Timescales of gut microbiome dynamics

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Vast communities of microorganisms inhabit the gastrointestinal tracts of humans and other animals. Understanding their initial development, fluctuations in composition, stability over long times, and responses to transient perturbations – in other words their dynamics – is important both for gaining basic insights into these ecosystems and for rationally manipulating them for therapeutic ends. Gut microbiome dynamics, however, remain poorly understood. We review here studies of gut microbiome dynamics in the presence and absence of external perturbations, noting especially the long timescales associated with overall stability and the short timescales associated with various underlying biological processes. Integrating these disparate timescales, we suggest, is an important goal for future work and is necessary for developing a predictive understanding of microbiome dynamics.

Introduction

It is nowadays well appreciated that the legions of microbes resident in the gastrointestinal tracts of humans and other animals play major roles in development, health, and disease. Because a wide range of disorders are correlated with differences in gut microbial community composition, intentionally altering the composition of the intestinal flora is a major aim of many research strategies that share the ultimate goal of developing effective therapies. So far, progress toward this end has been quite limited. Treatments such as fecal microbiome transplantation ameliorate Clostridium difficile infection [1], but the underlying mechanisms remain largely mysterious and hard to generalize to other diseases. Similarly, microbiome perturbation using probiotic supplementation or diet changes remains inconsistently effective, hard to predict, and contentious [2,3••].

Understanding how to alter the composition of the gut microbiota requires, almost tautologically, an understanding of how the gut microbiota changes over time. Natural timescales for fluctuations should give a sense of the stability or instability of the microbiome, and timescales for responses to perturbations should inform strategies to maximize or minimize the system’s adoption of new steady-state dynamics. In contrast to characterizations of community membership in different hosts at a given time, however, characterizations within a single host over a range of times are relatively few. Nonetheless, recent studies have provided some sense of the stability and response times of the gut microbiome in humans and other animals. In this review we summarize existing data on the dynamics of vertebrate gut microbiomes, discuss likely mechanisms governing dynamical timescales, and provide suggestions to guide future work.

Section snippets

Stability of the gut microbiota

The considerable majority of experiments on gut microbiomes are cross-sectional in nature, meaning that multiple individuals are sampled at a single timepoint. A handful of longitudinal studies, however, in which data from the same individual are collected and compared over time, reveal a picture of rough stability of the human gut microbiota in adults over timescales of months and years. These studies typically make use of fecal samples, most often analyzed by sequencing 16S ribosomal RNA

Instability of the gut microbiota

Though stable long-term behavior may suggest sluggish dynamics, gut microbial communities can exhibit rapid changes, both autonomously and in response to perturbations. Observations in model animals show major, self-driven changes taking place within less than one day. Thaiss et al. sampled the mouse microbiome every four or six hours, uncovering strong diurnal rhythms in bacterial abundance and localization, as well as in host transcription [27]. In zebrafish, live imaging shows-specific

Determinants of timescales for the gut microbiota

Empirically observed timescales characterize gut microbiome dynamics, ranging from fast responses on the order of days to slow changes on the order of months or years, must somehow be set by the timescales of underlying biological processes that influence the gut and its residents. These processes include microbial growth, intestinal transport, circadian and seasonal rhythms, bacterial evolution and horizontal gene transfer, and colonization and transmission. We will comment on aspects of each

Mathematical and experimental models

The fast timescales associated with responses of gut microbiota to perturbations and the slow timescales associated with overall stability are likely intertwined, together determining the population dynamics of gut microbial communities through means that are largely unknown. Mathematical models have the potential to provide insights into the coupling of timescales. Most dynamical modelling efforts to date, however, have ignored all intrinsic temporal factors other than bacterial growth rates.

Declaration of Competing Interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The authors thank Karen Guillemin and Travis Wiles for useful conversations. This work was supported through an award from the Kavli Microbiome Ideas Challenge, a project led by the American Society for Microbiology in partnership with the American Chemical Society and the American Physical Society and supported by The Kavli Foundation. Work was also supported by the National Institutes of Health (http://www.nih.gov/), under Awards P50GM09891 and P01GM125576-01 to R.P. and T32GM007759 to B.H.S.

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