Is the microbiome really an important player in … · Is the microbiome really an important player...
Transcript of Is the microbiome really an important player in … · Is the microbiome really an important player...
![Page 1: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/1.jpg)
Is the microbiome really an importantplayer in human disease?
Karen Madsen, PhDUniversity of Alberta
![Page 2: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/2.jpg)
Microbiomania – not a new phenomena
Eclectic Medical Journal 1898
![Page 3: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/3.jpg)
Publications 2000-2014
Probiotics
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
Microbiome
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
![Page 4: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/4.jpg)
New technologies…
Culture based Whole genome sequencing
![Page 5: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/5.jpg)
![Page 6: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/6.jpg)
Internet 2015
All diseases and humanbehaviour are influenced
by gut microbes!
Therefore, fix yourmicrobes and you willcure your disease and
change your life!
GenesX
![Page 7: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/7.jpg)
Jonathan Eisen blog
Attraction to partners and relationship success is determined byfinding a partner with similar microbiomes to oneself….
And that if the microbiome in a kissing partner is a match thisleads to bliss and addiction
if the bacteria don’t align with your microbes, you actuallyfeel disgust and revolt
Which has led to things like this interview onCBC Fresh Air….
![Page 8: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/8.jpg)
Host microbiota and health
![Page 9: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/9.jpg)
Jeremiah J. Faith et al. PNAS 2015;112:633-640
Genetic and Microbial Inheritance
• Microbial inheritance couldinvolve acquisition of one or anumber of effector strains thatindividually or collectivelymodulate risk of developingcomplex diseases
![Page 10: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/10.jpg)
Model of Microbial Inheritance
Probability that the gut of any individual is colonized with aparticular strain
P(transmission) = depends on factors such as its ability to surviveenvironmental insults and competitiveness
P(access) – depends on microbes abundance in the community aswell as hygiene, frequency of contact with and healthy status
P(resistance) – depends on the current composition of thepotential recipients microbiota
![Page 11: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/11.jpg)
Jeremiah J. Faith et al. PNAS 2015;112:633-640
Changing microbial colonization throughout life
![Page 12: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/12.jpg)
PNAS 2011:108(Suppl 1):4578
Succession of microbes in an infant
Fever
Introductionof formulaand food
![Page 13: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/13.jpg)
In 2011, we were divided into 3 enterotypes!
(Based onsequencingabout 300people…..)
![Page 14: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/14.jpg)
Enterotype 1= High Bacteroides
Enterotype 2= High Prevotella
Enterotype 3= High Ruminococcus
Arumugam et al. Nature 473, 173-180. 2011
![Page 15: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/15.jpg)
2014: Revision: Diet is the main determinant ofgut microbial composition
Voreades et al. Front. Microbiol. Sept 22, 2014
![Page 16: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/16.jpg)
Jeremiah J. Faith et al. Science 2013;341:1237439
Stability of Microbiota over Time
• Followed 30 individuals up to 5 years• Analyzed microbiota at a strain level• Found ~30% of strains shared between unrelated individuals
![Page 17: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/17.jpg)
Microbiome science needs a healthy dose ofskepticism….
• Do microbiome studies showcausation or just correlation?
• Are changes in microbial compositionbiologically relevant?
• Could anything else explain theresults?
Hanage WP (2014) Nature 512:247-8
![Page 18: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/18.jpg)
CORRELATION CAUSATION
Nature 178:488. 2012
![Page 19: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/19.jpg)
MJ Claesson et al. Nature 000, 1-7 (2012) doi:10.1038/nature11319
Living in long-term care resulted in a poorer diet,worse health, and altered microbiome
Diet Microbiome Poor Health
??
178 seniors
Community
Residential care
![Page 20: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/20.jpg)
If gut microbial dysbiosis is the causeof the disease, then
Fixing the dysbiosis should cure the disease
![Page 21: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/21.jpg)
IBD patients have dysbiosis
![Page 22: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/22.jpg)
What about replacing gut microbes by fecalmicrobial transplantation (FMT)?
