Model Deepens Understanding of Human Microbiomes

MedicalResearch.com Interview with:
Amir Bashan, PhD, and
Yang-Yu Liu, PhD
Channing Division of Network Medicine
Brigham and Women’s Hospital and Harvard Medical School
Boston, Massachusetts

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We coexist with a vast number of microbes—our microbiota—that live in and on our bodies, and play important roles in human physiology and diseases. Our microbiota is inherently dynamic and changes throughout our lives. The changeability of our microbiota offers opportunities for microbiome-based therapies, e.g. fecal microbiota transplantation (FMT) and probiotic administration, to restore or maintain our healthy microbiota. Yet, our microbiota is also highly personalized and possess unique microbial “fingerprints” in both species assemblages and abundance profiles. This raises fundamental concerns regarding the efficacy and long-term safety of generic microbiome-based therapies. In particular, it is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (i.e. universal) or host-specific.

If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. In this case,
we have to design truly personalized interventions, which need to consider not only the unique microbial state of an individual but also the unique dynamics of the underlying microbial ecosystem. In addition, host-specific microbial dynamics, if they exist, raise a major safety concern for FMT, because although the healthy microbiota are stable in the donor’s gut, they may be shifted to an undesired state in the recipient’s gut. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. We can design general interventions to control the microbial state (in terms of species assemblage and abundance profile) of different individuals.

MedicalResearch.com: What are the main findings?

Response: We develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies— the Human Microbiome Project and the Student Microbiome Project—we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after FMT.

MedicalResearch.com: What should readers take away from your report?

Response: These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We anticipate that applying our method to microbiome data of subjects with other diseases (especially non-gastrointestinal diseases) or infants at different developmental stages will offer deeper insights into how dynamical processes shape human microbial ecosystems. Our method can also be directly applied to other microbial ecosystems—for example, the microbiome of soil, ocean, lakes, phyllosphere/rhizosphere and fermenters—to detect the universality of the underlying ecological dynamics. This sheds light on the design of more advanced methods to extract dynamical information from microbial data.

MedicalResearch.com: Is there anything else you would like to add?

Response: FMT has been very successful in treating patients with recurrent C. difficile infections. Yet, we don’t know why. What we’ve found here – that different people share similar ecological networks associated with the gut microbiome – may help us understand why FMT works. Our work also suggests that we can design very generic microbiome-based therapies to treat patients with disrupted microbiomes. Because we share similar ecological networks, truly individualized or personalized therapies, which consider not only the unique microbial state of an individual but also the unique dynamics of the underlying microbial ecosystem, may not be needed in order to shape the healthy microbiome.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Amir Bashan, Travis E. Gibson, Jonathan Friedman, Vincent J. Carey, Scott T. Weiss, Elizabeth L. Hohmann, Yang-Yu Liu.Universality of human microbial dynamics. Nature, 2016; 534 (7606): 259 DOI: 10.1038/nature18301

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