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Lecture 09 (4 24-2018) euks

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Unit 9: Human Microbiome
LECTURE LEARNING GOALS
1. Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region.
2. Describe the domain eukarya. List the five superkingdoms and a few notable species.
3. Explain how the human microbiome is related to health and disease.

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Lecture 09 (4 24-2018) euks

  1. 1. DIVERSITY OF THE HUMAN MICROBIOME Unit 09, 4.24.2018 Reading for today: Brown Ch. 16, Walter & Ley Reading for next class: Brown Ch. 15 Review Session: tbd … please Doodle your preference! Final Exam Wed May 9, 2018, 10:30 am – 12:30 pm, 222 Morrill 2 Dr. Kristen DeAngelis Life Science Labs (LSL) N435 Office Hours Tu & Th 12:30 to 1:30 pm OR by appointment (RSVP appreciated) deangelis@microbio.umass.edu, 413-577-4669 1
  2. 2. Unit 9: Human Microbiome LECTURE LEARNING GOALS 1.  Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region. 2.  Describe the domain eukarya. List the five superkingdoms and a few notable species. 3.  Explain how the human microbiome is related to health and disease. 2
  3. 3. Unit 9: Human Microbiome LECTURE LEARNING GOALS 1.  Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region. 2.  Describe the domain eukarya. List the five superkingdoms and a few notable species. 3.  Explain how the human microbiome is related to health and disease. 3
  4. 4. Human microbiome •! All microbes in and out of the body 44
  5. 5. Human microbiome •  Collection of microbes in and on your body •  Wherever the human body is exposed to the outside world, there is a microbial community. –  Even your GI tract is “outside” technically –  Communities are shaped by their environment… –  Communities also shape their environment •  Our microbiome helps us extract energy and nutrients from our food, and helps to outcompete or inhibit pathogens. •  Your microbiome is an essential organ, like the skin –  You cannot live without it –  You take it for granted until it’s broken h"ps://commons.wikimedia.org/wiki/File:Staphylococcus_on_catheter.png   h"ps://commons.wikimedia.org/wiki/File:Animalcules_observed_by_anton_van_leeuwenhoek_c1795_1228575.jpg  
  6. 6. Estimates for the concentration and number of bacterial cells in the body Sender et al. 2016
  7. 7. How many microbes are there? •  1013 bacteria vs 1013 human cells –  Ratio of bacteria to human cells used to be 10:1 BUT new paper on Revised estimates for the number of human and bacteria cells in the body suggests 1:1 –  1013 human cells (which does not count your blood cells, because they are anucleate) •  1-3% body mass •  The bulk of your microbiome is in the colon, which can fluctuate from 1013 – 1014 bacteria •  The highest concentrations of cells is a tie between colon & teeth Cho,  Ilseung,  and  MarJn  J.  Blaser.  "The  human  microbiome:  at  the  interface  of  health  and   disease."  Nature  Reviews  Gene/cs  13.4  (2012):  260.    
  8. 8. Model of the acquisition, in situ evolution, and community assembly of the gut microbiota a.! Efficient vertical transmission from parent to offspring b.! Inefficient vertical transmission from parent to offspring Walter & Ley, 2011
  9. 9. Gut microbiome •  Small intestine microbes interact with the host immune system •  Two extreme scenarios of vertical transmission from parent to offspring: (a) Efficient vertical transmission –  Niches fill quickly by colonization of microbes that are preadapted. –  Adaptation to physiological differences in the niche environment of individual animals is facilitated by in situ evolution of early colonizers. (b) Inefficient vertical transmission –  Colonization of the next generation relies on horizontal transmission or dispersal. –  Immigration is slow, and in situ evolution/adaptation of early colonizers can occur more rapidly than colonization Walter & Ley, 2011
  10. 10. Gut microbiome origins http://bit.ly/HumanMicrobiome; h"ps://www.youtube.com/watch?v=Pb272zsixSQ  
  11. 11. Gut microbiome •  Development of the gut microbiome –  Baby microbiomes are variable until they are about 2 years old •  https://www.youtube.com/watch?v=Pb272zsixSQ –  Colonization history impacts microbial community composition & diversity –  Environmental & stochastic factors affect community composition & diversity –  Twins may have different microbial communities! Walter & Ley, 2011
  12. 12. HMP Consortium, 2012
  13. 13. Why is the microbial community of the GI tract so different? •  There are several ways by which the human host restricts bacterial biomass in the stomach and SI –  Bile salts are strongly bacteriocidal –  pH as low as 2 inhibits most microbial growth –  Immunoglobulin (Ig), specifically IgA recognizes the dominant microbes present –  Epithelial cells produce antimicrobial compounds (e.g., defensins, cathelicidins, and C-type lectins), some constitutively and some activated by the presence of bacteria
  14. 14. Human Microbiome Project HMP Consortium, 2012 •  Despite variation in community structure (phyla, top), metagenomic carriage of metabolic pathways was stable among individuals (metabolic pathways, bottom).
