Fecal Microbiota Transplantation (FMT)

Fecal microbiota transplantation (FMT) is currently the most effective Manipulation / Modulation of Gut microbiota (1)

It is the transmission of diversity of gut microbiota (bacteria , viruses , fungi , archaea). However, it involves problems with reproducibility and scalability, which are compounded by the transmission of gut microbiota diversity (2, 3, 14).

A detailed analysis of feces from adults on a typical British diet found an average daily fecal discharge of 100 g, with only 25% as dry mass (22). The dry mass was 55% microorganisms, with the rest mostly fibers like cellulose, and soluble components (24%) such as mucus, colonocytes, proteins, fat, and small molecules like bile acids.

Fecal Microbiota Transplantation (FMT) is the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients. The delivery method will differ based on clinical context. Each method has advantages and disadvantages that should be considered on a case-by-case basis. The delivery methods include upper endoscopy, nasoenteric tubes, or capsules (e.g., with frozen or lyophilized content) for upper gastrointestinal tract transplant delivery, and colonoscopy, flexible sigmoidoscopy, or enema for lower gastrointestinal tract transplant delivery. It is gaining increasing importance in both the clinical and research settings. Numerous clinical trials have been undertaken, using Fecal Microbiota Transplantation (FMT) and other gut microbiota modulation strategies to treat diseases of the gut (such as CDI, and inflammatory bowel disease,) as well as other systemic diseases - including metabolic syndrome, autism, multiple sclerosis, Parkinson’s disease, and even cancer (7, 17).

Fecal microbial transplantation can be delivered to the lower gastrointestinal tract via colonoscopy or enema or the upper gastrointestinal tract via nasoduodenal tube or capsules to improve the dysbiotic condition by increasing overall diversity and also restoring the functionality of the microbiota (4, 5).

Fecal Microbiota Transplantation (FMT) does not selectively target intestinal bacteria, but it likely affects and is affected by the various members of the gut microbiota (6). After FMT the recipient microbiota was characterized by increased diversity, increased abundance of various Firmicutes and Bacteroidetes, and decreased abundance of Proteobacteria (16).

There is an interest in extending Fecal Microbiota Transplantation (FMT) to other diseases affecting the gastrointestinal tract, such as inflammatory bowel disease (IBD ), graft versus host disease (GVHD), metabolic syndrome, and immune checkpoint inhibitor-associated colitis (ICIAC) (7, 8, 9, 10, 11, 12).

Guidelines for proper treatment and screening of donor stool are critical for safety. They include screening for infectious diseases and disorders that are associated with perturbations of the gut microbiota, as well as the use of medications that can affect gut microbes, such as antibiotics and proton pump inhibitors (13).

Bacterial strains transferred in Fecal Microbiota Transplantations (FMTs) have been shown to persist in the recipient colon for at least three months, raising the possibility of long-term health benefits (15).

Fecal Microbiota Transplantation (FMT) was abandoned for many years until its resurgence for treatment of Clostridioides (formerly Clostridium) difficile infection (CDI), first reported by Schwan et al. in 1983 (18).

In the 1950s, groundbreaking studies showed that fecal matter from a healthy person could be transferred to patients who had experienced microbiome depletion due to antibiotics, providing them with resistance to bacterial pathogens (19, 20). Eiseman and colleagues described four patients with Staphylococcal pseudomembranous enterocolitis who improved after fecal enemas (20).

Advantages and disadvantages of Fecal Microbiota Transplantation (FMT) are:

• Restore healthy microbiome with microbiota from donor;


• No risk of antibiotics resistance;


• High cure rate, low relapse rate;


• Under strict regulations due to safety concerns;


• Potential but uncertain therapeutic effects for other disorders
  But:


• uncertainty of transmitting undetected pathogens and other undefined microbes associated with them development of various disorders including obesity, metabolic syndrome, other signs of abdominal discomfort and autoimmune diseases (21)

References:

(1) Vendrik et al. 2020
(2) Zuo et al. 2018 Nat. Commun. 9: 3663
(3) Wargo 2020
(4) Allegretti et al. 2018 Gastrointest Endosc 87: 18–29
(5) Chande et al. 2020 Inflamm Bowel Dis 26: 843-851
(6) Leonardi et al. 2020 Cell Host & Microbe 27: 823-829
(7) Allegretti et al. 2019 Lancet 394: 420-31
(8) Vrieze et al. 2012 Gastroenterology 143(4): 913-17
(9) Kakihana et al. 2016 Blood 128(16): 2083-2088
(10) Paramsothy et al. 2017 The Lancet 389: 1218-1228
(11) Weingarden & Vaughn 2017 Gut Microbes 8: 238–252
(12) Wang et al. 2018d Nat Med. 24: 1804–1808
(13) Cammarota et al. 2019 Gut 68: 2111
(14) DeFilipp et al. 2018 Blood Advances 2: 745
(15) Li et al. 2016b Science 352: 586–589
(16) Seekatz et al. 2014 mBio 5(3): e00893-14
(17) Zhang et al. 2012a The American Journal of Gastroenterology 107(11): 1755
(18) Schwan et al. 1983 Lancet 2(8354): 845
(19) Bohnhoff et al. 1954 Proc. Soc. Exp. Biol. Med. 86: 132
(20) Eiseman et al. 1958 Surgery 44(5): 854-9
(21) Wang et al. 2016a PLoS One 11: e0161174
(22) Stephen & Cummings 1980 J Med Microbiol 13: 45-56

see also:
Application & Fecal Microbiota Transplantation (FMT)
Dysbiosis & Restoration
Fecal Microbiota Transplantation (FMT) & Preclinical/Clinical data & Combinations
Fecal Microbiota Transplantation (FMT) & Preclinical/Clinical Data & Monotherapy
Fecal Microbiota Transplantation (FMT) & Regulations
Adverse Events / Safety & Fecal Microbiota Transplantation (FMT)
MaaT011
MaaT013
MaaT033
Microbial Ecosystem Therapeutics (MET)
PRIM-DJ2727
Probiotics (living agents)
VE303