2. The Microbiome and Probiotics: Fact and Fiction Ameet Parikh, MD

3. Human Gut microbiome - What is it -What role does it play in health and in disease -Modification of the microbiome to maintain health or treat disease Microbiome

4. Microbiota The microorganisms that live in an established environment Microbiome The full complement of microbes, their genes, and genomes in a particular environment Microbiome

5. The Gut Microbiota -Complex community of microbes – estimated to contain 200 trillion cells -> 1000 diverse microbial species -10 x the number of human cells in our body - Gut microbiome is 150 x larger than the human genome

6. Gut Microbiota

7. Bacteroidetes and Firmicutes make up around 90% of the gut microbiota Each individual harbors his/her own distinctive pattern of gut microbial communities For a given individual, the fecal microbiota remains remarkably stable over a person’s lifetime

8. Prevents colonization by pathogens “Educates the immune system” Metabolic role -Caloric salvage -Produces SCFA Vit K and folate Participates in drug metabolism Activates 5-ASA Deconjugates bile acids Gut Microbiota - Functions

9. Gut Microbiota Colonization of the gastrointestinal tract begins immediately after birth Initial bacterial colonization (normal) starts from a “Germ free” intrauterine environment and is populated through maternal vaginal/fecal flora and oral feeding (breast milk vs formula) Complete adult colonization : by 3 yrs of life

10. Factors affecting Gut Microbiome

12. Alterations in gut microbiota have been linked with FBDMetabolic diseases IBDObesity CDIMalignancy Celiac diseaseType I DM AllergiesNASH AutismDepression Microbiome

13. Does the intestinal microbiota differ in patients with specific disorders (IBS/IBD) from healthy subjects? If the microbiota does differ, is it an important factor in the pathogenesis of the disorder? Gut Microbiota

14. Gut Microbiota - IBD Pathogenesis – linked to inappropriate activation of GI immune system toward the gut microbiota in genetically susceptible hosts &under the influence of environmental factors

15. Gut Microbiota - IBD

16. IBS, functional bloating/constipation/diarrhea Change in gut microbiota – cause abn fermentation of dietary substrates elicit excess stimulation of the mucosal immune system through a ‘leaky gut’ – leads to low grade inflammation, affects gut motor responses & elicits visceral hypersensitivity Decreased Bifidobacterium and Lactobacillus in IBS Gut Microbiota - FBD

17. Gut Microbiota - CDI

18. - Diet - Antibiotics - Prebiotics - Probiotics - Symbiotics - FMT Gut Microbiota

19. Global sales of Probiotics – 21.6 billion dollars in 2010, expected to reach 31.1 billion in 2015 Fastest growing segment of the global dietary supplement & functional food industries People are looking for ‘natural’ or non-drug ways to maintain health or treat disease Probiotics

20. First described by Metchnikoff in 1907

21. Probiotics Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host Prebiotics Nondigestible substances that provide a beneficial physiological effect for the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria

22. Probiotics Synbiotics Products that contain both probiotics and prebiotics

23. Probiotics in the Treatment of Gastrointestinal Disorders Diarrhea Acute infectious Antibiotic-associated C. difficile Lactose Intolerance FBD IBD Ulcerative colitis Crohn’s disease Pouchitis H. pylori Eradication

24. Probiotics

25. Able to survive the passage through the digestive system. Able to attach to the intestinal epithelia and colonize. Able to maintain good viability. Able to utilize the nutrients and substrates in a normal diet. Non pathogenic and non toxic. Capable of exerting a beneficial effect on the host. Stability of desired characteristics during processing, storage and transportation. Characteristics of Effective Probiotics

26. Probiotics – Diarrheal Diseases

27. Probiotics - AAD

28. Antibiotic Associated Diarrhea

31. Probiotics - FBD 10 – 15% of population has IBS pathogenesis – dysmotility, visc hypersensitivity, disturbances in GI flora, and chronic immune activation leading to low grade mucosal inflammation have all been implicated

36. Probiotics - CDAD

39. First Transplant was in November 2013 Performed 62 transplants to date for recurrent CDI Of the elective cases we have had sustained cures in 57/62 first time FMT- 5 relapses occurred 3/5 relapses needed antibiotics after FMT 3 competed 2 nd FMT, no continued issues to date 2 treated with Vanco or Dificid and did not require 2 nd FMT FMT – LGI experience

43. Probiotics - IBD

51. FMT - IBD

53. Much work remains: Is FMT effective and safe in IBD? - Adequately powered trials Ideal recipient? - Genotype - Phenotype: Pouchitis, Proctitis, Post-op prophylaxis, ileal Crohn’s, maintenance of remission, Microbiome - Concomitant meds - Can FMT make some patients worse?

55. Great success story for recurrent CDI Being studied for multiple other conditions – IBD, IBS, Obesity Autism, NASH/Met synd, reversal of multidrug resistance to abx IBD is associated with dysbiosis –More complicated than C. difficile Patients are eager for alternative therapies FMT appears generally “pretty safe” – Infections and disease flares have been reported Therapeutic Manipulation of gut microbiota holds promise & may eventually prove beneficial for other conditions – We must not be overly enthusiastic and remember that this is experimental and unproven therapy. FMT

56. Lachnospiraceae family Faecalibacterium prausnitzii Akkermansia muciniphila Probiotic ecosystems Microbiome - Future

57. “All disease begins in the gut” Hippocrates 460 BC – 370BC “Health is determined by the microbiota in our gut” Hippocrates Gut Microbiome

58. Thank You