Trends in Microbiology
OpinionSpecial Issue: Infection Biology in the Age of the MicrobiomeImproving Risk–Benefit in Faecal Transplantation through Microbiome Screening
Section snippets
The Clinical Potential of FMT
FMT has emerged as a transformative treatment for recurrent Clostridioides difficile infection (CDI) [1], providing outcomes that are substantially better that those associated with standard antibiotic therapy [2,3]. FMT involves the instillation of a preparation of donor stool into the intestinal tract of a patient, and has also shown promise in the treatment of noninfectious inflammatory bowel disorders and nonenteric conditions, particularly those relating to metabolic disease and
Safety Concerns
The increasingly widespread and often poorly regulated use of FMT has raised concerns about potential infection risks. Introducing a microbiologically complex material into a recipient is inherently hazardous, and the FDA recently reiterated its warning to patients that the procedure should be used only as a last resort [5]. A recent review of FMT safety found that serious adverse events occur in 2–6% of patients, depending on the route of administration [6]. The incidence of severe infections
The Influence of the Gut Microbiota on Infection
There are multiple complementary mechanisms by which commensal microbiota are able to prevent pathogen proliferation and infection. The majority of patients who receive FMT, such as those with C. difficile colitis, have substantial pre-existing depletion of commensal populations [13]. This disruption of the normal intestinal microbiota increases susceptibility to pathogen colonisation and is likely to explain the increased risk of subsequent sepsis in this population [14]. The relative ability
Approaches for Selecting or Improving Donor Microbiota Composition
Reduced faecal bacterial diversity is also associated with an increased risk of pathogen colonisation and systemic infection [17], suggesting this factor should be considered when assessing donor material. However, bacterial diversity is likely to be less important as an indicator of beneficial microbiota in its own right than as an indicator of the probability that the transplanted material contains specific microbial traits. In particular, the presence of beneficial keystone taxa can have a
FMT Processing to Preserve Microbiota Composition and Function
FMT material usually undergoes multiple processing steps, such as blending, filtering, and freezing, often performed under aerobic conditions. The processing methods used are highly variable and centre-specific.
The effects of processing on the viable microbiota composition of instilled material are not typically considered. However, certain processing steps, particularly blending in aerobic conditions, result in profound changes in the final viable microbiota composition that are not dissimilar
Modifying Donor Microbiota to Reduce Sepsis Risk
Stringent screening already makes the recruitment of suitable donors for FMT a major challenge. The exclusion of donors with an undesirable microbiota composition could result in a substantial further reduction in the donor pool. However, although inappropriate processing practices can modify the composition of the viable stool microbiota in a detrimental manner, modification of donated stool to improve its microbiological characteristics might allow material to be used from a wider donor
Overlap between Safety and Benefit
To date, interest in the microbiome traits of donor faeces has focused on improving treatment efficacy rather than safety [39]. However, there can be considerable overlap in achieving these separate goals. The same bacterial profiles that protect against infection and chronic disease (Box 4) also appear to be associated with clinical benefit following FMT. For example, donor-specific differences in clinical outcomes, also referred to as the super-donor effect, have been observed in the context
Can FMT Be Used to Prevent Pathogen Colonisation and Infection?
We began by discussing the transmission of drug-resistant bacterial pathogens through FMT. We will conclude by looking at the evidence that FMT can be used to achieve the opposite outcome: clearance of intestinal colonisation of drug-resistant pathogens, and reduced infection. First, FMT is capable of rapidly clearing colonisation by both VRE and carbapenem-resistant bacteria in murine models [47]. Several case studies have also temporally associated pathogen clearance with FMT [48,49]. In C.
Concluding Remarks
Efforts to improve the safety of FMT are essential but should not inadvertently undermine access to life-saving FMT for the treatment of CDI or discourage the investigation of FMT in clinical trials that could deliver important new therapeutic options for a range of diseases. Although current screening processes have an excellent track record of safety, much is still not known about how donor microbiota influence infection risk or which microbiome parameters should be used to screen donors (see
Glossary
- Allogeneic stem-cell transplantation
- transplantation from another person of cells with the ability to regenerate multiple types of new cells. This procedure is commonly used as part of the treatment of leukaemia and other blood cancers.
- Bacterial diversity
- the number, distribution, phylogenetic relatedness, and functional characteristics of the bacterial taxa associated with a given niche.
- Bacteriocins
- proteinaceous compounds produced by one type of bacteria that inhibit or kill other bacteria.
References (73)
The evolution of the use of faecal microbiota transplantation and emerging therapeutic indications
Lancet
(2019)Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn's disease and recurrent Clostridium difficile infection
J. Crohns Colitis
(2014)From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites
Cell
(2016)Depletion of butyrate-producing clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella
Cell Host Microbe
(2016)Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae
Cell Host Microbe
(2007)Bacterial viability in faecal transplants: which bacteria survive?
