**3. Microbiome association with diseases**

As described above microorganisms present in the gut of the living organisms contribute to health or cause disease of these organisms by interplay with their immune system. Microbiome is developed at birth according to host interaction but later it is evolved and modified by surrounding factors like environmental and diet. The variation in genetic expression of different individuals is thought to be linked with different microbial composition [57]. Genotype of the host affects the composition of gut microbes. Even mutation of a single gene can cause modification in the structure of gut microbiota. The exact mechanism of association between

the gut microbes and the genotype of host is still unknown. Bifidobacteria are highly prevalent beneficial bacteria in gut microbiome and are associated with lactase non-persistent genotype. This genotype is responsible for the synthesis of lactase enzyme which helps to digest the lactose, present in the milk. Absence of this enzyme leads to lactose intolerance in different organisms. So it is important to investigate susceptibility of different underlying pathological conditions by studying microbiomes association with genotype and environmental factors that vary among different human populations [58].

Different studies showed that metabolic disorders are largely congenital and are associated with different microbiomes. For example, gut microbiomes have been linked to metabolic disorders and obesity [59].

#### **3.1 Gut microbes and gastrointestinal tract (GIT) diseases**

In gut microbiome, dysbiosis (imbalance of microbial flora) can be induced by host factors and/or external factors such as the intake of antibiotics, mental and physical stress, and nutrients in the diet. Dysbiosis is likely to impair the regular gut microbiota and the appearance of pathobionts and the production of metabolites which may be dangerous to the host or may deregulate beneficial microbial-derived metabolites. The microbial symbiosis has a significant role in the development of many diseases [60] such as the gastrointestinal diseases [61, 62], infections [63], metabolic disorders, liver diseases [64], autoimmune diseases [65], mental or psychological diseases [66] and respiratory diseases [67].

#### *3.1.1 Inflammatory bowel disease*

The inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has for quite some time been suspected to be a host reaction to its gut microbiota. CD represents the chronic inflammation of the GIT (involving any part from mouth to anus) with idiopathic etiology while UC is the chronic inflammation of the large bowel of the GIT with no known cause. Numerous aspects of the microbiota's association in IBD have been inspected in recent years. About 10–20% of adults and adolescents worldwide are affected by IBD [68]. The precise cause of IBD is unidentified, but it is believed to be a multifactorial disease. Inflammation, infection, visceral hypersensitivity, immunity, genetic factors, motor dysfunction of the GIT as well as psychopathological factors are suspected to play a role in its development [69]. Moreover, abnormal gut microbiota has been noticed in the IBD patients and in animals with intestinal inflammatory disease [70–73]. Some of the metabolically active anaerobic bacteria in the colon and terminal part of ileum interact with the immune system of epithelium and mucosal layer of the host intestine. Continuous stimulation of these microbial antigens promote pathogenic immune responses and may cause defects in the barrier functions of mucous layer by killing some beneficial bacteria or by immune dysregulation, consequently resulting in UC and CD. Moreover, disrupted microbiota structure and function in inflammatory bowel disease intensify the immune response of the host causing dysfunction of epithelium and increased permeability of the mucous layer of the intestine [74].

It is difficult to identify a single factor responsible of IBD; however, several observations have demonstrated a change in the gut microbial composition in IBD patients, both CD and UC [70]. Even though the gut microbiota has been recognized as responsible for the IBD establishment in non-predisposed hosts, numerous researches have revealed a high rate of pathogenic *E. coli* in ileal biopsies of CD patients [74]. *Mycobacterium avium* subspecies *paratuberculosis* is another bacterial

**181**

*Gut Microbiome: A New Organ System in Body DOI: http://dx.doi.org/10.5772/intechopen.89634*

are the reason or the result of the disease.

*3.1.2 Gastric cancer*

ism communication [79, 80].

forming a tumor-advancing environment.

**3.2 Role of gut microbiota in cardiovascular diseases**

approach for treating atherosclerotic cardiovascular diseases [87].

*3.1.3 Colorectal cancer*

progression [82].

species that has been commonly associated with the CD etiology [75]. Also, in IBD patients, large quantity of *Enterobacteriaceae* and a decline in *Faecalibacterium prausnitzii* was demonstrated to be related to the CD confined to the ileum [76]. However, it is not yet clear whether the IBD-related changes in the gut microbiota

For gastric cancer, *H. pylori*-associated chronic inflammation is considered as a risk factor and WHO has classified *H. pylori* as a class I carcinogen. In about 660,000 new cases every year of gastric cancer, *H. pylori* infection is identified as the major cause leading to the acid-producing parietal cells loss, and thereby prompting the gastric atrophy, metaplasia, dysplasia, and finally the formation of carcinoma [77]. The *H. pylori* elimination before the chronic atrophic gastritis may defend against gastric cancer [78]. The cancer-causing risk might be identified with the phylogenetic source of the *H. pylori* strain, host reaction, and host-microorgan-

Worldwide, the colorectal cancer (CRC) is the fourth most common cause of death associated with cancer [81]. Like other cancers, the CRC is a complex disease related to environmental and genetic factors. Ongoing research has proposed that gut microbiota assumes a role in the convergence of these factors, likely through

In certain studies, by using a germ-free mice model of adenomatous polyposis coli (APC), a markedly reduced incidence of colonic tumor and a lower tumor load was revealed when compared to normally raised mice. Further other distinct CRC phenotypes such as bleeding from rectum and iron deficiency has also been shown with an invasion of inflammatory cells emerging from an intestinal epithelial barrier dysfunction. Therefore, it seems that the microbiome and host factors (for example, age and genetic predisposition) are important to the CRC growth and

