**3. Microbiota**

In humans, the gut microbiota varies across the digestive tract. There are relatively few bacterial species present in the stomach and small intestine, compared to the colon, which is the habitat of the highest microbial density—up to 1012 cells per gram of intestinal content. Ninety-nine percent of the bacteria are anaerobes, except the cecum, where aerobic bacteria achieve high frequencies [21].

Although many species in the human gut have not been studied because they cannot be cultured by the ways yet discovered, there are four dominant phyla: *Proteobacteria*, *Bacteroidetes*, *Actinobacteria*, and *Firmicutes*. Most bacteria belong to the genera *Bifidobacteria*, *Clostridium*, *Peptostreptococcus*, *Bacteroides*, *Peptococcus*, *Ruminococcus*, *Eubacterium*, and *Faecalibacterium* [22, 23].

#### **3.1 Normal functions**

The gut microbiota is still intensively studied. Besides metabolizing indigestible food compounds, it stimulates the gut immune system, directly defending against pathogens. It has a substantial role in developing and maintaining the intestinal epithelium and inducing antibody production. Also, studies focused on its action in the gut-brain axis [23, 24].

#### *3.1.1 Direct inhibition of pathogenic bacteria*

The intestinal barrier provides protection against pathogenic invasion through many defense mechanisms, including butyrate and other metabolically protective products, the commensal bacteria competitively preventing pathogenic bacteria's

colonization. Disruption of intestinal barrier function may cause local or even systemic immune over-response, afferent vagus nerve activation, neuroinflammation, and mast cell degranulation. Furthermore, some species of the commensal bacteria, like *Lactobacillus plantarum*, binds and stimulates the Toll-like receptor 2 (TLR2) in the intestinal epithelium, thus maintaining epithelial integrity [24–26].

### *3.1.2 Development of the immune system*

The human intestinal flora develops in the first 2 years after birth, when the intestinal epithelium and mucosal barrier evolve in a tolerant and even in a supportive manner. Particularly, goblet cells—the ones producing the mucosa—proliferate, resulting in a thickening of the mucosa layer in which commensal bacteria may anchor and feed but cannot penetrate. Furthermore, the gut-associated lymphoid tissue, which is part of the gut epithelium, has a role in detecting and reacting to pathogens, being tolerant of commensal species and its metabolites and digestive products of food [26–29].

Cytokines stimulate the immune system to produce inflammation to protect itself, which may decrease the immune response to control homeostasis and favor healing after injuries. There is some bacterial species in the intestinal flora which seems to drive the production of selective cytokines by the immune system, such as *Bacteroides fragilis* and *Clostridium* species, which may induce an anti-inflammatory response, although some segmented filamentous bacteria cause the production of inflammatory cytokines [29, 30].

Another function of the intestinal flora is driving the immune system to produce antibodies. Thus, B cells switch class to IgA in another way, normally needing activation from T helper cells. Intestinal epithelial cells induce NF-kB signaling, which causes the secretion of further signaling molecules. These interact with B cells and induce the switching class to IgA—an important type of antibody because it keeps healthy a mucosal environment by eliminating the microorganisms that cause inflammatory responses [24, 25].

Gut flora can produce metabolites that can affect cells in the immune system, such as short-chain fatty acids produced through fermentation, and can induce an increased production of eosinophils, neutrophils, and basophils, which are components of the innate immune system and have a role in limiting the infection's spreading [26].

## *3.1.3 Metabolism*

The intestinal flora is essential for digestion through some enzymes that the human body does not possess to break down polysaccharides. Carbohydrates are turned into short-chain fatty acids by saccharolytic fermentation, including acetic acid, propionic acid, and butyric acid, used by the host cells as a source of energy and nutrients. Also, gut flora facilitates the absorption of minerals—magnesium, calcium, iron—and synthesizes vitamins, biotin and folate [27].

#### *3.1.4 Microbiome-gut-brain axis*

The microbiome-gut-brain axis includes the central nervous system and the neuroendocrine and neuroimmune systems, hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, the vagus nerve, and the intestinal microbiota [28].

The term refers to the biochemical signaling between the central nervous system and the gastrointestinal tract [29].

**133**

*Is a Fecal Microbiota Transplant Useful for Treating Inflammatory Bowel Disease?*

Dysbiosis represents microbial imbalance or maladaptation that can be caused by many triggers, such as antibiotic treatments, alcohol abuse, or inappropriate diet. Also, microorganisms present in the digestive tract may contribute to inflammatory disorders, or specific metabolites influence some signaling pathways leading to obesity and colon cancer. Additionally, sepsis may occur in cases of breaking down of the intestinal epithelium with the invasion of flora components into host's

The new key in treating dysbiosis is the fecal microbiota transplant, which restores colonic microflora. It involves the transplantation of fecal bacteria from a healthy individual by colonoscopy, enema, orogastric tube, or orally by capsules containing freeze-dried material. FMT has been used in treating *Clostridium difficile* infection and experimentally in inflammatory bowel disease, irritable bowel syndrome, constipation, and some neurological conditions, like multiple sclerosis

The size of samples has to range from 30 to 100 grams of fecal material for the treatment to be effective. The fresh stool is needed to increase the viability of bacteria, and samples are prepared within 6–8 hours, diluted with 2.5–5 times the