  15. 15. Human Microbiome Project •  To characterize the ecology of human- associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far •  Healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina •  Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure HMP Consortium, 2012
  16. 16. Who’s there? •  Human microbiome is mostly bacteria but also archaea, fungi and other eukaryotes Spor et al., Nat Rev Micro 2011
  17. 17. Human microbiome •  Bacteria – Bacteroidetes dominate gut communities – Firmicutes dominate esophagus and vagina – Actinobacteria live in the mouth, where they make biofilms (plaque) – Cyanobacteria live in the hair – Fusobacteria (phylum with very few cultivated members, all symbionts) – Proteobacteria
  18. 18. Human microbiome •  Archaea – dominant group are the methanogens, particularly Methanobrevibacter smithii and Methanosphaera stadtmanae – No archaeal pathogens are known
  19. 19. Human microbiome •  Eukaryotes – Mostly fungi, e.g., yeasts like Candida spp. – Malassezia spp. – Yeasts are also present on the skin, where they consume oils secreted from the sebaceous glands
  20. 20. Activity for Review of ! Unit 09.1 Human microbiome •! How do we get our microbiomes?" •! How does the human microbiome functional diversity compare to the phylogenetic diversity. " 20
  21. 21. Unit 9: Human Microbiome LECTURE LEARNING GOALS 1.  Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region. 2.  Describe the domain eukarya. List the five superkingdoms and a few notable species. 3.  Explain how the human microbiome is related to health and disease. 21
  22. 22. Eukaryotes * Excavates     Chromalveolates     Plantae   Unikonts   Rhizaria  
  23. 23. Eukaryotes •  Five major superkingdoms •  The superkingdoms derived from a single radiation (common ancestor) •  How the superkingdoms are related is not clear and subject to intense debate •  Within the superkingdoms are sometimes called kingdoms, but there is little consistency among the taxonomy
  24. 24. Eukaryotes Five major superkingdoms 1.  Excavates – flagellated single-celled eukaryotes, pathogens 2.  Chromalveolates – mostly phototrophic algae, diatoms 3.  Plantae –plants, including land plants, green and red algae; all have plastids (chloroplasts) derived from cyannobacteria 4.  Rhizaria – all unicellular eukaryotes, very diverse 5.  Unikonts*- include Amoebozoa and Opisthokonts, which have two main groups, fungi & animals * You are here.
  25. 25. Metabolism of the Eukaryotes •  Generally heterotrophic or phototrophic, but in most cases this is supported by organelles derived from endosymbionts – Mitochondria derived from the Alphaproteobacteria Rickettsia – Chloroplasts derived from the Cyannobacteria – Plastids derived from other eukaryotic phototrophs 25
  26. 26. Eukaryotic microbiome: Malassezia spp M. furfur in skin scale from a patient with tinea versicolor. Notice the budding and slightly filamentous growth, characteristic of yeasts.
  27. 27. Eukaryotic microbiome: Malassezia spp •  Most fungal organisms identified on the healthy skin by molecular typing and culture- based data resemble Malassezia spp. •  Malassezia is a yeast, which is a non- filamentous fungus •  In one study, Malassezia spp. were calculated to constitute 53–80% of the total skin fungal population, depending on the skin site •  retroauricular crease harbours the highest proportion of these microbes, where they consume oils secreted from the sebaceous glands Grice  and  Segre,  Nat  Rev  Microbiol.  2011  April  ;  9(4):   244–253.  doi:10.1038/nrmicro2537.    
