New hypothesis: ‘All healthy microbiomes are similar; each dysbiotic microbiome is dysbiotic in its own way’

When Leo Tolstoy wrote the first line of his classic novel Anna Karenina—“All happy families are like one another; each unhappy family is unhappy in its own way”—he probably never thought it would apply to gut microbiomes.

But researchers from University of Washington (USA) and Oregon State University (USA) recently put forward the “Anna Karenina principle” as a way of explaining what might happen when microbial communities in many different environments are subject to perturbation: random variation may occur in microbiota community composition—and compared to baseline, the microbiota may become more varied and unstable.

“Anna Karenina effects”, as the authors call them, could be commonly observed when a host is confronted with a stressor that reduces its ability to regulate microbiota composition; furthermore, these effects are often associated with a decline in host health. So while microbiomes of healthy hosts may all look similar, microbiomes of unhealthy hosts may end up looking very different from one another.

In a Perspective published in Nature Microbiology, Jesse Zaneveld, Ryan McMinds, and Rebecca Vega Thurber cite evidence for Anna Karenina effects in diverse systems, from the microbiome of corals to that of the human upper respiratory tract. When it comes to the authors’ own work on corals, they found stressors including overfishing and nutrient pollution may allow random changes to occur in the coral surface microbiome, allowing algal competitors to flourish and ultimately reducing the growth of corals or killing them altogether.

Zaneveld, et al. write: “Rather than shift the microbiome to a new discrete configuration, producing clusters, these stressors allow the microbiomes of stressed individuals to take on a wider range of possible configurations than healthy controls, producing a constrained ‘core’ of control microbiomes surrounded by a large ‘halo’ or ‘smear’ of stressed or diseased microbiomes.”

Applied to the gut microbiota, the principle may lend unique interpretations to previous studies and provide a useful framework for interpreting future studies. To wit: what would it mean for research on gut microbiota if every dysbiosis were slightly different?

Numerous studies have linked ulcerative colitis with gut microbiota composition, for example, with identification of species that are depleted or enriched in the disease state; however, so far a specific biomarker has not been identified. If the Anna Karenina principle indeed applies in this disease state, scientists may never find a stable dysbiosis associated with ulcerative colitis. Random gut microbiota changes in response to disease-related factors could mean many different configurations are associated with the disease state, and therefore, identification of a highly sensitive and specific gut microbial biomarker of disease may prove difficult. Also, interventions aimed at modulating the gut microbiome in ulcerative colitis in a specific way would be met with varying success.

Many more possible examples of the Anna Karenina principle exist in the body of literature linking gut microbiota dysbiosis to disease. And in the authors’ discussion of examples related to the human gut microbiota, they emphasize the importance of immunity—evidence suggests disruption of normal immune function in a host can destabilize the gut microbiome and possibly induce random variation. The article details the greater microbiome variability seen in individuals positive for human immunodeficiency virus (HIV), who have severely disrupted immunity.

“Predicting when and how normal regulation of microbiomes breaks down is at the heart of many important problems in microbial ecology,” the authors write. More specifically, predicting this is essential in knowing how to modulate the gut microbial ecosystem for better health. On the path toward personalized medicine, the Anna Karenina principle could give scientists new direction for finding biologically meaningful effects of gut microbiota alterations.

 

Reference:

Zaneveld JR, McMinds R, & Thurber RV. Stress and stability: applying the Anna Karenina principle to animal microbiomes. Nature Microbiology. 2017; 2. doi:10.1038/nmicrobiol.2017.121

Kristina Campbell
Kristina Campbell
Science writer Kristina Campbell (M.Sc.), from British Columbia (Canada), specializes in communicating about the gut microbiota, digestive health, and nutrition. Author of the best selling Well-Fed Microbiome Cookbook, her freelance work has appeared in publications around the world. Kristina joined the Gut Microbiota for Health publishing team in 2014.  Find her on: GoogleTwitter