Fecal Transplant.
The fight against frequent and inappropriate use of antibiotics, and gastrointestinal diseases. The future of bacteriotherapy.
Bacteriotherapy has grown increasingly popular given its success against several gastrointestinal diseases. Forms of bacteriotherapy include the use of probiotics, and/or microorganisms. Fecal transplantation is a form of bacteriotherapy; a new solution designed for treating cumulating bacteria and recurrent C. difficile. FMT is the transfer of stool samples — colonoscopy or capsule — from a healthy donor directly into the gastrointestinal tract of a recipient with microbial imbalance. This diversifies the number of bacteria; changes the patient’s microbial structure and has proven to be effective in relieving gastrointestinal infections and resolving dysbiosis of the gut microbiome. Fecal transplants may sound preposterous, however, it is the solution to the ever-growing problem of C. difficile. The negative stigma circulating this new medical advancement leaves patients hesitant and only receptive as a last resort. However, in past speculations, FMT will be used more commonly in the medical field to treat a myriad of gastrointestinal problems.
The left illustration exhibits the intestinal immune system at homeostasis. Here, the gut microbiome remains tolerant in the gut lamina and stimulates the proper antimicroboal response in the intestinal lumen. At symbiosis, the intestinal lumen possesses stable abundance and diversity.
The right illustration exhibits the intestinal immune at dysbiosis. Here, the gut microbiome presents a dysregulated immune response. At dysbiosis, as the microbial diversity and short-chain fatty acids decrease, the microbial instability is inversely proportional (biomedcentral.com 2021).
Throughout various cultures, humans have consistently consumed fermented foods for centuries. Though fermented foods were originally devised to manipulate food cells, essentially allowing them to retain their vitality, the current consumption and production of fermented foods are high in demand due to their many health benefits. Fermented foods are rich in beneficial bacteria known as ‘probiotics’ and thus, have gained enormous popularity.
During the early studies of Elie Metchnikoff, a Russian immunologist, and microbiologist, he observed the lifespan of Bulgarians in the 1900s; his research concluded that approximately four out of every thousand Bulgarians lived to be past 100 years of age (Kerry 2012). From this study, Metchnikoff believed that auto-intoxication led to the degenerative processes associated with aging (Gordan 2016) and established a correlation between Bulgarians’ exceptionally long lifespans to their regular consumption of fermented milk.
‘Yogurt,’ was discovered to contain host-friendly bacteria, “Bulgarian Bacillus.” Which manipulates the intestinal microsomes of the gut — promoting health and longevity. This raises the question, “what is the need for fecal transplant with the existence of fermented foods?”
Need for Fecal Transplants . . .
Later called ‘Lactobacillus bulgaricus,’ was found to not be able to survive in the human gut (Kerry 2021).
The symbiotic relationship between gut flora and humans’ digestive system was found weakened, since the invention of antibiotics. Antibiotics were discovered to have a major impact on the host’s immunity through the alteration of bacterial metabolites and along with the signals transmitted from gut microbiota through the host (Zhang et. al. 2019).
Through further metabonomic analysis, it has been revealed that antibiotics have a negative and profound effect on “lipids, bile acids, amino acids, and amino acid-related substances in the gut.” But the restoration of bile acid to mediate the resistance against Clostridium difficile still remains. This is significant because C. difficile is a major illness that typically occurs after the use of antibiotic medications and fecal transplants are recommended for patients whose C. difficile.
Though fecal transplants are a relatively new procedure within the medical field, it is highly recommended in fighting against c. difficile — for fecal transplantation yields high efficacy for the treatment of C. difficile infection by an overall cure rate of 91–93% (Brandt, 2012).
Fecal transplants treat stomach infections by the transfer of a stool sample from a healthy individual to the recipient with microbial imbalance; by introducing healthy bacteria and diversifying the bacterial species from the stool sample, a positive change in the microbial composition of the colon will prevent C. difficile from cultivating.
An individual is exhibited to be experiencing the symptoms of clostridium difficile colitis: diarrhea, belly pain, and a fever.
The bottom right-hand side of the image displays an illustrated representation of c. difficile infection; inflammation of the inner linings of his colon possibly due to a decrease in microbial diversity. The upper right-hand side of the image displays a healthy colon, not suffering from c. difficile possibly due to a more diverse microbiota colon (mayoclinic.org 2019).
Clostridium difficile . . .
Clostridium difficile is a common bacterial infection that causes severe diarrhea and colitis, by the emission of harmful toxins to the colon. These toxins are the root of these gastrointestinal problems and inflammation of the colon — known as colitis. C. difficile develops in two forms: bacteria and spores. Unlike bacteria, spores are described as inactive and noninfectious, which means that they can survive in the host immunity’s environment for a long period, and enter the active state when the host is on antibiotics (medicinenet.com, 2020).
