Two dynamic regimes in the human gut microbiome

The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on gut microbial time series has largely focused on autoregressive models (e.g. Lotka-Volterra). However, we show that most of the variance in microbial time series is non-autoregressive. In addition, we show how community state-clustering is flawed when it comes to characterizing within-host dynamics and that more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior suggestive of fixed carrying capacities and abundant taxa were largely shared across individuals. This mean-reverting behavior allowed us to apply sparse vector autoregression (sVAR)—a multivariate method developed for econometrics—to model the autoregressive component of gut community dynamics. We find a strong phylogenetic signal in the non-autoregressive co-variance from our sVAR model residuals, which suggests niche filtering. We show how changes in diet are also non-autoregressive and that Operational Taxonomic Units strongly correlated with dietary variables have much less of an autoregressive component to their variance, which suggests that diet is a major driver of microbial dynamics. Autoregressive variance appears to be driven by multi-day recovery from frequent facultative anaerobe blooms, which may be driven by fluctuations in luminal redox. Overall, we identify two dynamic regimes within the human gut microbiota: one likely driven by external environmental fluctuations, and the other by internal processes.

[1]  Vanni Bucci,et al.  MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses , 2016, Genome Biology.

[2]  Ewa Marta Syczewska,et al.  Empirical power of the Kwiatkowski-Phillips-Schmidt-Shin test , 2010 .

[3]  L. Rigottier-Gois,et al.  Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis , 2013, The ISME Journal.

[4]  Rob Knight,et al.  Longitudinal analysis of microbial interaction between humans and the indoor environment , 2014, Science.

[5]  Peter J. Wangersky,et al.  Lotka-Volterra Population Models , 1978 .

[6]  James M. McCracken,et al.  Convergent cross-mapping and pairwise asymmetric inference. , 2014, Physical review. E, Statistical, nonlinear, and soft matter physics.

[7]  Harry J Flint,et al.  The role of pH in determining the species composition of the human colonic microbiota. , 2009, Environmental microbiology.

[8]  Chris Chatfield,et al.  Introduction to Statistical Time Series. , 1976 .

[9]  Roded Sharan,et al.  Competitive and cooperative metabolic interactions in bacterial communities. , 2011, Nature communications.

[10]  Ashley Shade,et al.  Temporal patterns of rarity provide a more complete view of microbial diversity. , 2015, Trends in microbiology.

[11]  M. Wells,et al.  Variations and Fluctuations of the Number of Individuals in Animal Species living together , 2006 .

[12]  Travis E. Gibson,et al.  Universality of Human Microbial Dynamics , 2016, Nature.

[13]  João Ricardo Sato,et al.  Modeling gene expression regulatory networks with the sparse vector autoregressive model , 2007, BMC Systems Biology.

[14]  Wes McKinney,et al.  Data Structures for Statistical Computing in Python , 2010, SciPy.

[15]  J. Bakken,et al.  Treating Clostridium difficile infection with fecal microbiota transplantation. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[16]  Riccardo Fusaroli,et al.  Inferring Causality from Noisy Time Series Data - A Test of Convergent Cross-Mapping , 2016, COMPLEXIS.

[17]  R. Knight,et al.  Forensic identification using skin bacterial communities , 2010, Proceedings of the National Academy of Sciences.

[18]  J. Clemente,et al.  The Impact of the Gut Microbiota on Human Health: An Integrative View , 2012, Cell.

[19]  C. Granger Some recent development in a concept of causality , 1988 .

[20]  J. Gordon,et al.  IgA response to symbiotic bacteria as a mediator of gut homeostasis. , 2007, Cell host & microbe.

[21]  Eric P. Nawrocki,et al.  An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea , 2011, The ISME Journal.

[22]  G. Michailidis,et al.  Regularized estimation in sparse high-dimensional time series models , 2013, 1311.4175.

[23]  Jonathan Friedman,et al.  Inferring Correlation Networks from Genomic Survey Data , 2012, PLoS Comput. Biol..

[24]  R. Knight,et al.  Moving pictures of the human microbiome , 2011, Genome Biology.

[25]  Gunnar Rätsch,et al.  Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota , 2013, PLoS Comput. Biol..

[26]  Katherine H. Huang,et al.  Identifying personal microbiomes using metagenomic codes , 2015, Proceedings of the National Academy of Sciences.

[27]  Harry J Flint,et al.  The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases , 2012, The ISME Journal.

[28]  Hongzhe Li,et al.  A two-part mixed-effects model for analyzing longitudinal microbiome compositional data , 2016, Bioinform..

[29]  Ferenc Jord,et al.  Network ecology: topological constraints on ecosystem dynamics , 2004 .

[30]  Karoline Faust,et al.  Metagenomics meets time series analysis: unraveling microbial community dynamics. , 2015, Current opinion in microbiology.

[31]  Georg K Gerber,et al.  The dynamic microbiome , 2014, FEBS letters.

[32]  Charles K. Fisher,et al.  Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression , 2014, PloS one.

[33]  Rob Knight,et al.  The Earth Microbiome project: successes and aspirations , 2014, BMC Biology.

[34]  R. E. Carlson,et al.  Monotone Piecewise Cubic Interpolation , 1980 .

[35]  Lawrence A. David,et al.  Diet rapidly and reproducibly alters the human gut microbiome , 2013, Nature.

[36]  Yan Wang,et al.  Predicting microbial interactions by using network-constrained regularization incorporating covariate coefficients and connection signs , 2015, 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM).

[37]  C. Press Cell host & microbe , 2007 .

[38]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[39]  George Sugihara,et al.  Detecting Causality in Complex Ecosystems , 2012, Science.

[40]  Skipper Seabold,et al.  Statsmodels: Econometric and Statistical Modeling with Python , 2010, SciPy.

[41]  Stephen G. Hall,et al.  Vector Autoregressive (VAR) Models and Causality Tests , 2016 .

[42]  J. Clemente,et al.  Human gut microbiome viewed across age and geography , 2012, Nature.

[43]  Eric Jones,et al.  SciPy: Open Source Scientific Tools for Python , 2001 .

[44]  Eric J Alm,et al.  Host lifestyle affects human microbiota on daily timescales , 2014, Genome Biology.

[45]  Ana Freire,et al.  Potential role of the glyoxalase pathway as a drug target in Leishmania infantum: an exact steady-state model analysis , 2007, BMC Systems Biology.

[46]  H. Zou,et al.  Regularization and variable selection via the elastic net , 2005 .

[47]  Harry J Flint,et al.  Interactions and competition within the microbial community of the human colon: links between diet and health. , 2007, Environmental microbiology.

[48]  Antonio Gonzalez,et al.  Subsampled open-reference clustering creates consistent, comprehensive OTU definitions and scales to billions of sequences , 2014, PeerJ.

[49]  P. Bork,et al.  Enterotypes of the human gut microbiome , 2011, Nature.

[50]  William T. Langford,et al.  Biodiversity and species interactions: extending Lotka-Volterra community theory , 2003 .

[51]  R. Knight,et al.  The Human Microbiome Project , 2007, Nature.

[52]  P. Schloss,et al.  Dynamics and associations of microbial community types across the human body , 2014, Nature.

[53]  Christopher E. McKinlay,et al.  Rethinking "enterotypes". , 2014, Cell host & microbe.

[54]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[55]  C. Quince,et al.  Dirichlet Multinomial Mixtures: Generative Models for Microbial Metagenomics , 2012, PloS one.

[56]  Seppo Salminen,et al.  The Mucin Degrader Akkermansia muciniphila Is an Abundant Resident of the Human Intestinal Tract , 2007, Applied and Environmental Microbiology.