy metals, various toxicity mechanisms

c.DNA alteration probably due to the products generated in the methylation

These cell targets are primarily responsible for alterations and damage in various organs and systems [42]. Currently, the treatment for heavy metal poisoning is based on the administration of chelating drugs, which form a coordination link with heavy metal, favoring its elimination mainly by urine [27, 43]. However, when analyzing toxicodynamics, an important aspect to consider during treatment is to block the free radicals that are formed to prevent damage caused by the oxidation

**Lead Mercury Arsenic Reference**

Crosses blood-brain barrier.

Crosses placenta. Crosses blood-brain barrier.

Crosses placenta. [30, 31]

[30, 31]

**154**

**Table 1.**

Pregnant woman

In recent years, the study of intestinal microbiota has increased significantly, because important protective and metabolic functions have been associated.

In this regards, intestinal microbiota compete for nutrients, space and receptors with pathogenic microorganisms, as well as stimulating the production of antimicrobial peptides and IgA antibodies; whereas in metabolic functions, the microbiota converts many complex substances such as starches, cellulose, pectins and gums into metabolites that are easily absorbed and used by the host, it also ferments another non-digestible residues from the diet, synthesizes some vitamins and is also involved in the absorption of ions (such as calcium, magnesium and iron) and energy recovery [13, 14].

The intestinal microbiota comprised about 35,000 species of microbes and includes at least six bacteria phyla, among them *Firmicutes*, *Bacteroidetes, Fusobacteria, Proteobacteria, Actinomycetes and Verrucomicrobia*; the predominant bacteria populations constituting about 90% of the total being Firmicutes and Bacteroidetes [45]. In gastrointestinal tract, there is a wide variety of bacteria that survive and have adapted to different pH conditions. In the esophagus, pH <4 is inhabited by bacterial strains from phyla *Bacteroides, Gemella, Megasphaera, Pseudomonas, Prevotella, Rothia sps., Streptococcus and Veillonella*. The phylas such as *Streptococcus, Lactobacillus, Prevotella, Enterococcus* and *Helicobacter* reside mainly in stomach (pH = 2). In small intestine (pH = 5–7), the phylas such as *Bacteroides, Clostridium, Streptococcus, Lactobacillus, g-Proteobacteria* and *Enterococcus* are found mainly (**Figure 1**). In colon (pH = 5–5.7), *Bacteroides, Clostridium, Prevotella, Porphyromonas, Eubacterium, Ruminococcus, Streptococcus, Enterobacterium, Enterococcus, Lactobacillus, Peptostreptococcus* and *Fusobacteria* are the resident phylas and finally in cecum (pH = 5–7) the phylas such as *Lachnospira, Roseburia, Butyrivibrio, Ruminococcus, Fecalibacterium* and *Fusobacteria* are found [46]. The intestinal microbiota has both a symbiotic and mutualism relationship, and also it has an important influence on the health and physiology of host. In this way, intestinal dysbiosis has been associated with a large array of human diseases such as, irritable bowel syndrome, inflammatory bowel disease, metabolic diseases (obesity and diabetes), as well as allergic and neurological diseases [47–49].

There are several factors affecting variations on intestinal microbiota, including age and diet [46, 50, 51]. It has been suggested that intestinal microbiota in healthy individuals is relatively stable when the diet remains without major changes, but with a subtle change in diet, the intestinal bacterial composition may also change and produces important alterations on the protective barrier function of the intestine. It is well known that not only the intestinal microbiota supports the protective functions of host. In addition, there is a complex cellular barrier where a variety of cells with different functions are housed, such as enterocytes, goblet cells, enteroendocrine cells, Paneth cells and intraepithelial lymphocytes; together with the mucus

#### **Figure 1.**

*The cellular composition of the complex barrier of the small intestine, where cells with different functions, such as enterocytes, goblet cells, enteroendocrine cells, Paneth cells and intraepithelial lymphocytes are the main residents. In addition, there is a layer of mucus in the intestinal lumen. Moreover, the lamina propria contains mainly T and B lymphocytes (secretory IgA plasmatic cells), macrophages and dendritic cells. It is possible to find the following bacterial phylus in the small intestine microbiota:* Bacteroides, Clostridium, Streptococcus, Lactobacillus, g-Proteobacteria *and* Enterococcus *that adapt to survive at pH = 5–7. These bacteria are in constant contact with all host cells and they have several functions related to health and illness of host.*

and lamina propria (which consist of lymphocytes, macrophages and dendritic cells), the main function is to limit the translocation of bacteria or other antigens and, therefore, proinflammatory processes are avoided and controlled (**Figure 1**). However, some intestinal bacteria from microbiota could produce toxic metabolites that may damage the epithelial barrier, increasing intestinal permeability and allow the entry of bacterial products into the circulatory system [52].