• Instillation of gut microbiota from ahealthy person into a sick person
• FMT delivered by colonoscopy,nasogastric tube, or pills
– Colonoscopy
• 300-500 ml
– NG/NJ tube• 60 ml
– Pills• 20-40/dose
![Page 23: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/23.jpg)
FMT does cure C. difficile colitis - clearinfectious cause of disease
• Trial terminated earlybecause it wasdeemed unethical tocontinue antibiotictreatment
![Page 24: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/24.jpg)
![Page 25: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/25.jpg)
2 RCT using FMT to treat UC
GroupTotal N
(active/placebo)
Dutch48 (23/25)
McMaster75 (38/37)
Patient population Mild-mod UC Mild-mod UC
Active arm (realFMT)
500 cc nasoduodenal infusion(120 g donor stool) at wk 0 and3
50 cc enema (8g donor stool)weekly X6
Control Sham FMT (patient stool) Water
OutcomesPrimary Remission (SCCAI < 2 + and
> 1 point reduction in MayoRemission (Mayo score < 3and Mayo endo score=0) @wk 7
Primary outcome 7/23 (30%) vs 5/25 (20%)p=0.51
9/38 (24%) vs 2/37 (5%)p=0.03
*Both trials were stopped early by DSMB due to futility
Moayyedi et al Gastroenterology 2015 April 7Rossen et al. Gastroenterology 2015 March 30
![Page 26: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/26.jpg)
Results are generally not maintained in IBDpatients
This suggests that the “dysbiosis” in IBDpatients is a consequence, not the cause
![Page 27: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/27.jpg)
Intestinal inflammation enhances thegrowth of certain facultative
anaerobes while decreasing thegrowth of obligate anaerobes
Intestinal Inflammation InducesDysbiosis
![Page 28: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/28.jpg)
R3-N+-O-
(TMAO)
R2-SO(Sulfoxide)
R2-S(Sulfide)
R3-NH(Trimethyl Amine)
O2-
H2O2
HOCl
NO3-
(nitrate)
SO4-2
(Sulfate)
Intestinal Inflammation
ONOO-
MucolyticBacteria NOCHO
MucolyticBacteria
Inflammation Provides a Selective GrowthAdvantage for Disease-Producing Pathobionts
![Page 29: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/29.jpg)
Increased oxidative stress protection pathways● increased cysteine and GSH transport
● increased riboflavin and sulfur metabolism● increased pentose phosphate shunt pathway
Increased sulfate transport and metabolism
Increase in amino acid transport
Increase in auxotrophy
Decrease in short chain fatty acids and metabolism
Decreased in amino acid biosynthesis
from Morgan et. al., 2012; Kostic et. al. 2014
Alterations in Microbial Function in IBD
![Page 30: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/30.jpg)
AnaerobicRespiration
ClostridiaBacteriodia
Enterobacteriaceae
CHO
Products of Inflammation Feed the Expansion ofColitogenic Pathobionts
Modified from Winter et. al. EMBO, 2013
![Page 31: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/31.jpg)
Microbiome science needs a healthy dose ofskepticism….
• Do microbiome studies showcausation or just correlation?
• Are changes in microbialcomposition biologically relevant?
• Could anything else explain theresults?
Hanage WP (2014) Nature 512:247-8
![Page 32: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/32.jpg)
What do changes in composition anddiversity really tell us?
![Page 33: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/33.jpg)
There are many species of bacteria, but only somehave adapted to life within us
• Over 50 known bacterial phyla
• Generally only 6 phyla found in gut• Bacteroidetes*
• Firmicutes*• Actinobacteria• Proteobacteria
• Verrucomicrobria• Fusobacteria
Tree of life
• 10-100 trillion organisms• >1000 different species• Bacteria, fungi, viruses
![Page 34: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/34.jpg)
![Page 35: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/35.jpg)
The Phylum Level
![Page 36: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/36.jpg)
Bacteria are very different genetically from oneanother
Bacteriodes fragilis Escherichia coli
Shared genes = 40%
Caenorhabditis elegans(nematode)
Human
Shared genes = 38%
![Page 37: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/37.jpg)
What do changes in ratios at the phylumlevel really mean?
Carlotta De Filippo et al. PNAS 2010;107:14691-14696
![Page 38: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/38.jpg)
Microbiome science needs a healthy dose ofskepticism….
• Do microbiome studies showcausation or just correlation?
• Are changes in microbial compositionbiologically relevant?
• Could anything else explain theresults?
