Nwachukwu Oluomachi prisca seminar slide (6).pptx

Nwachukwu Oluomachi prisca seminar slide (6).pptx

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  FECAL MICROBIOTA TRANSPLANT PAST, PRESENTAND FUTURE NWACHUKWU OLUOMACHI PRISCA 20202230015 FEDERAL UNIVERSITY OF TECHNOLOGY OWERRI IMO STATE. BIOTECHNOLOGY
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  PRESENTATION OUTLINE 1. Introduction 2.History and Timeline of FMT 3. Gut Microbiota 4. Indications of FMT 5. Clostridium 6. Procedure of Fmt 7. Regulatory issues 8. Future directions/research 9. Conclusion
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  Fecal microbiota transplantation(FMT) : It is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s microbial composition and confer a health benefit. (Bakken et al.2011.;Smits et al.2013) INTRODUCTION Fig.1. Fecal Microbiota Transplant
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  HISTORY OF FMT •Ge Hong recoreded the first FMT treatment in the 4th century of the donjin dynasty in China where yellow soup was applied in cases of food poisoning and diarrhea (Zhang et al.2012). • 16th century by Li Shizhen described use of variety of stool products for treatment of diarrhea, fever,pain,vomiting and constipation • 17th century FMT was used in veterinary medicine and later termed “Transfaunation “ • Bedouin groups consumed of their camels poop to take care of their bacterial dysentery. Fig.2. History of FMT
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  FMT IN MODERNSCIENCE (1950 – 2000) Antibiotics, since their discovery generously prescribed, have ended an era in which infectious diseases were the most common cause of death. But antibiotics also came with side effects and antimicrobial resistance in an attempt to ameliorate collateral damage on commensal microbes, bacteriologist Stanley Falkow sampled fecal material from surgical patients before starting them on pre-procedural antibiotics After converting the stools into pill form he prescribed their daily intake to half of the group during post-surgical recovery, an idea so repelling at the time it got him fired when the administrative board found out. In 1958 Dr Eiseman treated four critically ill patients of PMC (Pseudomembranous colitis)with fecal enemas with complete recovery in all the patients
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  Fig.3. FMT INMODERN SCIENCE Fan et al. 2012
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  GUT MICROBIOTA • Theterm ‘microbiota ‘refers to the bacteria,archaea, microeukaryotes and viruses that share the human body space and the may function in a commensal, symbiotic or pathogenic relationship (Hollister et al.2014.) • The term ‘microbiome’refers to the collective genomes of those microorganisms • The human microbiota is estimated to contain 10-100 trillion microbial cells and the intestinal microbiota account for the largest and most diverse population (Qin et al.2010) • It has been estimated that the gut contains 1100 prevalent species and atleast 160 species per individual (Qin et al.2010.) • The human microbiome project revealed variation in the composition of the human gut microbiota between sex,race/Ethnicity and age (Hollister et al.2014.)
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  • Diet isalso related to gut microbiota composition (David et al. 2014) • The microbiota also varies in the composition depending on the location along the Gastrointestinal tract (Eckburg et al.2005;Nava et al.2011) • Metagenomic studies have indicated that the richness gut may be an indicator of health. (Gill et al.2006;Wang et al.2009;Claesson et al.2012) • The presence of particular groups of bacteria may provide health advantages . • Microbes have been shown to enhance metabolism, immune system, cancer resistance, endocrine signaling, and brain function. Some bacteria taxa associated with these benefits include bacteroides,bifidobacterium ,Clostridium cluster XIVa/IV and Lactobacillus (Mills.2011;tremaroli and backed,2012;Hollister et al.2014). • The gut microbiome appears to remain relatively resilient over time ,however, antibiotics use ,travel, and illness can lead to its variation.
