Fecal Microbiota Transplantation (FMT) is the introduction of a variety of microbial flora prepared from a healthy donor’s stool. Recipient’s intestine for the treatment of diseases. The solution prepared from feces scan be administered with a colonoscope, enema or capsule. FMT takes its place among clinical applications as an alternative method in the treatment of various diseases such as Parkinson’s disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, IBS and autism. Furthermore, it has proven high success rate for recurrent Clostridium Difficile Infection. The gut microbiota, most found in the large intestine, is an “invisible organ” of the human body that is important for health. The gut microbiota begins to mature at the age of 2-3 years. It varies according to geographical region and age. Firmicutes, Proteobacteria and Bacteroidetes are the most abundant phyla. They make up 95% of the sequences while Fusobacteria, Actinobacteria, Tenericutes, Verrucomicrobia, Synergistetes and Cyanobacteria each make up 0.1-5% of the sequences in a healthy environment. The balance of the gut microbiota can be disrupted by many factors, including medications, diet, diseases and vaccination. Functions of microbiota;
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Breaks down food and synthesizes nutrients
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Plays an important role in the immune system
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Provides colonization resistance
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Protects against epithelial damage
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Supports angiogenesis
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Fat storage
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Modulates human bone mass density
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Alters the nervous system
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Metabolizes therapeutic agents to active compounds
Research has suggested that gut microbiome has a significant relation with extra-intestinal disorders for instance;
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Intestinal disorders and diseases
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To obesity and various metabolic dysfunctions
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Neuropsychiatric changes and diseases
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Autoimmune diseases
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Tumor development
Improving gut microbiota is seen as one of the most impactful ways to contribute human health. Restoring the gut microbiota with fecal microbiota transplantation (FMT), has attracted great interest in recent years and took its place among the one of the most effective treatments of CDI. In this review, we will summarize the relationship between the gut microbiota and intra-intestinal or extra-intestinal disorders followed by current clinical use or emerging applications of FMT in recent years.
CLOSTRIDIUM DIFFICILE INFECTION Clostridium difficile is a gram-positive bacterium that lives in the human intestine. Prolonged use of antibiotics or hospitalizations causes them to grow and colonize. C. difficile is the most important cause of antibiotic-associated diarrhea and colitis. It is a kind of disease that is caused by toxins secreted by bacteria, causing widespread diarrhea. Many studies conducted today have proven that FMT is effective on recurrent clostridium difficile infection. According to the 2016 European clinical practice FMT consensus conference, FMT has been accepted as a therapeutic option for both mild and severe clostridium difficile infection. INFLAMMATORY BOWEL DISEASE It is a type of disease that causes inflammation in the digestive system, but especially in the intestines. it is a chronic inflammatory disease that causes great damage to the structure of the intestines. In this disease, a decrease in microbial diversity in the gut is observed. The increase and decrease in the numbers of the bacterias are noteworthy. There are two types; Crohn’s and Ulcerative Colitis. The clinical picture of Inflammatory Bowel Disease is characterized by diarrhea, abdominal pain, blood in the stool, inflammation and slimy structure, weight loss, fever and changing general health status.
Crohn’s Disease It is a chronic inflammatory disease that usually affects the small intestine and rarely the large intestine, and can be seen anywhere in the gastrointestinal tract. Symptoms vary according to the location of the inflammation. Ulcerative Colitis It is an inflammatory disease of the large intestine. It starts localized to the last region of the large intestine, but if not treated in time, it progresses to upper parts of the large intestine. Diarrhea, abdominal pain, bloody or mucous stools are among the most common symptoms. FMT was performed on an idiopathic ulcerative colitis patient in 1988 and improvement was seen. In addition, in another 6-case ulcerative colitis study, patients experienced improvement after the application. In the meta-analysis study, it was observed that 63% of ulcerative colitis patients recovered completely, and 76% were able to stop using the drug. FMT, which has been researching since 1988, is currently used in treatment of inflammatory bowel disease.
IRRITABLE BOWEL SYNDROME (IBS) It is also used for irritable bowel syndrome and spastic colon. Abdominal cramps, gas, bloating, pain, diarrhea, and constipation symptoms are seen. It is a very common disease today, affecting 15% of people. It is a disease that requires a long process to be treated and needs to be managed well. Many studies reveal that it developed as a result of decreased biodiversity. Bacteroidetes increase triggers the disease. FMT offers a promising microbiome therapy for patients with irritable bowel syndrome. METABOLIC DISEASES Metabolic syndrome is defined as a combination of overweight, fat-cholesterol metabolism disorders, high blood pressure, and sugar metabolism disorders (hidden sugar problems) that predispose to the formation of cardiovascular diseases and diabetes. In a study of mice, it was observed that microbiota from lean mice could reduce fat gain in obese recipient mice. A study showing an increase in insulin sensitivity with the FMT technique is also included in the literature.
CHRONIC RENAL DISEASE It is characterized by progressive loss of kidney function over a long period of time. As these losses increase, there is a life-threatening risk that also affects other organs. The social lives of the patients are adversely affected by this situation. This disease, which is seen in 10% of adults in the world, is unfortunately more common in our country. For chronic kidney disease, which manifests itself in the last stages that progress silently, it is often late in terms of treatment. Especially those with diabetes, hypertension, obesity, smoking, recurrent urinary tract infections and rheumatological diseases are at high risk. The effect of uremia on the microbiota was investigated. They exhibit a microbiota enriched with Urease and Uricase enzymatic activities has been found and this affects the metabolism of urea. As a result of many studies, it supports a new option for CKD treatment by directing the microbiota.