Hanage WP (2014) Nature 512:247-8
![Page 39: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/39.jpg)
Technical andcontamination issues
are rampant in themicrobiome literature
![Page 40: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/40.jpg)
Dilution of starting material increases contaminationeffects
• Sequencing results from a pure cultured sample• Increasing dilution = increased contamination• 3 different sites = 3 different results
Salter et al. BMC Biology 2014:12:87
![Page 41: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/41.jpg)
Contamination is kit dependent
Salter et al. BMC Biology 2014:12:87
![Page 42: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/42.jpg)
Analysis of nasopharyngeal samples from children inThailand as a function of age (Birth-2 yrs of age)
Samples cluster byage
No, samples clusterby extraction kit
Re-extractedNo clustering
Salter et al. BMC Biology 2014:12:87 Turner et al. Plos One 2012:7:e38271
![Page 43: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/43.jpg)
Challenges with microbiome studies
• Problems with human studies
– Confounded by age, geographic locations, lifestyles,diets, host genetics
– Lack of standardization (sampling, extraction,processing, sequencing, analyzing)
– Batch effects – technical challenges
![Page 44: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/44.jpg)
Human Microbiome
![Page 45: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/45.jpg)
GOINGFORWARD
![Page 46: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/46.jpg)
Specificity
Ecosystem Effects
Olle Nature Biotechnology 31(4):309. 2013
![Page 47: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/47.jpg)
BUGS IN THE NEWS
![Page 48: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/48.jpg)
Review ArticleAssociation between Faecalibacterium prausnitziiReduction and Inflammatory Bowel Disease: A Meta-Analysisand Systematic Review of the LiteratureYuan Cao, Jun Shen, and Zhi Hua RanRenji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease,Shanghai Inflammatory Bowel Disease Research Center, Shanghai 200127, China
Gastroenterol Res Pract. 2014;2014:872725.
Faecalibacterium prausnitzii
![Page 49: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/49.jpg)
LETTER doi:10.1038/nature13828
Precision microbiome reconstitution restores bileacid mediated resistance to Clostridium difficileCharlie G. Buffie1,2, Vanni Bucci3,4, Richard R. Stein3, Peter T. McKenney1,2, Lilan Ling2, Asia Gobourne2, Daniel No2, Hui Liu5,Melissa Kinnebrew1,2, Agnes Viale6, Eric Littmann2, Marcel R. M. van den Brink7,8, Robert R. Jenq7, Ying Taur1,2, Chris Sander3,Justin R. Cross5, Nora C. Toussaint2,3, Joao B. Xavier2,3 & Eric G. Pamer1,2,8
• “Identify a “probiotic” candidate that cancorrect a clinically relevant microbiome
deficiency”
• Clostridium scindens, a bile acid 7α-dehydroxylatingintestinal microbe, increases resistance to infection
Nature 2015 Jan 8;517(7533):205-8
Clostridium sp and C. difficile colitis
![Page 50: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/50.jpg)
Akkermansia muciniphila and obesity
• A. muciniphila is a normal commensal thatdigests mucus
• Obese people (and fat mice) and those withtype 2 diabetes have much lower levels
• Mice on a high fat diet had less A. muciniphilaand when the levels were restored the micelost weight, had reduced insulin resistance,and reduced metabolic disorders
• Could A. muciniphila be used as a “probiotic”to treat diabetes or help people lose weight?
Everard et al. Proc Natl Acad Sci USA 2013;;110;220:9066
![Page 51: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/51.jpg)
BUGS AND THE BRAIN
![Page 52: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/52.jpg)
My bacteria made me do it…
•Microbes in the gut canalter brain function andbehaviour– Norepinephrine
– Vagus nerve stimulation
– Release of activebiomolecules
![Page 53: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/53.jpg)
Concepts and Questions
• How to identify effector strains within a microbiome thatare responsible for shaping human biology?
• Majority of resident strains are acquired during the first 3years of life
• Once acquired, majority of strains are retained in anindividual for decades
• Effect of a strains residency may take decades tomanifest
![Page 54: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/54.jpg)
![Page 55: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/55.jpg)
Study designs for identifying microbes that modulatecomplex disease risk – Case Control Studies
Jeremiah J. Faith et al. PNAS 2015;112:633-640
![Page 56: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/56.jpg)
Study designs for identifying microbes that modulatecomplex disease risk – Familial Disease
Jeremiah J. Faith et al. PNAS 2015;112:633-640
![Page 57: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/57.jpg)
Geographic Disease Cluster
Jeremiah J. Faith et al. PNAS 2015;112:633-640
![Page 58: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/58.jpg)
Conclusions
• The gut microbiota is dominated by only a few bacterialphyla but great strain-diversity
• Difficulty in identifying causative strains for complexdiseases as most strains are also found in healthyindividuals
• Complex diseases are more likely to reflect thecontributions of multiple microbial strains that both mediateand mitigate pathogenesis in the context of a specific hostgenotype
![Page 59: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/59.jpg)
The End
![Page 60: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/60.jpg)
Multiple stable compositional states in the developing gutmicrobiota of the premature infant.
Morowitz M J et al. PNAS 2011;108:1128-1133
![Page 61: Is the microbiome really an important player in … · Is the microbiome really an important player in human disease? Karen Madsen, PhD University of Alberta. ... Succession of microbes](https://reader030.fdocuments.net/reader030/viewer/2022013015/5b901f8109d3f2b01e8d841a/html5/thumbnails/61.jpg)
Back in 1917
Clark Stanley, the“Rattlesnake King” in
1917