  28. 28. Eukaryotic microbiome: Candida albicans (Yeast)
  29. 29. Eukaryotic microbiome: Candida (Yeast) •  C. albicans is a diploid fungus populating the human body worldwide, inhabiting 80% of everyone's intestinal tract, colon, and mouth with no problems. •  It is unusual in that it is polymorphic, meaning it can grow as both a yeast and as filamentous cells. •  It is a popular cause of oral and vaginal infections ("thrush") , but is easily treated with common anti-fungals in people who are not immunocompromised. h"ps://microbewiki.kenyon.edu/index.php/Candida_albicans  
  30. 30. Eukaryotes 2*$7;c1/'./5d$;021,-*3$;(O; 210-(512-1*$;R2!-Y12-1T; <;O/55(,;9*-.(*7G;7!/;$5-)/;)(50; 0-'78($7/5-9);R1)(/=(Y(1T; <;O/55(,;(#-$7!(.(*7G; 1"002%3450&,'0&%&)*,*"&'
  31. 31. Eukaryotes •  Sacchromyces cerevisiae –  A fellow opisthokont –  Earliest evidence of humans using yeast to ferment food is an alcoholic beverage of rice, fruit and honey from 7000 BC •  Dictyostelium discoideum –  A fellow unikont, aka the slime mold –  An amoebozoa that lives in soil –  Related to Physarum polycephalum, the first non- human scholar in residence, Hampshire college •  Ernst Haeckel’s drawings of radiolarians –  Rhizaria are unicellular eukaryotes, very diverse
  32. 32. Activity for Review of ! Unit 09.2 Eukarya" Match the eukaryotic superkingdom to its major characteristics" 1.! Excavates" 2.! Chromalveolates" 3.! Plantae" 4.! Rhizaria" 5.! Unikonts" a)! mostly phototrophic algae, diatoms" b)! flagellated single-celled eukaryotes, pathogens" c)! all unicellular eukaryotes, very diverse" d)! include Amoebozoa and Opisthokonts, which have two main groups, fungi & animals" e)! plants, including land plants, green and red algae; all have plastids (chloroplasts) derived from cyannobacteria" 32"
  33. 33. Unit 9: Human Microbiome LECTURE LEARNING GOALS 1.  Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region. 2.  Describe the domain eukarya. List the five superkingdoms and a few notable species. 3.  Explain how the human microbiome is related to health and disease. 33
  34. 34. How does your microbiome affect health and disease? •! We have co-evolved •! Antibiotics, probiotics and prebiotics –! change the microbiome –! but the system is dynamic •! Some diseases can be treated by targeting the microbime –! Obesity –! C. dif. or CDI –! Severe acute malnutrition
  35. 35. Gut microbiome Brussow & Parkinson, 2014 •  Gut morphology reflects co-evolution with the microbiome
  36. 36. Gut microbiome •  Gut morphology reflects co-evolution with the microbiome – Human digestive tract is partitioned – Segregates host digestive processes from most microbial biomass. – Host digests simple nutrients; a main component of the modern diet – Host relies on abilities of microbes to digest complex components & generate short- chain fatty acids (SCFAs) Walter & Ley, 2011
  37. 37. Gut microbiome Walter & Ley, 2011
  38. 38. Human Gut Microbiome •  Colon has the most cells per body –  ~1014 total cells –  Next most abundant is dental plaque (1012), saliva (1011), skin (1011), and small intestines (1011) –  Stomach only has 107 •  The human digestive tract is partitioned to segregate the host digestive processes from most of the microbial biomass, so that the host has the first shot at dietary substrates. •  The human gut microbiota in their collective metagenome encodes 150 times more genes than are present in the human host genome. •  The gut microbiome has the biosynthetic capacity to break down a greater range of plant polysaccharides; microbial fermentation provides roughly 10% of daily energy from a Western diet
  39. 39. Gut microbiota make metabolites that are beneficial to the host •! Fermentation products (SCAs) –! Butyrate – energy source for gut wall epithelial cells –! Acetate – quells overactive immune response; may protect host from E. coli infections –! Proprionate – interacts with T cells, influences immune response •! Polyphenols metabolized by bacteria to antioxidants & anti-cancer compounds –! ellagic acid (in berries & nuts) Rooks & Garrett, F1000ReportsBiology, 2011
  40. 40. Gut microbiota make metabolites that are detrimental to the host •! Damaging to host DNA –! Heterocyclic amines (HCAs) in char are converted by gut microbes to electrophilic derivatives –! Sulfur reducers convert sulfur in high-protein diets to H2S Rooks & Garrett, F1000ReportsBiology, 2011
  41. 41. •! Probiotics are live microbes that are eaten •! Although some probiotics have shown promise in research studies, strong scientific evidence to support specific uses of probiotics for most health conditions is lacking. •! The U.S. Food and Drug Administration (FDA) has not approved any probiotics for preventing or treating any health problem. https://nccih.nih.gov/health/probiotics/introduction.htm
  42. 42. The original prebiotic: mother’s milk •! Humans cannot digest many human milk oligosaccharides! •! Selective for Bifidobacteria (phylum Actinobacteria) –! Activity of this group lowers gut pH –! Makes it more difficult for Gram-negative bacteria to grow Smilowitz et al., Annu. Rev. Nutr. 2014
  43. 43. The original prebiotic: breast milk •  Human milk contains –  Antibodies for immune protection –  higher amounts and more complex structures of soluble oligosaccharides than any other mammalian milk •  Human Milk Oligosaccharides (HMOs) are prebiotics for beneficial Bifidobacteria •  associated with numerous benefits –  improved vaccine –  enhanced gut barrier function –  protection from enteropathogen infection
  44. 44. Host lifestyle affects human microbiota on daily timescales
  45. 45. Host lifestyle affects human microbiota on daily timescales •  The human microbiome is generally stable, but can be quickly and profoundly altered •  Over 10,000 measurements of human wellness and action were linked to the daily gut and salivary microbiota dynamics of two individuals over one year. •  Overall microbial communities to be stable for months. •  Rare events in each subjects’ life rapidly and broadly impacted microbiota dynamics. –  Travel –  Enteric infection •  Changes in host fiber intake positively correlated with next-day abundance changes among 15% of gut microbiota members.
