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Pre Pro Post Biotic Biome Biology Chris Vulpe

micro

NST10, Fall 2013

Microbes and you!

Microbe: tiny living organism, such as bacterium, fungus, protozoan, or virus!

!! A few microbes can cause disease ! !! Cholera, Tuberculosis, Botulism, etc! !! Majority of microbes are beneficial ! !! Food beer, bread! !! Soil regenerate soil, !

!! Human Health microbes are essential for maintaining your health! !

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provide nutrients for crops!

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Human Microbiome Microbes are all over us!

! 10 X more microbial than human cells! ! ~1000 different species of microbes! ! ~3 million microbial genes vs 23,300 human genes! ! 3 lbs of microbes in the gut, ~60% stoool is microbial mass! ! Each body site has unique microbial community!

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

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Human microbiome is obtained from Mother during birth !

Neonatal microbiome similar to Mothers skin microbiome

Neonatal microbiome similar to Mothers vaginal microbiome

Vaginal birth!

Cesarean! birth!

Johnson C L , and Versalovic J Pediatrics 2012;129:950-960

Infant microbiome establishes in first year of life!

Each baby ! is unique!

Increasing similarity to ! Adult Microbiomes!

Palmer C, Bik EM, DiGiulio DB, Relman DA, et al. (2007) Development of the Human Infant Intestinal Microbiota. PLoS Biol 5(7): e177. doi: 10.1371/journal.pbio.0050177 http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0050177

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Gut may not seems like a great place to live ! ! Dark! ! low pH! ! Saliva and Bile! ! Immune system! ! Its moving! No place to hang onto to!! ! Wide variation in food. !

Gut Microbiome!

Cfu = colony forming units

But to many, many, many microbes it is home!

Gut Microbiome Who is there?!

Bacteroides

http://ngm.nationalgeographic.com/2013/01/125-microbes/oeggerli-photography#/05-intestinal-bacteria-670.jpg

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What does the Gut Microbiome do?! Almost everything!!

Forgotten Organ!

Ruminococcus sp. bacteria can be found in significantly high numbers in the gut flora. They break down cellulose in the gut, helping with digestion.!

EMBO reports (2006) 7, 688693

Is My Gut Microbiome the Same as Yours?!

The number and amount of the many different microbes can vary greatly from person to person.

My Gut Species

Your Gut Species

JJ Qin et al. Nature 464, 59-65 (2010) doi:10.1038/nature08821

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Composition of Gut microbiome varies depending on location

Nature Immunology 14, 660667 (2013)

Gut microbiome varies with age!

Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol. 2011;9[4]:281

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A role of gut bacteria that you may be familiar with

Bacteroides thetaiotaomicron bacteria ferments simple carbohydrates in the gut, releasing hydrogen and CO2.

+carbohydrates CO2 and H2

Methanobrevibacter smithii archeabacteria consumes hydrogen gas from Bacteroides and produces methane, which is lost from gut as gas

CH4 Methane Gas

The gut microbiome feeds your gut! (the colon)

short chain fatty acids!

Yum!
Butyrate is the preferred food

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A microbial view of drugs!

H J Haiser, and P J Turnbaugh Science 2012;336:1253-1255

Diet IMPACTS the human microbiome!

Nonstarch polysaccharides (wheat bran) Resistant starch

Nutrition Reviews pages S10-S13, 2 AUG 2012 DOI: 10.1111/j.1753-4887.2012.00499.x http://onlinelibrary.wiley.com/doi/10.1111/j.1753-4887.2012.00499.x/full#f1

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Diet influences gut microbial populations

RED POSITIVE association between dietary component and presence of particular gut bacteria BLUE NEGATIVE Association Between dietary component and presence of particular gut bacteria
G D Wu et al. Science 2011;334:105-108

Both long- and short-term effects. Nutrients affect the composition of the intestinal microbiota.

Distinct microbiome with high-fat, low fiber diet No change in short term With low fat/high fiber diet Longer term diet change ???
U Gophna Science 2011;334:45-46

Distinct microbiome with low-fat, high fiber diet

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Diet can change metabolic function of microbiome Japanese can digest sugars (Porphyrans) in a seaweed (Porphyra)! that is not digestible by other ethnic groups ! Activity screening on natural algal polysaccharides reveals porphyranase activity in Japanese microbiomes.!

J-H Hehemann et al. Nature 464, 908-912 (2010) doi:10.1038/nature08937

Marine bacteria normally have galactanases and porphyranases! Japanese gut bacterium B. plebeius have them too!.! Marine bacteria! enzymes!

Japanese Gut Bacterium! B. plebeius !

Marine bacteria! enzymes!

J-H Hehemann et al. Nature 464, 908-912 (2010) doi:10.1038/nature08937

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The porphyranase gene in the human gut bacteria likely came from marine bacteria

Other marine bacteria genes along for the ride! !

Upstream and downstream of the porphyranase gene (Bp1689), the genome of B. plebeius contains carbohydrate-related genes that share highest identity with proteins used for red-algal galactan degradation in two marine Bacteroidetes.
J-H Hehemann et al. Nature 464, 908-912 (2010) doi:10.1038/nature08937

Gut bacterial microbiota and obesity!