On the other hand, the role of the microbiota in detoxification of xenobiotics and contaminants (pesticides and heavy metals) has been poorly studied. Nevertheless, it has been found that intestinal microbiota contributes to metabolism of xenobiotics [23] and heavy metals such as cadmium [21], mercury [20] and metalloids such as arsenic [24]. In this regards, in rats [53] and mice [54], several bacteria strains have been proposed and used as detoxifying probiotics, including mainly lactic acid bacteria. However, to date, there are no studies about the use of lactic acid bacteria as probiotics in humans. Recently, in *Drosophila melanogaster*, it has been found that use of *L. rhamnosus* has reduced both absorption and toxicity of organophosphate pesticides [55]. Also, lactic acid bacteria [56] and *Pediococcus* [57] have been used to reduce the toxic effects of aflatoxins and mycotoxin present in food, respectively. Likewise, in vitro experiments have shown the ability of lactic acid bacteria to bind and neutralize acrylamide molecules, a carcinogenic component present in some foods [58].

Since 1977, the interaction of the intestinal microbiota with the elimination of heavy metals was demonstrated. Here, elimination of mercury in feces of germ-free mice was lower, while the retention of mercury was slightly higher in organs from germ-free mice than in control mice [59]. In addition, it has been shown that oral administration of probiotics like *Lactobacillus plantarum* inhibit heavy metal cadmium (Cd) absorption by protecting the intestinal barrier upon

**157**

*Role of the Microbiome as the First Metal Detoxification Mechanism*

acute and chronic Cd intoxication in mice [25]. Recently, it has been proposed that the possible mechanism of detoxification of Cd upon oral administration of *Lactobacillus plantarum* as a probiotic is through the enterohepatic cycle, increasing the metabolism of bile salts, which are conjugated with Cd and favoring its elimination in feces [40]. Similarly, the probiotic strains of *Lactobacillus rhamnosus*, *Propionibacterium freudenreichii* and *Shermanii js.* showed an effective ability to bind cadmium and lead, both in vitro and in experimental mouse model of oral heavy metal intoxication [60, 61]. Additionally, use of probiotics improved the nutritional, biochemical and physiological parameters in experimental rat model intoxicated with chromium, suggesting that probiotic bacteria neutralize the toxic effects of chromium [62]. Also, administration of *Lactobacillus plantarum* as a probiotic significantly reduced both renal and hepatic injury induced by aluminum in mice that are chronically exposed to this toxic heavy metal [63]. Recently, human gut commensal *Faecalibacterium prausnitzii* was used as probiotic in mice. Here human stool transplantation restored protection in acute arsenic toxicity in mouse models [24]. Moreover, the functions in detoxification of inorganic arsenic of arsDABC genes from obligate anaerobic bacteria *Bacteroides vulgatus*, a common resident of the human microbiota have been well characterized [64]. Interestingly, in a clinical pilot study, yogurt supplemented with probiotic was administered to pregnant women and school children living in contaminated areas of Tanzania, resulting in a significant reduction on blood levels of heavy metals such as mercury

Finally, the ability of the microbiota to metabolize drugs has been referred as Pharmacomicrobiomics [66]. Intestinal microbiota generates phase I and phase II reactions to metabolize drugs, similar to the one generated by host cells. These include hydrolysis, dealkylation, glucuronidation and others reactions [67]. Thus, it has been strongly suggested that bacteria from the intestinal microbiota produce enzymes that metabolize drugs and contribute to determine the pharmacological properties of several drugs. Some examples of drugs that are metabolized by intestinal microbiota include aminosalicylates and anthranoid laxatives; digoxin; irinotecan and non-steroidal anti-inflammatory drugs, such as rutin, diosmin and baicalin, as well as l-dopa and simvastatin, used for the treatment of Parkinson's

Guanajuato is a Mexican state located in the middle area of the country and according to the 2015 intercensal National Population Census, Guanajuato has 5,853,677 inhabitants, representing 4.9% of the total population of the country. Guanajuato is divided into 6 socioeconomic and geographic regions with 46 municipalities [71]. Since 2005, the risks of arsenic exposure in drinking water have been studied in some rural populations belonging to the State of Guanajuato [72]. In a comparative study in children of 10 years of age on average, arsenic levels were found in hair above the norm (from <0.006 to 1.3 mg/kg) and for the control group <0.006 mg/kg of arsenic [72]; however, it was found that children with non-standard levels of arsenic in hair, referred to drinking only carafe water and not tap water, which was explained because the water used to prepare soups, broths or beans, was used tap water [73]. On the other hand, only 26% had an adequate energy intake and the consumption of protein, folic acid, zinc and fiber was low according to RDA and children used to have mainly soft drinks, fried foods and processed foods [74]. Another study was applied in 352 households (heads of family) and measuring experiences related to access to water [sufficiency, safety (safety),

*DOI: http://dx.doi.org/10.5772/intechopen.89232*

and arsenic [65].

disease [68–70].

