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

#### **4.1 General considerations**

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 and Parkinson's disease [32].

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

The donor selection is strict and involves screening of medical history, screening for chronic diseases, and laboratory testing for pathogenic gastrointestinal infections [33].

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

The process of choosing donors include four stages as follows: stage 1, eliminating 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 antibioticresistant bacteria; and stage 4, blood tests [35, 36].

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 fecal microbiota transplant [37].

#### **4.2 FMT in inflammatory bowel disease**

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

immune system. This feature is the reason why ongoing research carries so much interest in correcting dysbiosis using fecal microbiota transplantation [37, 38].

FMT can reduce IBD's severity by increasing the production of short-chain fatty acids (butyrate); this way, the bowel permeability is reduced, and the integrity of the gut epithelium is maintained. Also, inhibiting the production of inflammatory elements, leukocyte adhesion, and the activity of T cells, FMT may restore the immune system [38].

In patients with ulcerative colitis and Crohn's disease, preliminary clinical studies showed a long-term follow-up clinical remission maintained, even endoscopic and histologic remission in a few other cases. A meta-analysis of nine studies showed a remission rate of 36.2%. Still, the results depend on some factors like age (higher remission in younger patients with ages between 7 and 20 years old), route of administration (naso-jejunal tube, enema, colonoscopy), and dose and preparation of donor feces. Also, it seems like fecal microbiota transplant is more effective in Crohn's disease than in ulcerative colitis with remission rates of 60.5 and 22%, respectively. On the other hand, a study involving 15 patients with steroid-dependent ulcerative colitis who received fecal microbiota transplant through colonoscopy showed a long-term maintained remission in 57% of cases [38–40].

Because of the lack of uniformity regarding the treatment protocols and the delivery method, it is hard to offer a solid conclusion referring to the safety and efficacy of fecal microbiota transplant in inflammatory bowel disease. If compared with the results collected in cases of recurrent *Clostridium difficile* infection (remission in about 90%), these results may look discouraging. Still, we have to keep in mind that the inflammatory bowel disease's pathogenesis is not purely driven by dysbiosis as it happens in *Clostridium difficile* infection. Following this direction, we need more randomized controlled placebo studies to clarify the role of fecal microbiota transplant in inflammatory bowel disease [40–42].

#### **4.3 Potential adverse effects of FMT**

These can be classified into short-term and long-term side effects [19].

Short-term side effects are related to the delivery method. They may include mild fever, flatulence, constipation, diarrhea, vomiting, and abdominal discomfort, but all of these usually resolve in a few weeks. In cases when FMT was administered through the naso-jejunal tube, patients presented with high fever and the rise of the C-reactive protein. When using colonoscopy, there have been reported cases of perforation, bleeding, and symptoms related to anesthesia [43].

Due to the lack of research, there are few data collected about the dominant concern regarding the safety of fecal microbiota transplant—long-term side effects. We can speculate a considerable risk for chronic diseases, involving obesity, diabetes, colon cancer, and atherosclerosis, due to the alteration of intestinal microbiota [43, 44].

#### **5. Conclusions**

Inflammatory bowel diseases are chronic, relapsing intestinal disorders, with pathogenesis not fully elucidated. Treatment disappointments are still high, despite the availability of different therapeutic options. Patients' reduced compliance, the impoverished life of quality, and the increased economic, sanitary, and social burden worldwide are still unresolved issues. For that reason, research must continue to identify more information about the intestinal microbiota, metabolic pathways, and

**135**

**Author details**

Felix Voinea1

Andra-Iulia Suceveanu1

and Adrian Paul Suceveanu1

, Irinel Parepa1

provided the original work is properly cited.

\*, Andrada Dumitru1

1 Faculty of Medicine, Ovidius University, Constanta, Romania

\*Address all correspondence to: andrasuceveanu@yahoo.com

, Anca Pantea Stoian<sup>2</sup>

2 University of Medicine and Pharmacy Carol Davila, Bucharest, Romania

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Marilena Musat1

, Laura Mazilu1

, Claudia Voinea1

,

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

microbial genes. A moving target may be the identification and isolation of an active component of the microbiota that could be the new target of therapies for inflamma-

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

All authors declare "no conflict of interest."

tory bowel diseases [44–45].

**Conflict of interest**

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

microbial genes. A moving target may be the identification and isolation of an active component of the microbiota that could be the new target of therapies for inflammatory bowel diseases [44–45].
