Introduction


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Introduction


Jessica R. Allegretti, MD, MPH and Zain Kassam, MD, MPH


Mrs. Smith is an 82-year-old British woman who loosely resembles the Queen. She loves rose gardening and her grandchildren more than anything else in the world. Today, she is teary-eyed in clinic having suffered with Clostridioides difficile infection (CDI) for longer than she can remember. Most recently, she’s been tied to the toilet for the past week and nearly fell rushing to the bathroom for her ninth watery bowel movement of the day. Five courses of antibiotics have failed to cure her CDI, and the symptoms seem to come back each time with more vengeance. Her grandson sent her an article on fecal transplants, and she wonders if this might be right for her.


Clinically, this scenario is strikingly common. The exponential rise of scientific literature and wide popular media coverage of both the microbiome and fecal microbiota transplantation (FMT) have ushered in the potential of the microbiome revolution in medicine. The elegant hypothesis that a patient’s disease is a result of an abnormal microbiome, or dysbiosis, and if one restores the microbiome to homeostasis by FMT from a healthy donor it may treat, or even cure, a disease has captured the imagination of scientists, clinicians, and patients.


FMT is the first success story of a broader class of exciting microbiome therapeutics. A systematic review and meta-analysis of randomized clinical trials for FMT in recurrent C. difficile infection (rCDI) has reported a number needed to treat (NNT) of 3,1 meaning a clinician needs to treat 3 rCDI patients with FMT to prevent rCDI in a single patient. By comparison, the NNT for aspirin following ST-elevation myocardial infarction to prevent a single death is 42.2 Despite a lack of large, well-designed, placebo-controlled trials, the striking effect size for FMT and paucity of effective treatments for rCDI have led to its recommendation in both US and European CDI clinical practice guidelines.3,4 Although data on FMT and microbiome therapeutics are continuing to emerge, this novel therapeutic is here to stay.


That said, the name fecal microbiota transplantation may not be here to stay. Many feel the term is not medically accurate, because the intervention transfers intestinal microbiota that engraft into a recipient, as opposed to transplanting feces, or stool, a complex substrate.5 Additionally, the term may not be patient-centric and may dissuade patients who perceive FMT as the direct transfer of whole feces. Accordingly, the term intestinal microbiota transplantation and variations such as intestinal microbiota transfer or intestinal microbiome therapy have been proposed. As with many novel therapies, medical nomenclature changes; however, for the purpose of this book, we will continue to refer to the intervention as fecal microbiota transplantation or FMT.


Despite an evolving nomenclature, there is a major need for clinician-orientated education about FMT given the field is in its infancy. Practical FMT workshops or a dedicated clinical FMT fellowship is needed; however, currently these do not exist. So, how do medical trainees, practicing physicians, nurses, and allied health care members learn about the real-world aspects of FMT? That is the purpose of this book, The 6 Ds of Fecal Microbiota Transplantation: A Primer From Decision to Discharge and Beyond. This book aims to provide you with the practical tools and a simple clinical framework to understand FMT and administer end-to-end comprehensive FMT care. This book emphasizes practical pearls and checklists developed by leading world experts who have collectively cared for thousands of patients suffering from rCDI who have ultimately benefited from FMT. Given the popular media attention, patients often have questions about this novel therapy, and this book has practical responses to the most frequently asked questions.


Given the field of the microbiome is relatively new to clinicians, in Chapter 2, we review the nuts and bolts of the microbiome. What is it? How do you assess the microbiome? Why does it matter? Building on the new field of the microbiome, in Chapter 3 we revisit the history of the FMT, because to move forward, we must understand the past. When was FMT first described? How has it evolved?


From there, we introduce a simple practical framework for FMT: the 6 Ds.



  1. Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?
  2. Donor: How do you select a donor for FMT? How do you screen a donor?
  3. Discussion: Navigating the risks, benefits, and alternatives in the informed consent process for FMT. What are the short-term risks? What are the long-term risks?
  4. Delivery: What is the best delivery method for FMT? Should I use a colonoscopy, enema, or capsules?
  5. Discharge: What is the ideal post-FMT care? How should I counsel my patients following FMT?

This pragmatic framework will provide clinicians with the real-world knowledge to administer FMT and navigate nuanced clinical cases of rCDI.


6. Discovery: We move beyond CDI and highlight the most promising clinical conditions in which FMT has been explored, from other gastrointestinal diseases, like irritable bowel syndrome and inflammatory bowel disease, to infectious conditions, such as enteric antibiotic-resistant bacteria, to liver and metabolic diseases and even neurological conditions. Overall, ongoing basic science and translational and clinical research are promising, and the search for the next condition to respond to microbiome therapies is underway.


As you navigate this book, you will learn the tips and tricks needed to counsel and manage patients like Mrs. Smith. And with time and care, you can provide her with the treatment she needs to break the cycle of CDI and return to her life as a rose gardener and grandmother.


References


1.      Moayyedi P, Yuan Y, Baharith H, Ford AC. Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials. Med J Aust. 2017;207(4):166-172.


2.      Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349-360.


3.      McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48.


4.      Debast SB, Bauer MP, Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(suppl 2):1-26.


5.      Khoruts A, Brandt LJ. Fecal microbiota transplant: a rose by any other name. Am J Gastroenterol. 2019;114(7):1176.


Abbreviations




















































































































































































AGA American Gastroenterological Association
ARB antibiotic-resistant bacteria
ASD autism spectrum disorder
BMI body mass index
BSS Bristol stool score
CD Crohn’s disease
CDC Centers for Disease Control and Prevention
CDI Clostridioides difficile infection
CMV cytomegalovirus
COVID-19 coronavirus disease 2019
CRE carbapenem-resistant Enterobacteriaceae
DIY do-it-yourself
EBV Epstein-Barr virus
EMA European Medicines Agency
EPEC enteropathogenic Escherichia coli
ESBL extended-spectrum beta-lactamase
FAQs frequently asked questions
FDA US Food and Drug Administration
FMT fecal microbiota transplantation
GDH glutamate dehydrogenase
GI gastrointestinal
GMP Good Manufacturing Practice
GvHD graft vs host disease
IBD inflammatory bowel disease
IBS irritable bowel syndrome
IBS-C constipation-predominant irritable bowel syndrome
IBS-D diarrhea-predominant irritable bowel syndrome
IBS-M mixed irritable bowel syndrome
ICI immune checkpoint inhibitor
ICU intensive care unit
IDSA Infectious Diseases Society of America
IgG immunoglobulin G
IND Investigational New Drug
IPAA ileal pouch–anal anastomosis
MRSA methicillin-resistant Staphylococcus aureus
NAFLD nonalcoholic fatty liver disease
NASH nonalcoholic steatohepatitis
NGT nasogastric tube
NNT number needed to treat
OHE overt hepatic encephalopathy
OR odds ratio
PCR polymerase chain reaction
PD pharmacodynamic
PDAI Pouchitis Disease Activity Index
PK pharmacokinetic
PSC primary sclerosing cholangitis
rCDI recurrent Clostridioides difficile infection
rRNA ribosomal RNA
RYGB Roux-en-Y gastric bypass
SARSCoV-2 severe acute respiratory syndrome coronavirus 2
SCFA short-chain fatty acid
SIBO small intestinal bacterial overgrowth
SOC standard-of-care
SOT solid organ transplant
STEC Shiga toxin–producing Escherichia coli
toxin EIA toxin enzyme immunoassay
UC ulcerative colitis
UTI urinary tract infection
VRE vancomycin-resistant Enterococcus

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May 23, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on Introduction
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