  46. 46. A core gut microbiome in obese and lean twins Turnbaugh et al., Nature 2009
  47. 47. A core gut microbiome in obese and lean twins Turnbaugh et al., Nature 2009
  48. 48. Human microbiome and obesity Community sequencing of total gut microbiota taken from obese and lean twins show substantial differences in their compositions. Obesity is associated with phylum-level differences in the microbiota, a significantly reduced bacterial diversity, and an increase in the population expression of enzymes which result in an increased efficiency of calorie harvest in the diets of the obese twins. •  Figure 1 | 16S rRNA gene surveys reveal familial similarity and reduced diversity of the gut microbiota in obese individuals. •  a, Average unweighted UniFrac distance (a measure of differences in bacterial community structure) between individuals over time (self), twin pairs, twins and their mother, and unrelated individuals (1,000 sequences per V2 data set; Student’s t-test with Monte Carlo; *P<10^5; **P<10^14; ***P<10^41; mean +/- s.e.m.). •  b, Phylogenetic diversity curves for the microbiota of lean and obese individuals (based on 1–10,000 sequences per V6 data set; mean +/- 95% confidence intervals shown).
  49. 49. Bacteriotherapy •  Fecal microbiome transplants (FMT) •  Successful in treating Clostridium difficile infections 49 A  pathological  specimen  showing   pseudomembranous  coliJs,  Wikipedia  
  50. 50. Bacteriotherapy •  Aka fecal microbiome transplantation, or fecal transplant •  Transfer of stool from a healthy donor into the gastrointestinal tract to treat Clostridium difficile infections •  Successful in treating a range of gastrointestinal diseases, including colitis, constipation, irritable bowel syndrome, and neurological conditions such as multiple sclerosis and Parkinson's 50
  51. 51. Human microbiome and malnutrition A malnourished child with kwashiorkor Trehan et al. NEJM 2013.
  52. 52. Human microbiome and malnutrition •  Kwashiorkor, an enigmatic form of severe acute malnutrition (SAM), is the consequence of inadequate nutrients plus additional environmental insults. •  Severe acute malnutrition contributes to 1 million deaths among children annually. •  In this randomized, double-blind, placebo- controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in ready-to-use therapeutic food (RUTF) for the outpatient treatment of uncomplicated severe acute malnutrition.
  53. 53. Gut microbiome is a causal factor in kwashiorkor Smith et al. Science. 2013. Mouse model Kwashiorkor Gut communities Healthy Gut communities
  54. 54. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor •  Fecal communities from several discordant pairs were each transplanted into gnotobiotic mice •  Mice were then given a representative, nutrient- deficient Malawian diet followed by RUTF (ready- to-use therapeutic food) and then the Malawian diet. •  The combination of a Malawian diet and a kwashiorkor microbiome produced marked weight loss in the gnotobiotic mice. •  These findings implicate the gut microbiome as a causal factor in kwashiorkor and suggest that additional nutritional support may be required to correct persistent metabolic defects arising from microbiome dysfunction in malnourished children.
  55. 55. How the human microbiome is related to health and disease. •  Health –  Barrier to disease –  Gut microbiota production of short-chain fatty acids •  Disease –  Gut microbiota also produces Heterocyclic amines (HCAs) and hydrogen sulfide (H2S) –  Obesity has a distinct microbiome –  Severe acute malnutrition can sometimes be helped using antibiotics 55
  56. 56. Activity for Review of ! Unit 09.3 •! Compare the mechanism of action for probiotics and prebiotics. Which is proven to be effective in changing the microbiome?" 56
  57. 57. Unit 9: Human Microbiome LECTURE LEARNING GOALS 1.  Describe the human microbiome: how many microbes there are, how you get your microbiome, who’s there, and how it changes over time and by region. 2.  Describe the domain eukarya. List the five superkingdoms and a few notable species. 3.  Explain how the human microbiome is related to health and disease. Next class is Unit 10: Diversity of Permafrost Reading for next class: Brown Ch. 15 57

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