The donor selection is strict and involves screening of medical history, screening for chronic diseases, and laboratory testing for pathogenic gastrointestinal

However, clinical trials report cases of important adverse events after fecal microbiota transplant, such as gram-negative bacteremia combined with aspiration pneumonia or even toxic megacolon. Adverse events are the reason why the FDA decided to expand donor-stool screening by including tests for human T-lymphotropic virus, norovirus, and extended-spectrum beta-lactamase-producing microorganisms. Also, to minimize the risk of infection, clinicians should forget the "one size fits all" approach and consider the risks and benefits for each

The process of choosing donors include four stages as follows: stage 1, eliminat-

We can conclude that healthy donors are hard to find. Thus clinicians should continue improving donor screening to reduce drug-resistant microorganisms transmission, and research should focus on the benefits and the risks involved in

It is mandatory to mention the important role that dysbiosis may have in the pathogenesis of inflammatory bowel disease, considering the abnormal inflammatory response resulted from the complex relationship between microbiota and the

sample's volume with normal saline, sterile water, or 4% milk [32, 33].

individual, especially in cases of immunocompromised patients [34–36].

resistant bacteria; and stage 4, blood tests [35, 36].

fecal microbiota transplant [37].

**4.2 FMT in inflammatory bowel disease**

ing overweight (body mass index >30) patients, smokers, and those unable to donate periodically; stage 2, eliminating donors with microbiome-associated conditions, such as metabolic, gastrointestinal, autoimmune, allergic, atopic, neurologic, and psychiatric; stage 3, stool and nasal screening, involving tests for antibiotic-

*DOI: http://dx.doi.org/10.5772/intechopen.91444*

**4. Fecal microbiota transplant (FMT)**

**3.2 Dysbiosis**

compartments [30, 31].

**4.1 General considerations**

and Parkinson's disease [32].

infections [33].

*Is a Fecal Microbiota Transplant Useful for Treating Inflammatory Bowel Disease? DOI: http://dx.doi.org/10.5772/intechopen.91444*

### **3.2 Dysbiosis**

*Human Microbiome*

*3.1.2 Development of the immune system*

products of food [26–29].

inflammatory cytokines [29, 30].

cause inflammatory responses [24, 25].

spreading [26].

*3.1.3 Metabolism*

*3.1.4 Microbiome-gut-brain axis*

and the gastrointestinal tract [29].

colonization. Disruption of intestinal barrier function may cause local or even systemic immune over-response, afferent vagus nerve activation, neuroinflammation, and mast cell degranulation. Furthermore, some species of the commensal bacteria, like *Lactobacillus plantarum*, binds and stimulates the Toll-like receptor 2 (TLR2) in

The human intestinal flora develops in the first 2 years after birth, when the intestinal epithelium and mucosal barrier evolve in a tolerant and even in a supportive manner. Particularly, goblet cells—the ones producing the mucosa—proliferate, resulting in a thickening of the mucosa layer in which commensal bacteria may anchor and feed but cannot penetrate. Furthermore, the gut-associated lymphoid tissue, which is part of the gut epithelium, has a role in detecting and reacting to pathogens, being tolerant of commensal species and its metabolites and digestive

Cytokines stimulate the immune system to produce inflammation to protect itself, which may decrease the immune response to control homeostasis and favor healing after injuries. There is some bacterial species in the intestinal flora which seems to drive the production of selective cytokines by the immune system, such as *Bacteroides fragilis* and *Clostridium* species, which may induce an anti-inflammatory response, although some segmented filamentous bacteria cause the production of

Another function of the intestinal flora is driving the immune system to produce

Gut flora can produce metabolites that can affect cells in the immune system, such as short-chain fatty acids produced through fermentation, and can induce an increased production of eosinophils, neutrophils, and basophils, which are components of the innate immune system and have a role in limiting the infection's

The intestinal flora is essential for digestion through some enzymes that the human body does not possess to break down polysaccharides. Carbohydrates are turned into short-chain fatty acids by saccharolytic fermentation, including acetic acid, propionic acid, and butyric acid, used by the host cells as a source of energy and nutrients. Also, gut flora facilitates the absorption of minerals—magnesium,

The microbiome-gut-brain axis includes the central nervous system and the neuroendocrine and neuroimmune systems, hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, the vagus nerve, and the intestinal microbiota [28].

The term refers to the biochemical signaling between the central nervous system

calcium, iron—and synthesizes vitamins, biotin and folate [27].

antibodies. Thus, B cells switch class to IgA in another way, normally needing activation from T helper cells. Intestinal epithelial cells induce NF-kB signaling, which causes the secretion of further signaling molecules. These interact with B cells and induce the switching class to IgA—an important type of antibody because it keeps healthy a mucosal environment by eliminating the microorganisms that

the intestinal epithelium, thus maintaining epithelial integrity [24–26].

**132**

Dysbiosis represents microbial imbalance or maladaptation that can be caused by many triggers, such as antibiotic treatments, alcohol abuse, or inappropriate diet. Also, microorganisms present in the digestive tract may contribute to inflammatory disorders, or specific metabolites influence some signaling pathways leading to obesity and colon cancer. Additionally, sepsis may occur in cases of breaking down of the intestinal epithelium with the invasion of flora components into host's compartments [30, 31].
