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The Human Microbiome Christine Rodriguez, Ph.D. Harvard Outreach 2012 Summer 2012 Workshop in Biology and Multimedia for High School Teachers Microbes are all over us http://www.outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx 11/4/16, 8=29 AM Page 1 of 22

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The Human MicrobiomeChristine Rodriguez, Ph.D.

Harvard Outreach 2012

Summer 2012 Workshop in Biology andMultimedia for High School Teachers

Microbes are all over ushttp://www.outreach.mcb.harvard.edu/Microbiome/download/Microbiome.pptx 11/4/16, 8=29 AM

Page 1 of 22

Summer 2012 Workshop in Biology andMultimedia for High School Teachershttp://commons.wikimedia.org/wiki/File:Man_shad

ow_-_upper.png

Thousands of different species on the skin aloneSome thrive on dry patches of the elbow, othersthrive in moist environment of armpit

There are millions of microbes persquare inch on your body

It is estimated that there are more microbes inyour intestine than there are human cells in yourbody!

What is the Human Microbiome?

Microbe: tiny living organism, such as bacterium,

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Summer 2012 Workshop in Biology andMultimedia for High School Teachers

fungus, protozoan, or virus

Microbiome: collectively all the microbes in thehuman body; a community of microbes

Biofilm: a community of microbes that livetogether on a surface

Microbes in the Human Microbiome include speciesfrom each major domain

“Extremophile”Archaebacteria

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http://commons.wikimedia.org/wiki/File:Tree_of_life.svg

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Bacteria

Fungi

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What features distinguish themicrobial domains?

Generalizedbacteria andarchaebacteriacell

Bacteria• Have no nucleus or membrane bound organelles• Often sphere (cocci) or rod (bacillus) shape, but others as well

Archeabacteria• Have no nucleus or membrane bound organelles• Can look similar to bacteria or drastically different shapes,

such as flat and square• Have some metabolic similarities to eukaryotes

Eukaryotes• Have a true nucleus and membrane bound organelles

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http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=BACT003B&File_type=GIF

http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=CELL006B&File_type=GIF

Generalizedeukaryotic cell

• Wide variety of shapes. For this presentation, we will focus on fungi• Fungi are unique since they have a cell wall and form spores during

reproduction

Microbes are normally found in andon the human body

The following sites are “hotspots” for microbial life

Summer 2012 Workshop in Biology and

Let’sexplore

these fiveregions

Some microbes are native,normally found in the body

Some microbes areintroduced, suddenlyarriving at a new residence inthe body

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Multimedia for High School Teachershttp://nihroadmap.nih.gov/hmp/

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What’s Happeningin the Nose?

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There is a delicate balance of microbes that are maintained to keep that environment healthy.Weakened immune systems can throw off that balance and allow the wrong microbes togrow out of control.

Inflammationfrom viralinfection andallergic reactions

Inhaled medicinesand oral antibiotics

Cilia and mucouslining trap inhaledmicrobes

The nose is aprimary defenderagainst inhaledpathogens

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The interior lining of the nose contains mucous secreting glands. A wide variety ofmicrobes are normally found there. Here’s a few:

http://commons.wikimedia.org/wiki/File:Human-nose.jpghttp://en.wikipedia.org/wiki/File:Staphylococcus_epidermidis_01.png

Staphylococcus epidermidis bacteria forms a biofilm thatcoats the mucosal lining

Staphylococcus aureus bacteria is fine when kept undercontrol by a protease found in S. epidermidis, but if left togrow out of control, S. aureus can become pathogenic andcause infection

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Nose

Aspergillus fungal spores are often inhaled

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through the nose. If the immune systemfails to clear these, mold can grow in thelungs

http://en.wikipedia.org/wiki/File:Aspergillus.jpg

Corneybacterium accolens bacteria is rarely a pathogen,but if it enters the bloodstream due to a torn bloodvessel, it can cause serious infections

http://en.wikipedia.org/wiki/File:Corynebacterium_ulcerans_01.jpg

What’s Happening inthe Oral Cavity?

A wide varietyof microbesregularly enterthe oral cavity saliva, pH,

Brushing and flossing teethclears some built up biofilm

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temperature, immunesystem prevent manyspecies from surviving

Oral antibioticsinhibit growth

Symbiosis of the oral microbes that are able to survive these conditions form an elaboratescaffold that lives on the tooth enamel and at the interface with the gums. It forms a barrierfor incoming bacteria.

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Oral CavityThe oral cavity has a wide variety of microbes normally found there. Here’s a few:

Streptococcus mitisbacteria typically forms a

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http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg

Fusobacterium sp.bacteria is a largerbacteria that helpsform a scaffold formany other bacteriain the oral biofilm

biofilm on the hardenamel surfaces of theteeth. If gums getinflamed, it can enter thebloodstream and causeinfection

Oral Cavity

Prevotella sp. bacteria have natural antibiotic resistancegenes. They can attach to epithelial cells or other bacteriaand cause larger infections in inflamed areas.

