2020-08-27-grand-rounds.md (3107B)
1 # Microbiome 2 3 Vincent B Young MD PhD, Ann Arbor 4 5 Microbiome: community of microbes and environment they inhabit 6 7 Microbiota: the microbes themselves 8 9 Focus on C. Diff 10 11 2-3% of healthy outpts have identifiable, toxin-producing C. Diff 12 13 "Antibiotic Associated Colitis" 1977 papers that first described C. Diff related to abx, using hamsters as a model organism. 14 15 "An Epidemic, Toxin Gene-Variant Strain of Clostridium difficile" 2005 NEJM 16 17 C diff dx: PCR/LAMP, glutamate dehydrogenase testing (GDH) two vs three step, EIA for toxins. 18 19 Controversy: Nucleic acid amplification tests (NAAT) cannot distinguish colonization vs infx (NAAT does detect toxin gene). 20 21 20-30% of pts will test + for NAAT during hospitalization (?colonization, spore passing through). 22 23 Controversy: should we use the most sensitive test (NAAT) to find even colonization, to control spread? 24 Or use toxin tests up front, to catch the cases severe enough to produce detectable toxin? (i.e. use a purposefully less sensitive test that is possibly more specific for more severe dz) 25 26 Classifying severe/complicated CDI 27 - Severe: WBC >15k, Cr >1.5x normal, absolute serum Cr >1.5 if no baseline available 28 - Fulminant: hypotn, shock, ileus, toxi megacolon 29 - Recurrent: 2-8wks from last positive specimen OR clinical response 30 31 Studying microbiome 32 - Anatomy 33 - structure: "who is there?" 34 - Physiology: 35 - actual function: "what is it doing?" 36 - potential function: "what can it do?" 37 38 - 75-80% of tx cases do not recur; 20-25% of cases recur and have worse outcomes. 39 - theory: pts never return to normal microbiota, hence if restore normal microbiota -> cure 40 41 42 - Hx fecal tx (Fecal Microbiota Transplantation, FMT) 43 - Pliny the Elder: fermented milk and fecal tx 44 - Ge Hong: 4th C 45 - another guy whose name I didn't catch: "yellow soup" == poop supernatant 46 - surgeons in 50s: successful fecal tx for abx-associated 47 - 2013 NEJM: 94% success rate for FMT (16pts), 30% vanco, trial ended early 48 49 - Prior to FMT, community is "less diverse" than donors 50 - FMT results in transfer of community structure to pts 51 - Structure does NOT predict function - some pts who do *not* recover do have more diverse micriobiota, and some pts who *do* recover remain less diverse 52 53 Microbiome -> metabolome, and metabolome significantly contributes to generation of spores vs inhibition of infx 54 55 Mice != humans, mouse microbiome != human microbiome. 56 Human feces known to be effective in tx CDI in humans is not effective in tx recurrent CDI in mice. 57 Mouse FMT restores bile acid metabolism in mice, thought to be the main mxn. 58 59 Jenna Wiens, PhD: ML for microbiome. 2018 Infx ctl and hosp epi, "A Generalizable, Data-Driven Approach to Predict Daily Risk of..." 60 61 A generalizable approach vs a generalizable model. 62 YES. 63 (You can feed hospital-specific data to the same code, with some variation in preprocessing, and have a new model using a generalizable approach). 64 65 Wiens now doing prospective work - YES again. 66 67 68 Next steps 69 - moving from association to causation 70 - precision medicine that includes host genome and microbiota genomes, etc.