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PROJECT TOPIC AND MATERIAL ON STRAIN TRACKING REVEALS THE DETERMINANTS OF BACTERIAL ENGRAFTMENT IN THE HUMAN GUT FOLLOWING FECAL MICROBIOTA TRANSPLANTATION
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- Name: Strain Tracking Reveals The Determinants Of Bacterial Engraftment In The Human Gut Following Fecal Microbiota Transplantation
- Type: PDF and MS Word (DOC)
- Size: [70 KB]
- Length:  Pages
Fecal microbiota transplantation (FMT) is an emerging treatment for infectious and autoimmune diseases, whereby donor feces are implanted in a patient’s intestinal tract. This treatment cures recurrent Clostridium difficile infection (rCDI) in 85% of cases (van Nood et al., 2013) and there is some evidence it may be effective for other diseases, including inflammatory bowel disease (Moayyedi et al., 2015, Suskind et al., 2015), metabolic syndrome (Ridaura et al., 2013, Vrieze et al., 2012), and autism (Hsiao et al., 2013). Putative mechanisms of FMT efficacy focus on the trillions of bacteria that inhabit the gastrointestinal tract, the gut microbiota. FMT is thought to restore these bacteria (Shahinas et al., 2012, Youngster et al., 2014), which may then alter host metabolism (Floch, 2015, Trompette et al., 2014), inhibit pathogens (Britton and Young, 2014), and effect changes in host immunity (Furusawa et al., 2013, Ivanov et al., 2009, Round and Mazmanian, 2010).
Precision engineering of the gut microbiota with bacterial isolates in pure culture offers the therapeutic potential of FMT without the risks associated with the use of raw fecal matter (Petrof and Khoruts, 2014). Whether this next generation of microbiome-based therapeutics will effectively replace FMT will depend on (1) whether the “active ingredients” of FMT that carry out a desired mechanism can be identified, (2) whether these strains engraft in a patient’s gut, and (3) whether they are sufficiently abundant to produce a clinical response.
While the mechanism may be studied using in vitro or animal models of disease (as for traditional small-molecule drugs), engraftment and abundance in humans are less well understood. If engraftment is governed by simple rules, such as the law of mass action, it may be highly deterministic and easy to predict. Alternatively, if engraftment is governed by contextual factors, such as genetics, diet, antibiotics, and the immune system, it may vary considerably among patients and be difficult to predict. A quantitative model of bacterial engraftment would accelerate drug discovery efforts by pinpointing the bacteria that engraft at high abundance in a given host. However, no such model exists, and despite significant advances in our understanding of FMT (Li et al., 2016), surprisingly few principles of bacterial engraftment in a human host are known.