Fecal Microbiota Transplantation (FMT)

What is the usual compositon of human feces?

A detailed analysis of the usual compositon of human 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.

What is the definition of Fecal Microbiota Transplantation (FMT)?

The definiton of FMT is the transmission of diversity of gut microbiota (bacteria , viruses , fungi , archaea) within a prescreened stool from healthy donors into the gastrointestinal tract of patients. (2, 3, 14).

What role does Fecal Microbiota Transplantation (FMT) play in manipulating the gut microbiota?

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

What are the results of Fecal Microbiota Transplantation (FMT)?

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).

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).

What influence does Fecal Microbiota Transplantation (FMT) have on colonization resistance?

Fecal Microbiota Transplantation (FMT) and standardized stool-based products consistently restore colonization resistance by

• the restoration of secondary bile acids,


• the exclusion of nutrient niches, and


• the suppression of opportunistic pathogens (30).

How Do Donor–Recipient Bacterial Interactions Predict FMT Success?

The relationship between donor bacteria in FMT and clinical success is inconsistent. Tracking bacterial strains is difficult because genetic markers are often missing or cannot be assigned unambiguously (31)

One possible solution is to use so-called Species Genome Bins (SGBs) to track closely related groups of bacteria. Interactions between donor and recipient bacteria helped donor strains become established. These interactions often also involved bacteria that were not closely related. A match between the donor’s and recipient’s SGBs predicted successful bacterial strain transfer (31)

The same patterns appeared in FMT studies involving several other diseases, including autism and gastrointestinal disorders. The findings could explain why FMT works better for some people than for others (31)

How is Fecal Microbiota Transplantation (FMT) conducted?

Fecal Microbiota Transplantation (FMT) is conducted by several delivery methods 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, nasoduodenal tube, 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 (4, 5, 7, 17) aiming to improve the dysbiotic condition by increasing overall diversity and also restoring the functionality of the microbiota (4, 5).

What are the advantages of Fecal Microbiota Transplantation (FMT)?

The advantages of Fecal Microbiota Transplantation (FMT) are:

• Restore healthy microbiome with microbiota from donor


• No risk of antibiotics resistance


• High cure rate, low relapse rate in Clostridioides difficile infection (CDI)


• Under strict regulations due to safety concerns;


• Potential but uncertain therapeutic effects for other disorders (21)

What are the challenges faces Fecal Microbiota Transplantation (FMT)?

Several challenges faces FMT are:

• Donor Selection: Identifying suitable donors is critical to ensure safety and efficacy.


• Risk of Transmission: There is a possibility of transmitting infectious or non-communicable risks through FMT, and an 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, 29)


• Mechanistic Understanding: The mechanisms driving the benefits of FMT are not fully understood (29).

FMT involves problems with reproducibility and scalability, which are compounded by the transmission of gut microbiota diversity (2, 3, 14).

Fecal Microbiota Transplantation (FMT) is often associated with a social stigma due to its nature (23). One of the challenges with FMT is the difficulty in standardizing fecal matter, which raises various ethical and social concerns regarding feces transplants. Additionally, monetizing FMT presents its own set of challenges.

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).

Are there any alternatives to Fecal Microbiota Transplantation (FMT) in sight?

There is a growing interest in finding alternatives to direct FMT (24). One promising alternative is the use of gel capsules containing fecal microbiota. These capsules offer several advantages, such as eliminating the need for invasive gastrointestinal procedures (25, 26]. This method is generally preferred by patients (27, 28).

Private companies have started providing FMT through oral capsules, primarily targeting the treatment of Clostridioides difficile infection (CDI). However, the effectiveness of these capsules compared to traditional FMT remains uncertain.
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).

History of Fecal Microbiota Transplantation (FMT)

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).

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
(23) Anderson et al. 2012 Aliment Pharmacol Ther 36(6): 503-16
(24) Hawkins & O'Doherty 2011 BMC Med Genomics 4: 72
(25) Youngster et al. 2014 Clin Infect Dis 58(11): 1515-22
(26) Youngster et al. 2014a JAMA 312(17): 1772-8
(27) Zipursky et al. 2012 Clin Infect Dis 55(12): 1652-8
(28) Brandt et al. 2012 Am J Gastroenterol. 107(7): 1079-87
(29) Sen et al. 2026 Cell Host Microbe 34(7): 1202-1219
(30) Engevik et al. 2026 Cell & Host Microbe 34(7): 1220-1240
(31) Chen et al. 2024a Cell Host & Microbe 32(3): 349-365

see also:
Adverse Events / Safety & Fecal Microbiota Transplantation (FMT)
Application & Fecal Microbiota Transplantation (FMT)
Dysbiosis & Restoration
Fecal Microbiota Transplantation (FMT) & Clostridioides difficile infection (CDI) (recurrent)
Fecal Microbiota Transplantation (FMT) (non-standardized) & Preclinical/Clinical data & Combinations
Fecal Microbiota Transplantation (FMT) (non-standardized) & Preclinical/Clinical Data & Monotherapy
Approvals / Regulatory affairs & Fecal Microbiota Transplantation (FMT)
Adverse Events / Safety & Fecal Microbiota Transplantation (FMT)
MaaT011
MaaT013
MaaT033
Microbial Ecosystem Therapeutics (MET)
PRIM-DJ2727
Probiotics (living agents)
VE303