Candida albicans fungus can cause oral infection known asthrush

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http://en.wikipedia.org/wiki/File:Teeth_by_David_Shankbone.jpg

http://microbewiki.kenyon.edu/index.php/File:P_ruminicola.jpg

http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg

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What’s Happeningon the Skin?

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There are several skinenvironments: oily, dry,moist. Some microbesprefer one over another.

The skin has naturaldefenses includingslightly acidic sweat andantimicrobial peptides.

Microbes hide in crevicesto recolonize skin afterwashing with soap

Antibiotic washes andoral antibiotics disturbnormal balance ofmicrobes on the skin

There is a normal balance of microbes on the skin that protect introduced microbes fromharming us. Damaged skin gives opportunities for microbes to invade the bloodstream andcause serious illness.

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Skin

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• Propionibacterium acnes bacteria colonizes healthy pores, but if poresbecome clogged, it grows out of control

• Staphylococcus epidermidis bacteria normally colonizes on the skin. But whenP. acnes clogs pores, S. epidermidis also grows out of control in the infectedpores

• Staphylococcus aureus bacteria can also infect clogged pores like Staphepidermidis. Even worse, many antibiotic resistant strains of Staph aureusmake it difficult to treat the infection.

Skin

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Trichophyton and Microsporum fungi feast on keratin in the skinand cause ringworm fungal infections

http://en.wikipedia.org/wiki/File:Yeartinfection.JPG

What’s Happeningin the Gut?

Major barriers for microbes entering the gut:• low pH• Saliva and Bile• Immune system

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• Finding a place to attach to intestinal wall• Surviving a widely varied diet

For those microbes that manage to colonize the gut:• gut flora perform regular tasks of digestion, vitamin production, many others• Gene transfer between the myriad of species in the gut can generate new

combinations of drug resistant “superbugs”

GutBacteroides thetaiotaomicronbacteria ferments simplecarbohydrates in the gut,releasing hydrogen and CO2.

+ carbohydrates

CO2 and H2

Methanobrevibacter smithiiCH4 Methane

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archeabacteria consumes hydrogengas from Bacteroides andproduces methane, which is lostfrom gut as “gas”

Gas

Gut

Ruminococcus sp. bacteria can be found in significantlyhigh numbers in the gut flora. They break down cellulosein the gut, helping with digestion.

Helicobacter pylori bacteria has a helical shape and colonizes thestomach and upper G.I. tract. It is known to be a major cause ofstomach ulcers, although many with H. pylori do not get ulcers.

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http://microbewiki.kenyon.edu/index.php/File:G_reaction1.jpghttp://commons.wikimedia.org/wiki/File:Helicobacter_pylori_diagram.png

What’s Happening in theUrogenital Tract?

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Urinary system almoststerile due to urea andother chemicals

Urine often flushesout microbes that findtheir way in

Introducing a catheter intothe urethra can introducemicrobes directly into thebladder, where a biofilm cangrow and cause bladderinfection

The vagina has a low pH due to Lactobacillus secreting lactic acid and hydrogen peroxide.Let’s explore the microbiome of this region further.

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Urogenital

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Lactobacillus and vaginal epithelialcell

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Lactobacillusnormally maintainlow pH while otherspecies are kept insmall numbers inthe vagina If Lactobacillus

decreases fromantibiotics…

Candida albicanscan take over andcause a yeastinfection

http://en.wikipedia.org/wiki/File:Candida_albicans_2.jpg

G. vaginalis and vaginal epithelialcell

Gardnerella vaginaliscan grow too muchand cause bacterialvaginosis.

Urogenital

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The urinary tract is normally sterile due to urine flushing out the tract.

But, Escherichia coli from GI tract can infect urinary tract due to poor hygieneand contamination from nearby GI tract opening.

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Urine sample infected with E.coli

Urine sample infected with E.coli

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Interplay Between Medicine and Microbes

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Antibiotics

Kills infectious bacteria but also disruptsnatural flora. Can result in yeastinfections, digestive problems, etc.

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Chemotherapy drugs

Gut flora has been shown to modify somedrugs during metabolism. This causesmany side effects, including upsetstomach.

Use of Antimicrobial ProductsHow many do we really need?

But do we need someWill this allow “superbugs”that can barely survive these

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Products kill germsto reduce infection

natural exposure togerms to keep ournormal flora around?

treatments to grow andbecome more prevalent…causing problems for thefuture?

Is My Gut Microbiome theSame as Yours?

The number and amountof the many differentmicrobes can varygreatly from person toperson.

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Relative amounts of species

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The Microbiome of one personcan be different than others inspecies and relative amounts

Research in the Human MicrobiomeProject is starting to identify the relativeamount of each microbe present atdifferent locations in the body.

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So many new questions to answerabout the Human Microbiome…

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How does the gut floramodify drugs, andhow can we minimizeside effects?

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Why does my gut flora lookdifferent than yours? Howdoes that affect obesity,food allergies, and ability tofight disease?

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Are we making germs moreresistant to anitmicrobials?What happens when thegerms are resistant to all ofthe drugs in our arsenal?

What do you want toknow?

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