Alternative stable states inhuman intestinal ecosystem

Leo Lahti, Jarkko Salojärvi, Anne Salonen, Marten Scheffer, Willem M de VosISME15 (Aug 30, 2014)

Twitter & Github: @antagomir

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

Atlas of Human Intestinal Microbiota:

>1,000 Western adults

130gen

us-lik

egroups

1,006 Western adult subjects

Human Intestinal Tract(HIT) Chip: High ResolutionPhylogenetic Microarray

Rajilic­Stojanovic et al. Environ Microbiol 2009Rajilic–Stojanovic et al. Gastroenterology 2011

Blue: Low abundanceRed: High abundance

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

Quantifying bi­modality with Potential analysis

CRAN: earlywarnings

Livina et al. 2011; Scheffer et al. 2012

Lahti et al. Nat. Comm. 5:4344, 2014

Stable attractors in theabundance landscape andmicrobiota composition?

78 subjects~3 months

Dialister spp.

Lahti et al. Nat. Comm. 5:4344, 2014

Bim

odalityscore

(%)

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

Confirming bi­stability with temporal analysis

State transitions show larger shifts­> alternative attractors divided by a critical tipping point ?

Bi­stability and the overall ecosystem: varying scales ?

PCA +Correlation (Spearman)

Only Prevotella statesare visible at ecosystemlevel (high ~10%relative abundance;other bi-stable taxa<2% relativeabundance)

Lahti et al. Nat. Comm. 5:4344, 2014

Low (blue) and High (red)abundance Prevotellasubjects highlighted:

Lahti et al. Nat. Comm. 5:4344, 2014

'Tipping elements' of the intestinal microbiota ?

Uncorrelated state switches -> various combinations !

-> Ecosystem states asspecific combinationsof bi-stable taxa?

http://commons.wikimedia.org/wiki/File:RF­remote­control­dip­switch­calculator.png

Ageing and bi­stability: Uncultured Clostridiales I

Lahti et al. Nat. Comm. 5:4344, 2014

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

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 + metadataIn Dryad: http://dx.doi.org/10.5061/dryad.pk75d

Code: CRAN: earlywarningsGithub: microbiome.github.com

Slides: SlideShare

Twitter & Github: @antagomir

#ISME15

Thank You!

Anne SalonenJarkko Salojärvi

Willem M de VosMarten Scheffer HITChip team

#ISME15