! Distinct microbiota in lean and obese individuals! ! ! Transfer of microbiota from obese to lean people (or mice)! can increase weight ! ! ! Germ free mice resistant to obesity from high fat western diet! ! !
Clinical Microbiology and Infection Volume 19, Issue 4, pages 305-313, 2 MAR 2013 DOI: 10.1111/1469-0691.12172 http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12172/full#clm12172-fig-0001

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Microbiome Changes in Obesity!

!! Obesity changes the relative proportions of Firmicutes vs Bacteroides. ! !! Obese mice AND obese people have more Firmicutes than Bacteroidetes: !
!

!! Chicken or the egg?!

Ley, et al. PNAS. 2005, 102: 11070-75

Gut Flora and Obesity!

Germ free mice control mice (remaining germ free) were changed from low fat diet to Western diet!
Western diet: 41% lipids, 41% carbohydrates (with simple sugars), 18% protein

Mice given normal gut flora ! also had same diet change!

Germ Free mice are resistant to the Western diet! !

Gordon J, et al, PNAS 2007;104:983

Gut flora are responsible for increasing energy production from food!

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The Microbiome: transplant experiments!

!! Germ-free mice given ob/ ob or wild-type flora!
wild type microbiome

Germ Free Mouse

ob/ob microbiome

!! Chow consumption and exercise the same for both groups! !! Both sets had similar starting weight and % BF.! !! The ob/ob microbiota promote host adiposity!
Turnbaugh, et al. Nature 2006; 444:1027

Microbes from people can influence obesity in mice

Please pass the microbiota. Germ-free mice inoculated with microbiota from obese or lean human twins take on the microbiota characteristics of the donor.
A W Walker, and J Parkhill Science 2013;341:1069-1070

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Different Microbiomes in health and disease

Dysbiosis :a state of microbial imbalance in the gut

Unravelling the effects of the environment and host genotype on the gut microbiome. Nat Rev Microbiol. 2011;9[4]:281

Therapeutic modulation of intestinal dysbiosis Pharmacological Research 69 (2013) 75 86

Fecal transplants can cure usually fatal gut infections

43 patients with C.difficile infection 13 patients received vancomycin 17 patients received donor feces 13 patients received vancomycin And bowel lavage (wash) Clostridium difficile

Prolonged antibiotic treatment can result in overgrowth of C.difficile Usually treated with vancomycin but resistance is major problem

93.8 % cured with donor feces

31%! with! Vanco!

http://www.nejm.org/doi/full/10.1056/NEJMoa1205037 http://www.npr.org/blogs/health/2013/06/18/193069110/fda-backs-off-on-regulation-of-fecal-transplants

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PreBiotics!
GalactoOligosaccharides

human milk oligosaccharides

Bovine (cow) milk oligosaccharides

Food ingredient that supports the growth and expression of a beneficial biological property or properties of one or more resident gut microbes. !
Current Opinion in Biotechnology Volume 24, Issue 2 2013 214 - 219

Human milk oligosaccharides mix ! Complex of sugars

Bifidogenic Promote growth of Bifidobacterium sp. Predominant microbes in infants

! produce lactic and acetic acid that controls intestinal pH ! Inhibit growth of pathogenic microbes - help prevent diarrhea

Not to be confused with Biff

Trends Microbiol. 2010 July; 18(7): 298307.

! Support infant immune system

Nutrition Reviews Vol. 67(Suppl. 2):S183S191

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!! Live microorganisms that when ingested provides benefit to the host, either directly through interactions with host cells or indirectly through effects on members of the microbiota.! !! Probiotics touted for many disorders but evidence may be lacking Buyer Beware! !! Multiple studies suggest effectiveness of probiotics in treatment of diarrhea although effect may be moderate. !

Probiotics!

!! Recent review of 28 randomized placebo controlled clinical trials found overall reduction of symptoms by ~35% as compared to no-treatment! !! Different effectiveness depending on cause of diarrhea and particular probiotic used.!

!! Many mechanisms may be involved still unclear!

Competition

Co-Aggregation

Produce antibiotics

Nature Reviews Microbiology 9, 27-38 (January 2011) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials, The Lancet Infectious Diseases, Volume 6, Issue 6, June 2006, Pages 374-382,

The Future: Therapeutic modulation of the gut microbiota

E. Holmes et al., Sci Transl Med 2012;4:137rv6

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Microbiome based treatment of Obesity?

!!Diet to manipulate flora?! !!Prebiotics & Probiotics? ! !!Stool transplants?!

Nutrition, Best Practice the & gut microbiome Research Clinical and the Gastroenterology metabolic syndrome Volume 27, Issue 1 2013 59 - 72

Resources ! The Gut Microbiota ! http://www.sciencemag.org/site/special/ gut_micro/ ! Human Microbiome Science: Vision for the Future ! http://www.genome.gov/27554404 ! Staying Healthy May Mean Learning To Love Our Microbiomes ! http://www.npr.org/blogs/health/ 2013/07/22/203659797/staying-healthy-maymean-learning-to-love-our-microbiomes ! http://protomag.com/assets/gut-microbiota-ournative-flora

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