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  THE NORMAL GUTMICROBIOTA Fig.4. , Hollister et al. 2014)
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  INDICATIONS OF FMT 1.Mild to moderate rCDI after a second recurrence following treatment with a standard antibiotics(Bakken et al.2011) 2. Moderate rCDI that is not responding to standard therapy after 1 week 3. Severe CDI that is refractory to standard therapy after 48hours 1. The recent U.S guidelines recommend FMT in patients with 3 or more recurrence of CDI, although most clinicians prescribe FMT if CDI recurrence after 2 courses of antibiotics (Mcdonald et al.2017)
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  FMT IN CONDITIONSOTHER THAN CDI 1. Inflammatory bowel disease 2. 3. Irritable bowel syndrome 4. Obesity 5. Metabolic syndrome 6. Type 2 diabetes 7. Fatty liver disease 8. Hepatic encephalopathy
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  CLOSTRIDIUM DIFFICILE INFECTION(CDI) C. difficile is a Gram-positive, anaerobic, spore-forming, and toxin producing bacillus. It is a leading nosocomial infection and its becoming an increasingly virulent and severe epidemic (Miller et al.2011). We have some symptoms of Clostridium difficile infection which are mild watery diarrhea to potentially lethal conditions such as pseudomembranous colitis (Bauer et al. 2011). Antibiotics have been implicated in the pathogenesis of CDI. Fig.5. Clostridium Difficile
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  PROCEDURE OF FMT •FMT carries the possibility of transmitting infectious agents, and therefore rigorous screening tests are recommended to reduce such risk. • Once a donor is selected, blood and fecal samples must be test for pathogens. • FMT workgroup in the U.S recommend using a donor questionnaire that is similar to current protocols for screening blood donors. DONOR EXCLUSION CRITERIA From history the donors may be chosen from family members, intimate partners, friends or unrelated volunteer.
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  Fig.6. PROCEDURE OFFMT
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  DONOR PREPARATION 1. Aspecimen of stool is suspended in tap or bottled water, milk or non- bacteriostatic saline solution, although the latter is presumed to be likely to affect the microbiota of donor stool. 2. Donor stool is then homogenized either by hand stirring and shaking or using a mechanical blender . 3. After suspension with the diluent ,the mixture is filtered through a gauze or coffee filter or strained through a steel strainer to remove large particulates . ADMINISTRATION OF DONOR FECES. It can bebe performed through the lower GI route,including colonoscopy, flexible sigmoidoscopy,rectal tube or retention enema and via the upper GI route such as nasogastric /nasointestinal tube.
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  ADMINISTRATION OF DONORFECES. Google image
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  SAFETY OF FMT Wehave the long and short term adverse events of FMT 1. SHORT TERM Minor effects which are fever and abdominal tenderness that resolved with 2 days post FMT(Vermeire et al.2012). Serious adverse events possibly related to FMT that is upper gastrointestinal tract, bleeding,peritonitis, and enteritis.(Gough.et al.2011;Kassan.et al. 2015). 2. LONG TERM There exist theoretical possibility of unrecognized infectious disease transfer or stimulation of chronic disease e.g obesity, diabetes.
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  REGULATORY ISSUES 1. TheU.S FDA considers stool as a biological product and drugs and mandates physicians to obtain an investigational new drug application (IND) to administer FMT. 2. The FDA has stated that it will allow physicians to use their own discretion in administering ring FMT to patients with CDI that does not respond to conventional therapies (without an IND).
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  FUTURE DIRECTIONS There isincreasing uptake and acceptance for the therapeutic use of FMT, partially due to it’s perception as a ‘natural ‘treatment and it’s relatively inexpensive implementation. (Kelly et al. 2015). In addition , observations from patients treated with FMT for functional bowel disorders have noted improvements in seemingly unrelated comorbidities revealing a possible role for gut microbiota modification in many other conditions. (Borody et al.2012).
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  CONCLUSION FMT is theadministration of fecal matter from a donor into intestinal tract of a recipient and the history started from the 4th century where yellow soup was used in curing food poisoning and falls back to 1958 where Eiseman treated four cases. The human microbiota is estimated to contain 10-100 trillion microbial cells ,the indicate that severe CDI that is refractory to Standard therapy after 48hours and FMT is involved in some other diseases like IBD and IBS. Once a donor is selected, blood and fecal samples must be test for pathogens and it can be performed through the lower GI and the upper GI. The safety of FMT is determined by the short and long term adverse events of it. The U.S FDA considers it as a biological product and drugs and there is an improvement in the patients treated with FMT