**3. IBD and gut microbiota**

IBD is obviously related to gut dysbiosis that impairs host-microbe and immune homeostasis [53]. The human gut includes trillions of commensal bacteria per gram of gut lumen content. These bacteria can be nutritious and provide the intestinal epithelium [38, 54]. The gut microbiota leads to intestinal homeostasis due to our physiological procedure and metabolites [55]. There are different phyla, including Bacteroidetes, Firmicutes, Proteobacteria (*Escherichia* and *Helicobacter*), and Actinobacteria that include fungi, protists, and viruses (**Table 2**) [56, 57].

Ecological factors, such as as host diet, hygiene, antibiotic consumption, and lifestyle, induce immune responses that change the intestinal microbiota and damage the mucosal barrier [38, 58]. Gut microbiota plays an important role in the pathogenesis of IBD and impacts energy metabolism host, immune homeostasis, development and maintenance of mucosal integrity [24]. **Table 3** shows the effect of gut microbiota in inflammatory bowel disease and its interdependence with the immune response.

For example, *Clostridium* cluster IV and XIVa were less abundant in IBD patients than in healthy controls [55]. Bacteroides genus is obligate anaerobe bacteria and consists a large amount of the normal gut microbiota. *B. fragilis* decreases in IBD patients and promotes the quantities of anti-inflammatory cytokines against colitis [24, 75]. The overgrowth of *Enterobacteriaceae, Pseudomonas*-like bacteria, and *Escherichia coli* promotes the intestinal inflammation and alters the composition of

*Gut Microbiota and Inflammatory Bowel Disease DOI: http://dx.doi.org/10.5772/intechopen.105842*


#### **Table 2.**

*Microbiota changes associated with inflammatory bowel disease.*

the microbiota in most colitis models and IBD patients [58, 76, 77]. *Faecalibacterium prausnitzii* secret anti-inflammatory cytokines, which reduce in the intestine of IBD patients [24, 55]. *Fusobacterium* and *Ruminococcus gnavus* have also been increased in CDI patients [78]. In a recent study performed on IBD patients, a functional gut microbiome dysbiosis and impaired microbial transcript were seen. Facultative anaerobes were raised at the expense of obligate anaerobes [79]. Other different studies showed that the diversity of gut microbiota was either decreased or equal in IBD patients versus controls. *F. prausnitzii*, *Eubacterium rectale,* and *Akkermansia* were decreased, and *Actinomyces*, *Veillonella,* and *E. coli* were increased in patients with UC (**Table 3**) [80].

Other possible pathogens in the exacerbation of the IBD disease are *Mycobacterium avium* subspecies *paratuberculosis*, *Clostridium difficile*, *Listeria monocytogenes*, and Campylobacter *concisus*, as well as viruses, including *cytomegalovirus, Epstein-Barr virus,* and measles virus [17, 81]. In addition, a number of pathogenic parasites may involve in the progression of this disease. Overexposure of immune system in the presence of too many bacterial materials could also cause the loss of immunological tolerance to the bacteria, which are generally considered the normal flora in the gut [81]. Some of the individual bacterial species that associate with human IBD are reviewed here.

#### **3.1 Clostridioides difficile**

*C. difficile* is an obligate anaerobic Gram-positive spore-forming bacterium, which is prevalent in nature and also colonizes the human intestinal tract [81, 82]. *C. difficile* leads to diarrhea and colitis, frequently in persons who have been treated with antibiotics for other medical complications [81, 83, 84].

*C. difficile* can produce toxins type A and B, and IBD patients with *C. difficile* infections (CDI) appear severe clinical symptoms, such as abdominal pain, diarrhea, bloody stools, and leukocytosis [85, 86].


#### **Table 3.**

*Gut microbiome in inflammatory bowel disease and its associations with the immune system [7].*

CDI causes relapsed IBD, and IBD patients in remission had a significantly higher presence of toxigenic *C. difficile* in their intestinal tract as compared with healthy controls [87]. UC patients have a high risk of CDI in comparison with healthy population or CD patients.