EBioMedicine
(2019)Cooperating commensals restore colonization resistance to vancomycin-resistant Enterococcus faecium
Cell Host Microbe
(2017)A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility
Cell
(2016)Donor feces infusion for eradication of extended spectrum beta-lactamase producing Escherichia coli in a patient with end stage renal disease
Clin. Microbiol. Infect.
(2014)A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial
Clin. Microbiol. Infect.
(2019)
Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them
Mucosal Immunol.
Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection
Aliment. Pharmacol. Ther.
Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection
Aliment. Pharmacol. Ther.
Fecal microbiota transplantation is superior to fidaxomicin for treatment of recurrent Clostridium difficile infection
Gastroenterology
Important safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse reactions due to transmission of multi-drug resistant organisms, FDA
Systematic review: adverse events of fecal microbiota transplantation
PLoS One
Multi-organism bacteremia after fecal microbiota transplantation for relapsing Clostridium difficile infection
Am. J. Gastroenterol.
European consensus conference on faecal microbiota transplantation in clinical practice
Gut
Challenges in fecal donor selection and screening for fecal microbiota transplantation: a review
Gut Microbes
Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant
N. Engl. J. Med.
Adapting Koch's postulates
Science
Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection
Microbiome
Hospitalization type and subsequent severe sepsis
Am. J. Respir. Crit. Care Med.
Microbiota-mediated colonization resistance against intestinal pathogens
Nat. Rev. Immunol.
Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation
Clin. Infect. Dis.
Keystone taxa as drivers of microbiome structure and functioning
Nat. Rev. Microbiol.
Formation of propionate and butyrate by the human colonic microbiota
Environ. Microbiol.
The evolution of cooperation within the gut microbiota
Nature
Structure, function and diversity of the healthy human microbiome
Nature
Colonization resistance
Antimicrob. Agents Chemother.
The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection
Microbiol. Spectr.
Gut inflammation provides a respiratory electron acceptor for Salmonella
Nature
Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans
J. Clin. Invest.
The microbiome and metabolome of preterm infant stool are personalized and not driven by health outcomes, including necrotizing enterocolitis and late-onset sepsis
mSphere
Microbiota-activated PPAR-gamma signaling inhibits dysbiotic Enterobacteriaceae expansion
Science
Donor recruitment for fecal microbiota transplantation
Inflamm. Bowel Dis.
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2022, Cancer LettersCitation Excerpt :However, it is heartening to note that two clinical trials (NCT04729322/NCT04130763) have been approved to explore the use of FMT for improving the efficacy of anti-PD-1. The unidentified composition and pathogenicity of fecal bacteria have made the safety and efficacy of FMT in cancer treatment the core study in this promising field [97]. The most desirable final state for FMT as a therapy for various human diseases is the precise and personalized regulation of the intervention to gut microbiota.
Resveratrol and its derivates improve inflammatory bowel disease by targeting gut microbiota and inflammatory signaling pathways
2022, Food Science and Human WellnessCitation Excerpt :But it is difficult to develop accurate personalized medical strategies [97]. Also, FMT is associated with greater risk and and it is difficult to determine the source of risk [98]. In contrast, resveratrol, as a Chinese herbal medicine ingredient, has a relatively wide range of sources and has less toxic and side effects than FMT, it may provide the best raw materials for beneficial symbiotic (or transplanted) microbes (such as Lactobacilli, Bifidobacteria), which can have a significant effect on gut microbiota composition in the short term.
Power calculations for detecting differences in efficacy of fecal microbiota donors
2020, Contemporary Clinical Trials CommunicationsCitation Excerpt :However, given the enormous complexity of stool –which includes bacteria, viruses, fungi, microbe-derived molecules, and host-derived molecules– and the variability of stool from person to person [5,6], it stands to reason that different stool could have different ability to treat disease. Anecdotes from FMT research, particularly in ulcerative colitis [7,8], have created interest in the possibility of “donor effects”, that is, in potential variability in the efficacy of different donors’ stool [9–12]. A “donor effect” refers to the possibility that stool from some donors is more efficacious than stool from other donors for treating some indication.
Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy
2020, Pharmacology and TherapeuticsCitation Excerpt :Fecal microbiota transplantation was demonstrated to be effective in several clinical approaches (Papanicolas & Gordon, 2020). Yet, the risks of stool transplantation must be taken into consideration as well as the transmission of antibiotic-resistant pathogens (Papanicolas & Gordon, 2020). Beside a vegan diet, reducing the total amount of fat intake is advisable to prevent CVD.
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