It is a disease that progresses in the form of memory loss, dementia, and general decline in cognitive functions, which develops due to the death of brain cells over time. People who develop Alzheimer’s have beta amyloid plaques in the brain. This disease, which manifests itself with only minor forgetfulness in the initial phase, may progress in the form of forgetting the events experienced over time, not remembering family members, not being able to do many things physically, and not being able to meet basic needs.
EPILEPSY The brain works by transmitting information between neurons or other receptor or effector cells with electrochemical vibrations. This transmission is accomplished by chemical charges and electrical vibrations. In other words, our brain is an electro-chemical organ and every person has an electrical activity in their brain. In epilepsy, which is a chronic disease, sudden and uncontrolled discharges occur in neurons of the brain. As a result, the patient may experience involuntary contractions, sensory changes and confusion in consciousness.
In 2017, the first case of using FMT after epileptic seizures was reported. (114) In this study, it was found that a girl with a 17-year history of epilepsy provided remission of intestinal and neurological symptoms. After 20 months of follow-up and discontinuation of antiepileptic drugs, it proved its effectiveness in preventing relapse of seizures. AUTISM Autism is a personal disorder that generally starts in 3-year-old children and continues throughout life. It is the state of being unable to establish a proper verbal or non-verbal relationship with one’s surroundings. Today, the diagnosis can be easily made through some tests. Early diagnosis and appropriate rehabilitation program are very important in treatment. Although the exact cause of autism is not known, it is thought to be genetic. A total of 38 studies, 25 animals and 15 humans, were analyzed. According to these analyzes, probiotics; It has shown effectiveness in relieving behavioral styles related to psychiatric disorders such as anxiety, depression, obsessive-compulsive disorder and memory abilities. There are reports of symptom remission in two autistic children after FMT application. It has even been suggested that FMT can improve both gastrointestinal and autism symptoms by increasing bacterial diversity and altering the gut microbiota. It was proven on a mouse that Bifidobacterium fragilis bacterium can improve anxiety-like behavior, sensory transmission, and communicative behavior.
AUTOIMMUNE DISEASES It is a condition in which the immune system mistakenly attacks the body’s normal tissues. The immune system protects the body against germs such as bacteria and viruses. When foreign bacteria and viruses enter the body, it activates the defense cells. In autoimmune diseases, the immune system perceives different parts of the body as a threat and attacks the body. In a study with the use of FMT, it was shown that platelet counts returned to normal. The immune system and the microbiota are a highly interconnected duo. Therefore, it is quite normal for intestinal microbial dysbiosis to play a role in autoimmune disorders. ALLERGIC PROBLEMS All allergies differ from person to person. The severity of the allergy condition has an impact on the symptoms. Runny nose, congestion, frequent sneezing, itching, chronic cough, shortness of breath, wheezing, rash and swelling in the body can be counted among the symptoms. There is strong evidence to suggest that the gut microbiome dysbiosis plays an important role in the etiopathogenesis of these disorders. With FMT application, it is possible to provide immune homoeostasis with stable and colonizing bacteria. HEMATOLOGICAL DISEASES Hematology is a branch of science that deals with the prevention, diagnosis, treatment and follow-up of problems related to blood, lymph nodes, spleen and bone marrow. Congenital problems and subsequent diseases that cause low and high blood levels, blood clots and vascular occlusions, blood and bone marrow cancers, immune system diseases, benign problems that cause lymph node and spleen enlargement, and all cancers are diseases in the field of hematology.
As a result, the gut microbiome was found to have an effect on hematopoiesis. Antibiotics used for a long time deplete the intestinal microbiota and impair hematopoiesis. With FMT it is possible to rebuild this broken system.
TUMOR AND GUT MICROBIA A tumor is a solid mass of tissue formed by abnormally clumping cells. Tumors can affect tissues, skin, bones, organs, and glands throughout the body. Although most tumors are not cancerous, they are benign. However, most tumors still require treatment. In addition, malignant tumors can be life-threatening and require cancer treatment. There are more than one kilogram of microorganisms in the digestive system. All of these are considered to be the most important microorganisms in the human body, and they are all called the gut microbiota. A strong link has been shown between the gut microbiome and cancer. The gut microbiome is one of the important modules of immunity and may influence the outcome of cancer immunotherapy. Therefore, FMT is also used during these weeks. FMT from humans to mice has been shown to promote the growth of a bacterium with anticancer properties by treating patients with melanoma. Oral administration of this bacterium alone can cure it to the same degree as tumor control therapy, and combination therapy can almost completely eliminate tumor growth. The results show that manipulating the gut microbiota can modulate cancer immunotherapy.
Conclusion
FMT has become a well-established procedure and the most effective treatment option for recurrent clostridium difficile infection. Increasing studies alongside the treatment of Clostridium difficile have shown that FMT offers potential and promising clinical indications for the treatment of many other disorders related to gut microbial dysbiosis. In addition, high-quality studies are needed to further determine the efficacy and safety of FMT for both intra-intestinal and extra-intestinal disorders. It is of great value to elucidate the effects of FMT as a promising alternative therapy for the intestinal microbiome and several related diseases.