The two toxins encoded by *tcdA* and *tcdB* genes lead to the disruption of epithelial cytoskeleton and tight junctions, which contribute to the CDI [81, 88, 89]. A reduction in butyrate-producing bacteria and increase in lactic-acid-producing bacteria were seen in CDI status. Overrepresentation of *Akkermansia* may be a predictive marker for the development of nosocomial diarrhea, which can result in a worse CDI prognosis [82]. Activation of the production of multiple inflammatory cytokines such *Gut Microbiota and Inflammatory Bowel Disease DOI: http://dx.doi.org/10.5772/intechopen.105842*

as IL-8, TNF-a, IL-1, and tumor necrosis factor (TNF-a) could damage the intestinal epithelial cells and trigger IBD in CDI patients [90]. Reduced bile salts happen in the colon of patients with IBD leading to spore germination of C. difficile [86, 91]. Patients with IBD present common infections such as gastrointestinal infections of *C. difficile, Salmonella, Shigella,* and *Campylobacter jejuni* [81, 92].

#### **3.2** *M. avium* **subspecies** *paratuberculosis*

*M. avium* species is commonly present in the environment and comprises four subspecies, including *M. avium* subspecies *avium, M. avium, M. avium* subspecies *hominissuis,* and *M. avium* subspecies *silvaticum* [93]. *M.avium* causes production of some inflammatory cytokines in IBD patients [86]. In IBD patients, the increase in metalloprotease leads to dysregulation in immune system and large level of inflammatory cytokines [94, 95]. Combination of multiple antibiotics including rifabutin, clofazimine, and clarithromycin, adds up to ciprofloxacin, metronidazole, or ethambutol, which are used for treatment of patients with positive different species of *M.avium* [96]. Also antibiotics such as nitroimidazoles and clofazimine are effective in the treatment of CD [97].

#### **3.3** *Helicobacter pylori*

Helicobacter species are Gram-negative bacteria. H. pylori is an important pathogen that isolates from gastrointestinal tract of humans and animals. H. pylori infection has been reported in IBD patients and shows a protective effect in IBD [98, 99]. H. pylori increases the expression of forkhead box P3 (FOXP3) with stimulating of the regulatory T cells production, reduces the production of inflammatory cytokines, and finally, decreases inflammation [100, 101]. H. pylori with cytotoxin-associated gene A (CagA+) genotype, in IBD patients, diverts TH1 response to TH2 response that has anti-inflammatory task [102].

Helicobacter species are more detected in intestinal biopsies of patients with CD and UC than controls, although this difference was not significant [103]. Molecular studies detected non-pylori Helicobactor by Helicobacteriaceae family-specific PCR in 3% of IBD patients and 8% controls [104].

#### **3.4** *C. concisus* **and** *Fusobacterium nucleatum*

Most strains of campylobacter colonize in the intestinal tract, but the colonization of *C. concisus* is in the oral cavity [105]. *C.concisus* is associated with IBD in the adult patients [106]. The virulence factors of *C. concisus* infect the lower parts of the intestinal tract [86]. Zonula occludens toxin (Zot) is expressed through a CON-Phi2 prophage and leads to the permeability of the epithelial cells and formation of IBD. This mechanism is similar to the *Vibrio cholerae* toxin [107]. *C. concisus* breaks the intestinal epithelial barrier and leads to apoptosis in human intestinal epithelial and intestinal inflammation [108]. The invasive strains of *C. concisus* enable them to survive in harsh conditions such as in anaerobic conditions [86].

*F. nucleatum* is an anaerobe bacterium that colonizes the oral cavity and intestinal tract [81]. It is abundant in intestinal tract of UC and IBD patients, and the quantity was linked with disease severity [109]. *F. nucleatum* leads to the damage of intestinal epithelium and promotes intestinal inflammation by inducing autophagic epithelial cell death [86].

#### **3.5 Adherent-invasive** *E. coli*

Adherent-invasive *E. coli* (AIEC) is a commensal human gut bacterium and is associated with ileal CD in the adult population. AIEC strains can adhere to and invade intestinal epithelial barrier assessed [110]. AIEC strains have various mechanisms and virulence factors, which are involved in the pathogenesis of IBD patients [86]. Several factors such as type 1 pili adhesion FimH and carcinoembryonic antigen cell adhesion molecule 6 are associated in promoting inflammation [111]. AIEC strains induced production of cytokines such as IL-8, TNF-a, and IL-6 in both epithelial cells and macrophages. Replication of AIEC in macrophages did not cause macrophage death, but increased production of TNF-a and IL-6 [81, 112].
