**4. Therapeutic approaches targeting microbiota (probiotics, prebiotics, postbiotics, and antibiotics)**

Probiotics are live microorganisms, which allocate great health advantages for the host organism when used in an appropriate quantity [113]. Probiotics induce anti-inflammatory effects, enhance or renew barrier work, promote the growth of beneficial bacteria, and inhibit the growth of pathogens [114]. Probiotics rebalance the gut microflora shifting from pro- to anti-inflammatory state [115]. Prebiotics are substrates that are selectively utilized by probiotics allocating health benefits [17]. Inulin is a prebiotic that retains microbial population, helps the epithelium barrier function, and inhibits from pathogens translocation [116]. This process leads to the treatment of functional symptoms in IBD. Postbiotics are bioactive molecules produced by probiotics [117]. There are many reports that showed some probiotics and prebiotics can be beneficial in treatment and prevention of IBD in both human and mice models [118].

In CD, evidence for prebiotics and probiotics is commonly dissatisfactory and antibiotics have moderate effects [66]. The most common strains that are used as beneficial probiotics are *Bifidobacterium* species, *Enterococcus faecium*, *Lactobacillus* strains, and *Saccharomyces boulardii*, *Bacillus* species, and *Pediococcus* [115]. The theoretical risks of probiotics on animal models of IBD in different studies are described that include systemic infections, harmful metabolic activities, extreme immune stimulation in susceptible patients, gene transfer, and gastrointestinal adverse effects [119]. Some traditional probiotics, such as the probiotic cocktail VSL# 3 (containing a mix of four *lactobacilli*, three *Bifidobacteria,* and one *Streptococcus* strain), have shown limited effect in treating CD and UC, by reducing active inflammation and recurrence [17, 66].

Some clinical trials showed that *Lactobacillus rhamnosus* administration in gastroenteritis children did not have better outcomes than those who received placebo [120]. Although a multi-strain probiotic (including *L. rhamnosus*, *Lactobacillus plantarum*, *Lactobacillus acidophilus,* and *E. faecium*) is related with lower intestinal inflammation in UC patients, but not in CD patients [121]. Besides the mentioned traditional probiotics, *Akkermansia muciniphila* and their supernatants that contain postbiotics significantly reduced the severity of colitis [17]. *F. prausnitzii* produce barrier improving immunosuppressive SCFAs, stimulate Tregs to produce IL-10, which have protective effects on the intestine [66]. In mice models, administration of *A. muciniphila* or its postbiotic reduced the infiltrating macrophages and CD8+ in clolon and inhibited colitis [122, 123].

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

These helpful microbes and their metabolites should be investigated as therapeutic determinants in treatment of IBD. Dietary substrates such as oligosaccharides and fiber are prebiotics that selectively increase the quantities of SCFA-producing commensals, blocking the AIEC epithelial adherence, and the virulence products of intestinal pathogens in IBD [66].

Probiotic engineering with emerging technologies such as as CRISPR-Cas system can be used to produce to treat untreatable chronic inflammatory conditions [115]. With increasing our knowledge about viable bacterial strains and synthetic biology tools, we can identify and characterize extra probiotic bacterial strains as potential candidates for probiotic engineering [124].

Antimicrobial agents and IBD have a complex relationship. They have hazardous influences on the homeostasis of the host microbiota, leading to a population shift described by increased *Enterobacteriaceae* and decreased Clostridia abundant, which is regarded a possible pre-IBD condition [125]. Also, IBD patients treated with antibiotics are at high risk of forming an overgrowth of pathogenic microbes including *C. difficile*, candida, and bacteriophages [126].

In addition, antibiotics are an integral part of the treatment repertoire in IBD, whereas before the period of immunomodulation and biologic therapy. The mechanisms of antibiotics in treatment of IBD are a direct effect on the gut microbiota, preferring flora that are linked with anti-inflammatory properties, e.g., Bacteroides and Firmicutes, and decreasing pathogenic microbes that are associated with inflammation, such as as Enterobacteriaceae, e.g., E. coli and Fusobacterium [75]. Furthermore, we can choose target-specific pathobiants or to manage individual microbiome in IBD patients by determining patient stool samples prior to treatment [124].

The immunological mechanisms of IBD have made great upgrades, provided novel tactics for IBD treatment. Biological agents induce and maintain clinical remission of IBD and promote mucosal curing. A number of biological agents that have been approved for the treatment of IBD are some of the TNF-*α* inhibitors such as Infliximab, Adalimumab, Certolizumab pegol, Glimumab, Etanercept, and Tocilizumab [24]. However 10–40% of IBD patients do not respond or lose their response to treatment over time [127].

#### **4.1 Fecal microbiota transplantation (FMT)**

FMT appears effective therapy for treatment of recurrent CDI and in UC or CD remission induction but remains strong and safe in the long term is not clear [128, 129]. A significant proportion of recurrent CDI patients have IBD, and FMT is moderately less successful in treatment of CDI from patients with IBD in comparison with patients without IBD [130]. Some issues could affect the FMT outcome in IBD treatment including donor choice; preparation of fecal material; clinical management, the high abundances of fungi or virus communities in donor stool or other essential necessities for implementing an FMT center [131, 132].

Recently, the field of IBD genetics has made enormous progress, and different relative molecular and cellular pathways exist. Fluctuations in specific gene loci promise therapeutics for IBD in the future. Besides, FMT, novel natural medicines, new antimicrobial agents, and combined treatment programs are also anticipated to break the IBD and therapeutically delay. The combined treatment strategies that use anti-inflammatory agents and anti-fibrotic drugs will provide great insights into the existing IBD therapeutics [17].