C. difficile is often acquired after antibiotic complications. Antibiotics — commonly prescribed: penicillin, amoxicillin, and cephalosporins — are suspected of killing the healthy protective bacteria — “friendly flora” — in the bowel that prevent the rapid growth of C. diff.
Thus, symptoms of diarrhea after taking antibiotics is fairly common (cdc.gov, 2021). Other symptoms of C. diff include: abdominal cramping and a fever.
Other risk factors of C. difficile include aging — being 65 or older — and individuals with a developing or genetically weak immune system.
Aside from the genetic factors or use of antibiotics being the cause of a weak immune system; individuals with illnesses such as HIV/AIDS and cancer, or patients with an organ transplant and taking immunosuppressive drugs are also susceptible to developing a weak immune system (cdc.gov, 2021). Since C. diff is a recurrent infection — with 25% of patients recurring, regardless of treatment (Terrier et al, 2014) — previous infection with C. diff and/or known exposure to the germs — from a recent hospital or nursing home stay — is an accommodating risk. In addition, the center for disease control estimated C. difficile to be the cause of approximately 500,000 reported infections in the United States each year.
Method of Fecal Transplant . . .
Two possible methods for administering decal transplants are: fecal capsules and colonoscopy. Before proceeding with a method, healthy candidates are screened by a physician for fecal matter transplant donor eligibility. Donor eligibility requires clearances of any gastrointestinal problems. Exclusion criteria would be any history of infections, constipation, chronic use of laxatives, and use of medications (antibiotics especially) in the prior three months (Allegretti et. al, 2014).
A method of transplanting fecal material into the colon of a patient suffering from c. diff. Fecal matter taken from a healthy donor is dried, frozen, and then stored into a capsule for administration.
To perform a colonoscopy, the patient is given diet restrictions and an oral vancomycin prescription. In addition, pre-colonoscopy bowel preparation is performed in advance. Gastroenterologist first examines the mucosal walls of the terminal ileum for evidence of a degree of inflammation that is deemed safe to continue the procedure. After a healthy donor is identified patients are instructed to stop any antibiotics, at least 48–72 hours prior to the procedure (retroflexion.com, 2015).
On the day of fecal matter transplant by colonoscopy, a colonoscope is inserted into the colon: terminal ileum, where the healthy donor stool is directly deposited. For fecal matter transplant by capsule, after a healthy donor is identified, their fecal material is dried, frozen, and then stored in a three-layer gelatin capsule. Fecal capsules are prescribed orally but are reported to have no taste. The duration of treatment and frequency vary patient-to-patient.
Part A: displays the appendiceal orifice; a crescent shape, formed by the superior and inferior lips of the ileocecal valve leading to the terminal ileum.
Part B and C: displays the fecal transplant extract orchestrated directly into the cecum through a scope. Part D exhibits the final procedure; the fecal material is transplanted in the cecum. (retroflexion.com, 2015)
Risks and Benefits of Fecal Transplants . . .
Fecal transplants are beneficial in treating stomach infections. Researchers have claimed a correlation between the lack of microbial—healthy bacteria — diversity to gastrointestinal problems. Thus, the transfer of a stool sample from a healthy donor to the recipient with microbial imbalance. This fecal microbiota introduces healthy bacteria and diversifies the bacterial species. This positive change in the microbial composition of the colon will prevent C. difficile. from cultivating and has yielded high efficacy for the treatment of C. difficile infection with a primary cure rate of 91%, a secondary cure rate of 98%, and an overall cure rate of 91–93% (Brandt, 2012). Risks that patients should consider and speak about with their health care provider before the operation are the fatalities and recurrence rates.
Despite the high success rates, some patients will need more than one FMT treatment and the recurrence rate has been reported to be between 15–35% (Brandt, 2021). Error during the screening of a donor and the possible infections that may follow the procedure may be fatal. The FDA has released a guidance statement of procedure and has released warnings to physicians of a case of two patients who developed conditions worse than the intended infection that the operation meant to cure — C. difficile.
The donor was found associated with STEC infections and the receipt had ultimately died following (fda.gov, 2021).
However, fecal transplants are new to the medical field and many guidelines have been set in place to lower these risks. Understanding the background and regular pre-procedure protocols: sanitation and protective equipment, before a colonoscopy is performed it is important to understand the risks and benefits of fecal transplants. Some guidelines in place today require saline to be used to flush syringes in between infusions.
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