1) The study analyzed data from over 1,000 Western adults and found evidence that some taxa in the human gut microbiome exist in alternative stable states, shifting between high and low abundance profiles. 2) Specifically, around 10% of prevalent taxa showed bimodal abundance distributions and reduced stability at intermediate abundances, indicating bi-stability. 3) These bi-stable "tipping elements" can co-occur in different combinations and have been linked to metabolic syndrome and inflammatory bowel disease.

1. Alternative stable states in
human intestinal ecosystem
Leo Lahti, Jarkko Salojärvi, Anne Salonen, Marten Scheffer, Willem M de Vos
ISME15 (Aug 30, 2014)
Twitter & Github: @antagomir

2. Ecosystem restoration with fecal transplants
- van Nood et al. NEJM 2013
- Fuentes et al. ISME J 2014
Enterotypes of the human gut microbiome
- Arumugam et al. 2011
Mouse & Chimpanzee
- Wu et al. Science 2011
- Moeller et al. Nat. Comm. 2012
- Wang et al. PNAS 2014
Clusters vs. gradients ­methodological
issues:
- Jeffery et al. Nat Rev. Microbiol. 2012;
- Koren et al. PLoS CB 2013
Prevotella bi­modality
- Jeffery et al. Nat. Rev. Microbiol.
Koren et al. PLoS CB 2013

3. Atlas of Human Intestinal Microbiota:
>1,000 Western adults
130 genus-like groups
1,006 Western adult subjects
Human Intestinal Tract
(HIT) Chip: High Resolution
Phylogenetic Microarray
Rajilic­Stojanovic
et al. Environ Microbiol 2009
Rajilic–Stojanovic et al. Gastroenterology 2011
Blue: Low abundance
Red: High abundance

4. Characteristic 'abundance types'
in 1000 western adults:
~% indicates proportion among prevalent taxa
~50% ~20%
~10%
~10% ~10%
Lahti et al. Nat. Comm. 5:4344, 2014

5. Quantifying bi­modality
with Potential analysis
Livina et al. 2011; Scheffer et al. 2012
Dialister spp.
CRAN: earlywarnings
Stable attractors in the
abundance landscape and
microbiota composition?
Lahti et al. Nat. Comm. 5:4344, 2014
78 subjects
~3 months

6. Confirming bi­stability
with temporal analysis
State transitions show larger shifts
­>
alternative attractors divided by a critical tipping point ?
Lahti et al. Nat. Comm. 5:4344, 2014
Bimodality score (%)
N=401
Bi-stable taxa:
Prevotella groups
(oralis & melaninogenica)
Dialister spp.
Uncultured Clostridiales I-II
B. fragilis group
Clostridium groups
(difficile, colinum, sensu stricto)
Uncultured Mollicutes
Lactobacillus plantarum
+ evidence in methanogenic archaea Intemediate stability (r); N=78

7. Bi­stability
and the overall ecosystem: varying scales ?
PCA +
Correlation (Spearman)
Only Prevotella states
are visible at ecosystem
level (high ~10%
relative abundance;
other bi-stable taxa
<2% relative
abundance)
Lahti et al. Nat. Comm. 5:4344, 2014
Low (blue) and High (red)
abundance Prevotella
subjects highlighted:

8. 'Tipping elements' of the intestinal microbiota ?
Uncorrelated state switches -> various combinations !
Lahti et al. Nat. Comm. 5:4344, 2014
-> Ecosystem states as
specific combinations
of bi-stable taxa?
http://commons.wikimedia.org
/wiki/File:RF­remote­control­dip­switch­calculator.
png

9. Ageing and bi­stability:
Uncultured Clostridiales I
Lahti et al. Nat. Comm. 5:4344, 2014

10. Summary
Evidence for alternative stable states in specific taxa:
1) Bimodal log-abundance distributions (~10% of prevalent taxa)
2) Reduced stability at the intermediate abundance range
Bi­stable
tipping elements co­occur
in various combinations
Links to disease ?
- UCI/II: negative association to Obesity/IBS
- High Dialister spp. & B. fragilis & Low Prevotella: MetS
Causality: drivers or passengers?
- Competition & mutualism
- Feed-back loops

11. Bi­stable
tipping elements in human intestinal microbiota
(Lahti et al. Nat. Comm. 5:4344, 2014)
Data: 1,006 western adults x 130 genus-like groups + metadata
In Dryad: http://dx.doi.org/10.5061/dryad.pk75d
Code: CRAN: earlywarnings
Github: microbiome.github.com
Slides: SlideShare
#ISME15
Twitter & Github: @antagomir

12. Thank You!
Jarkko Salojärvi Anne Salonen
#ISME15
Marten Scheffer Willem M de Vos HITChip team