**4. Evidence in the state of Guanajuato, Mexico**

### *Role of the Microbiome as the First Metal Detoxification Mechanism DOI: http://dx.doi.org/10.5772/intechopen.89232*

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

and lamina propria (which consist of lymphocytes, macrophages and dendritic cells), the main function is to limit the translocation of bacteria or other antigens and, therefore, proinflammatory processes are avoided and controlled (**Figure 1**). However, some intestinal bacteria from microbiota could produce toxic metabolites that may damage the epithelial barrier, increasing intestinal permeability and allow

*The cellular composition of the complex barrier of the small intestine, where cells with different functions, such as enterocytes, goblet cells, enteroendocrine cells, Paneth cells and intraepithelial lymphocytes are the main residents. In addition, there is a layer of mucus in the intestinal lumen. Moreover, the lamina propria contains mainly T and B lymphocytes (secretory IgA plasmatic cells), macrophages and dendritic cells. It is possible to find the following bacterial phylus in the small intestine microbiota:* Bacteroides, Clostridium, Streptococcus, Lactobacillus, g-Proteobacteria *and* Enterococcus *that adapt to survive at pH = 5–7. These bacteria are in constant contact with all host cells and they have several functions related to health and illness of host.*

On the other hand, the role of the microbiota in detoxification of xenobiotics and contaminants (pesticides and heavy metals) has been poorly studied.

Nevertheless, it has been found that intestinal microbiota contributes to metabolism of xenobiotics [23] and heavy metals such as cadmium [21], mercury [20] and metalloids such as arsenic [24]. In this regards, in rats [53] and mice [54], several bacteria strains have been proposed and used as detoxifying probiotics, including mainly lactic acid bacteria. However, to date, there are no studies about the use of lactic acid bacteria as probiotics in humans. Recently, in *Drosophila melanogaster*, it has been found that use of *L. rhamnosus* has reduced both absorption and toxicity of organophosphate pesticides [55]. Also, lactic acid bacteria [56] and *Pediococcus* [57] have been used to reduce the toxic effects of aflatoxins and mycotoxin present in food, respectively. Likewise, in vitro experiments have shown the ability of lactic acid bacteria to bind and neutralize acrylamide molecules, a carcinogenic compo-

Since 1977, the interaction of the intestinal microbiota with the elimination of heavy metals was demonstrated. Here, elimination of mercury in feces of germ-free mice was lower, while the retention of mercury was slightly higher in organs from germ-free mice than in control mice [59]. In addition, it has been shown that oral administration of probiotics like *Lactobacillus plantarum* inhibit heavy metal cadmium (Cd) absorption by protecting the intestinal barrier upon

the entry of bacterial products into the circulatory system [52].

**156**

**Figure 1.**

nent present in some foods [58].

acute and chronic Cd intoxication in mice [25]. Recently, it has been proposed that the possible mechanism of detoxification of Cd upon oral administration of *Lactobacillus plantarum* as a probiotic is through the enterohepatic cycle, increasing the metabolism of bile salts, which are conjugated with Cd and favoring its elimination in feces [40]. Similarly, the probiotic strains of *Lactobacillus rhamnosus*, *Propionibacterium freudenreichii* and *Shermanii js.* showed an effective ability to bind cadmium and lead, both in vitro and in experimental mouse model of oral heavy metal intoxication [60, 61]. Additionally, use of probiotics improved the nutritional, biochemical and physiological parameters in experimental rat model intoxicated with chromium, suggesting that probiotic bacteria neutralize the toxic effects of chromium [62]. Also, administration of *Lactobacillus plantarum* as a probiotic significantly reduced both renal and hepatic injury induced by aluminum in mice that are chronically exposed to this toxic heavy metal [63]. Recently, human gut commensal *Faecalibacterium prausnitzii* was used as probiotic in mice. Here human stool transplantation restored protection in acute arsenic toxicity in mouse models [24]. Moreover, the functions in detoxification of inorganic arsenic of arsDABC genes from obligate anaerobic bacteria *Bacteroides vulgatus*, a common resident of the human microbiota have been well characterized [64]. Interestingly, in a clinical pilot study, yogurt supplemented with probiotic was administered to pregnant women and school children living in contaminated areas of Tanzania, resulting in a significant reduction on blood levels of heavy metals such as mercury and arsenic [65].

Finally, the ability of the microbiota to metabolize drugs has been referred as Pharmacomicrobiomics [66]. Intestinal microbiota generates phase I and phase II reactions to metabolize drugs, similar to the one generated by host cells. These include hydrolysis, dealkylation, glucuronidation and others reactions [67]. Thus, it has been strongly suggested that bacteria from the intestinal microbiota produce enzymes that metabolize drugs and contribute to determine the pharmacological properties of several drugs. Some examples of drugs that are metabolized by intestinal microbiota include aminosalicylates and anthranoid laxatives; digoxin; irinotecan and non-steroidal anti-inflammatory drugs, such as rutin, diosmin and baicalin, as well as l-dopa and simvastatin, used for the treatment of Parkinson's disease [68–70].
