Lecture 09 (3 4-2021) euks
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The document provides an overview of the human microbiome, detailing its composition, development, and its critical role in health and disease. It discusses the relationship between the microbiome and various health issues, including obesity and severe acute malnutrition, and emphasizes the stability and adaptability of the microbiome based on lifestyle factors. Key learning goals include understanding the diversity of microbes present, their origins, and the implications they have for human health.
Lecture 09 (3 4-2021) euks
- 1. DIVERSITY OF THE HUMAN MICROBIOME Unit 09, 3.4.2021 Reading for today: Brown Ch. 16, Walter & Ley Reading for next class: Brown Ch. 15 Dr. Kristen DeAngelis Office Hours by appointment deangelis@microbio.umass.edu
- 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. 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. Human microbiome • All microbes in and out of the body 4
- 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 https://commons.wikimedia.org/wiki/File:Staphylococcus_on_catheter.png (cover slide) https://commons.wikimedia.org/wiki/File:Animalcules_observed_by_anton_van_leeuwenhoek_c1795_1228575.jpg 5
- 6. Estimates for the concentration and number of bacterial cells in the body Sender et al. 2016 6
- 7. How many microbes are there? • 1:1 bacteria vs 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 – does not count your blood cells: they are anucleate – Your microbiome is 1-3% of your 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 Martin J. Blaser. "The human microbiome: at the interface of health and disease." Nature Reviews Genetics 13.4 (2012): 260. 7
- 8. Gut microbiome origins http://bit.ly/HumanMicrobiome; https://www.youtube.com/watch?v=Pb272zsixSQ 8
- 9. 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 microbiomes! Walter & Ley, 2011 9
- 11. How 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 11
- 12. Gut microbiome Walter & Ley, 2011 12
- 13. Why is the microbial community of the GI tract so different? • 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 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 13
- 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). 14
- 15. Human Microbiome Project • To characterize the ecology of human- associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats so far • Healthy individuals differ in the taxonomy microbes that occupy habitats such as the gut, skin and vagina • Based on metagenomics, metabolic pathways are consistent among individuals despite variation in community structure HMP Consortium, 2012 15
- 16. Who’s there? • Human microbiome is mostly bacteria but also archaea, fungi and other eukaryotes Spor et al., Nat Rev Micro 2011 16
- 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 17
- 18. Human microbiome – Microbes from all three domains are represented in the human microbiome – Most of the cultured diversity is contained in five phyla (Bacteroidetes, Firmicutes, Actinobacteria, Cyanobacteria, Proteobacteria) – Only Fusobacteria (phylum with very few cultivated members, all symbionts; found in mouth & GI tract) is a common microbiome organisms with few cultured representatives… is this a coincidence? HMP Consortium, 2012 18
- 19. Human microbiome • Archaea – dominant group are the methanogens, particularly Methanobrevibacter smithii and Methanosphaera stadtmanae – No archaeal pathogens are known 19
- 20. 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
- 21. 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. 21
- 22. 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. 22
- 23. 5 Eukaryotic supergroups: • Excavates • Chromalveolates • Plantae • Rhizaria • Unikonts Bacteria Eukarya Euryarchaea Crenarchaea Domain Eukarya Bacteria Eukarya Archaea Archaea Bacteria Eukarya
- 25. Eukaryotes • * You are here. (SK Unikonts, kingdom Opisthokonts) • 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 25
- 26. 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. 26
- 27. Metabolism of the Eukaryotes • Generally heterotrophic or phototrophic • in most cases metabolism is supported by organelles derived from endosymbionts – Mitochondria derived from the Alphaproteobacteria Rickettsia – Chloroplasts derived from the Cyannobacteria – Plastids derived from other eukaryotic phototrophs 27
- 28. 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. 28
- 29. Eukaryotic microbiome: Malassezia spp • Most fungi identified on healthy skin 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 harbors 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. 29
- 30. Eukaryotes Ernst Haeckel’s drawings of radiolarians (rhizaria) A fellow unikont, the slime mold dictyostelium (amoebozoa) A fellow unikont, Sacchromyces cerevisiae (opisthokont) 30
- 31. 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 31
- 32. 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. 32
- 33. How does your microbiome affect health and disease? • We have co-evolved with our microbiomes • 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 33
- 34. Gut microbiome Brussow & Parkinson, 2014 • Gut morphology reflects co-evolution with the microbiome 34
- 35. Gut microbiome • Gut morphology reflects co-evolution with the microbiome – Host digests simple nutrients – Host relies on abilities of microbes to digest complex components & generate short-chain fatty acids (SCFAs) • Most gut metabolites are beneficial – 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 are metabolized by bacteria to antioxidants & anti-cancer compounds, e.g., ellagic acid (in berries & nuts) Walter & Ley, 2011 35
- 36. Gut microbiota can 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 – Hydrogen Sulfide (H2S) is produced from sulfur reducers in high-protein diets Rooks & Garrett, F1000ReportsBiology, 2011 36
- 37. • Probiotics are live microbes that are eaten • The U.S. Food and Drug Administration (FDA) has not approved any probiotics for preventing or treating any health problem. • If you want to change your microbiome… feed it the good stuff! https://nccih.nih.gov/health/probiotics/introduction.htm 37
- 38. 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 – Low pH restricts Gram-negative bacteria growth Smilowitz et al., Annu. Rev. Nutr. 2014 38
- 39. The original prebiotic: breast milk • Human milk contains – higher amounts and more complex structures of soluble oligosaccharides than any other mammalian milk – Antibodies for immune protection • Human Milk Oligosaccharides are prebiotics for beneficial Bifidobacteria • associated with numerous benefits – improved vaccine effectiveness – enhanced gut barrier function – protection from enteropathogen infection 39
- 40. Host lifestyle affects human microbiota on daily timescales 40
- 41. 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. • 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. 41
- 42. A core gut microbiome in obese and lean twins Turnbaugh et al., Nature 2009 42
- 43. A core gut microbiome in obese and lean twins Turnbaugh et al., Nature 2009 43
- 44. 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. 44
- 45. Bacteriotherapy • Fecal microbiome transplants (FMT) • Successful in treating Clostridium difficile infections 45 A pathological specimen showing pseudomembranous colitis, Wikipedia
- 46. 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 46
- 47. Human microbiome and malnutrition A malnourished child with kwashiorkor Trehan et al. NEJM 2013. 47
- 48. Human microbiome and malnutrition • Kwashiorkor, an enigmatic form of severe acute malnutrition (SAM), is the consequence of inadequate nutrients plus additional environmental stress. • 1 million children die annually due to SAM. • 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. 48
- 49. Gut microbiome is a causal factor in kwashiorkor Smith et al. Science. 2013. Mouse model Kwashiorkor Gut communities Healthy Gut communities 49
- 50. 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. • Malawian diet fed to mice with 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. 50
- 51. How is the human microbiome related to health and disease? • Health – Barrier to disease – Gut microbiota production of short-chain fatty acids for nutrition • 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 51
- 52. 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? 52
- 53. 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 53