Diversity and Stability analysis of the Human Gut Microbiota from Birth to Retirement

The recent discovery of the enterotypes, three distinct clusters of microbial communitycomposition across human population, suggests the existence of alternative stablestates in the gut ecosystem (Arumugam et al. 2011). Alternative stable states ofphylotype composition ­ and transitions between these states ­ may also arise in adynamic manner following changes in health status or life style. We have investigatedthe effect of ageing on the stability landscapes of the intestinal microbiota based onpotential analysis (Livina et al. (2010); Hirota et al. (2011)), a novel approach formodeling microbial and other ecosystems and their evolution across phenotypic andenvironmental conditions. The analysis assumes that the observations follow anunderlying stochastic system with the potential function:

where U(z) is the potential function of the state variable z (here microbial abundance).The latter term presents standard noise from Wiener process. The model describes thepotential states of the system with respect to a continuous indicator variable t (hereageing). The corresponding Fokker­Planck equation connects the potential to theprobability density p of the state variable, providing an approximation for thepotential:

Multiple local minima in the potential landscape indicate the existence of alternativestable attractors of microbial abundance. In the illustrated example, Bacteroidesvulgatus et rel. has two stable attractors with low and high abundance, respectively,which are encountered only in elderly population. The 130 distinct genus­levelphylotypes show various stability patterns with respect to ageing ­ a detailed stabilityanalysis of the HITChip data collection will help to characterize the overall variabilityof the gut ecosystem in terms of other phenotypic and environmental variables,together with the implications of this variation for health and well­being.

Diversity and stability analysis of the human gut

microbiota from birth to retirementLeo Lahti (1), Jarkko Salojärvi (2), Anne Salonen (2), Egbert van Nes (3), Marten Scheffer (3), Willem M. De Vos (1,2)

(1) Wageningen University, Laboratory of Microbiology, Netherlands (2) University of Helsinki, Department of Veterinary Bioscience, Finland (3) Aquatic Ecology and Water QualityManagement group, Wageningen University, Netherlands

The densely populated intestinal microbial ecosystem has a profound impact on our well­being, playing a central role in key bodily functions suchas digestion and immune system. The intestinal microbiota carries a gene pool that exceeds 150­fold the size of our own genome and is highlyvariable in space and time. Characterizing the overall diversity and health associations of this virtual metabolic organ forms a major challenge forcontemporary human biology. Recent accumulation of high­throughput profiling data is now opening novel opportunities to characterizemicrobial diversity in the gut. The phylogenetic Human Intestinal Tract Chip (HITChip; Rajlic­Stojanovic et al. 2009) provides a sensitive,standardized, and highly reproducible analysis platform to assess relative phylotype abundance across phenotypic and environmental conditions.The HITChip array has been designed to target hypervariable 16S rRNA regions of >1000 microbial species­like phylotypes, which present themajority of the so far detected phylotypes of the human intestine. The sensitivity provided by the HITChip microarray is comparable to 200,000NGS runs per sample (Claesson et al. 2009), allowing standardized collection of commensurable high­throughput data sets suited for large­scalemeta­analysis. The platform has been to date applied in a hundred individual studies, accumulating a database of 10 000 microarray experimentsfrom fecal samples of thousands of individuals from over 10 countries. The versatile metadata of the subjects and considerable sample sizeprovide a unique resource for investigatig the overall diversity of the gut ecosystem. Here, we analyse selected subsets of the HITChip datacollection to characterize the evolution of diversity and stability of the intestinal microbiota across human life span from birth to very old age.

LL has been supported by the Finnish Alfred Cordelin foundation and the Academy of Finland (decision 256950).

The species richness in the gut increasesrapidly during the first years of life.

ReferencesArumugam et al. Enterotypes of the human gut microbiome. Nature 473:174­80, 2011.Hirota et al. Global Resilience of Tropical Forest and Savanna to Critical Transitions. Science 334:232­235, 2011.Livina et al. Potential analysis reveals changing number of climate states during the last 60 kyr. Clim. Past 5:2223­2237, 2010.Rajilić­Stojanović M. et al. Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in theabundant microbiota of young and elderly adults. Environ Microbiol 7:1736­51, 2009.

The principal components highlightremarkable differences in phylotypecomposition between children and adultpopulations.

The 1033 species­like and mostly unculturablephylotypes quantified by the HITChip come from23 higher­level taxonomic group (order andphyla), most notably Bacteroidetes and Firmicutes.

Ageing and phylotype diversity in human gastrointestinal tract

Stability of the gut microbiota across life span

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