Cardiovascular and metabolic disorders are collectively known as cardiometabolic diseases and are associated with high morbidity and mortality along with significant health care expenditures [83]. The gut-derived and endogenously produced endotoxins including indoxyl sulfate, *para*-cresyl sulfate and lipopolysaccharides have been found to be involved in the development of pathological conditions ranging from atherosclerosis to cardio-renal failure or dysfunction [84, 85]. Furthermore, the development of some complex metabolic disorders including insulin resistance and obesity is also associated with differences in the composition of gut microbiota [86]. The metabolites L-carnitine, choline and phosphatidylcholine are metabolized by intestinal microbiota to generate TMA (trimethylamine) which then undergoes oxidation in liver to produce the proatherogenic metabolite known as TMAO (trimethylamine-N-oxide). Moreover, in atherosclerotic plaques was detected bacterial DNA of the intestinal microbiome indicating the direct involvement of intestinal microbiota in the development of atherosclerosis. Therefore, inhibition of intestinal microbiota-mediated TMAO production through dietary modulation has been suggested as a potential

species that has been commonly associated with the CD etiology [75]. Also, in IBD patients, large quantity of *Enterobacteriaceae* and a decline in *Faecalibacterium prausnitzii* was demonstrated to be related to the CD confined to the ileum [76]. However, it is not yet clear whether the IBD-related changes in the gut microbiota are the reason or the result of the disease.

### *3.1.2 Gastric cancer*

*Parasitology and Microbiology Research*

among different human populations [58].

linked to metabolic disorders and obesity [59].

**3.1 Gut microbes and gastrointestinal tract (GIT) diseases**

psychological diseases [66] and respiratory diseases [67].

*3.1.1 Inflammatory bowel disease*

of the mucous layer of the intestine [74].

the gut microbes and the genotype of host is still unknown. Bifidobacteria are highly prevalent beneficial bacteria in gut microbiome and are associated with lactase non-persistent genotype. This genotype is responsible for the synthesis of lactase enzyme which helps to digest the lactose, present in the milk. Absence of this enzyme leads to lactose intolerance in different organisms. So it is important to investigate susceptibility of different underlying pathological conditions by studying microbiomes association with genotype and environmental factors that vary

Different studies showed that metabolic disorders are largely congenital and are associated with different microbiomes. For example, gut microbiomes have been

In gut microbiome, dysbiosis (imbalance of microbial flora) can be induced by host factors and/or external factors such as the intake of antibiotics, mental and physical stress, and nutrients in the diet. Dysbiosis is likely to impair the regular gut microbiota and the appearance of pathobionts and the production of metabolites which may be dangerous to the host or may deregulate beneficial microbial-derived metabolites. The microbial symbiosis has a significant role in the development of many diseases [60] such as the gastrointestinal diseases [61, 62], infections [63], metabolic disorders, liver diseases [64], autoimmune diseases [65], mental or

The inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has for quite some time been suspected to be a host reaction to its gut microbiota. CD represents the chronic inflammation of the GIT (involving any part from mouth to anus) with idiopathic etiology while UC is the chronic inflammation of the large bowel of the GIT with no known cause. Numerous aspects of the microbiota's association in IBD have been inspected in recent years. About 10–20% of adults and adolescents worldwide are affected by IBD [68]. The precise cause of IBD is unidentified, but it is believed to be a multifactorial disease. Inflammation, infection, visceral hypersensitivity, immunity, genetic factors, motor dysfunction of the GIT as well as psychopathological factors are suspected to play a role in its development [69]. Moreover, abnormal gut microbiota has been noticed in the IBD patients and in animals with intestinal inflammatory disease [70–73]. Some of the metabolically active anaerobic bacteria in the colon and terminal part of ileum interact with the immune system of epithelium and mucosal layer of the host intestine. Continuous stimulation of these microbial antigens promote pathogenic immune responses and may cause defects in the barrier functions of mucous layer by killing some beneficial bacteria or by immune dysregulation, consequently resulting in UC and CD. Moreover, disrupted microbiota structure and function in inflammatory bowel disease intensify the immune response of the host causing dysfunction of epithelium and increased permeability

It is difficult to identify a single factor responsible of IBD; however, several observations have demonstrated a change in the gut microbial composition in IBD patients, both CD and UC [70]. Even though the gut microbiota has been recognized as responsible for the IBD establishment in non-predisposed hosts, numerous researches have revealed a high rate of pathogenic *E. coli* in ileal biopsies of CD patients [74]. *Mycobacterium avium* subspecies *paratuberculosis* is another bacterial

**180**

For gastric cancer, *H. pylori*-associated chronic inflammation is considered as a risk factor and WHO has classified *H. pylori* as a class I carcinogen. In about 660,000 new cases every year of gastric cancer, *H. pylori* infection is identified as the major cause leading to the acid-producing parietal cells loss, and thereby prompting the gastric atrophy, metaplasia, dysplasia, and finally the formation of carcinoma [77]. The *H. pylori* elimination before the chronic atrophic gastritis may defend against gastric cancer [78]. The cancer-causing risk might be identified with the phylogenetic source of the *H. pylori* strain, host reaction, and host-microorganism communication [79, 80].
