Anna Karenina and the microbiome
Looking for similarities in perturbed microbiomes may lead us to miss something important
“All happy families are alike; each unhappy family is unhappy in its own way.”
This is the profound opening line from Leo Tolstoy's book Anna Karenina which has been used as a model in disciplines as diverse as business and biology.
Tolstoy is saying that happy, or in other words successful families do everything right. There are many components that contribute to happiness and success and in order be successful, a family must have every component. If one of these components is missing then the family cannot be happy or successful, this gives a large number of ways for a family to be unhappy, but only one for them to be truly happy. Therefore happy and successful families look alike, where as unhappy families fail in numerous ways.
This principle has been used to model success in many different field such as business, psychology, economics and biology. Biology of course is where we become interested and it's easy to see how this principal can bee applied. Successful and well functioning biological systems are all the same because they have all the components working correctly. Failing and poorly functioning systems will look very different because they only need to fail at one point in a very long chain to stop functioning.
In a perspective piece for Nature Microbiology, Rebecca Vega Thurber says that we should consider this lesson from Anna Karenina when thinking about the microbiome. She argues that there is plenty of evidence in the scientific literature showing that patterns exist consistent with the Anna Karenina Principle however, there is a high probability that many have been missed. Vega Thurber's suggestion is carry out extensive time-series experiments combined with stochastic modeling to determine if Anna Karenina can be found hiding in different microbiomes.
While Rebecca Vega Thurber claims that reductionist experimentation have lead to many studies missing Anna Karenina effects, some have claimed that the Anna Karenina hypothesis is also reductionist and over simplistic. A cursory glance of the gut microbiome literature will refute the claim that all healthy microbiomes are the same. Similarly, dysbiosis in the microbiomes of patients with bacterial vaginosis show some significant similarites, corroborated by multiple studies.
Should the quote be “All happy families are happy in their own way; each unhappy family is unhappy in its own way"?
I'm not sure about that. The Anna Karenina hypothesis holds true and is very useful in specific instances, such as in Vega Thurber's study of corals. It is also a very useful hypothesis for moving the microbiome field away from looking for the same trends in all dysbiotic microbiome samples. However, caution must be used when applying this hypothesis, there are enough examples where it simply doesn't fit.
Stress and stability: applying the Anna Karenina principle to animal microbiomes
All animals studied to date are associated with symbiotic communities of microorganisms. These animal microbiotas often play important roles in normal physiological function and susceptibility to disease; predicting their responses to perturbation represents an essential challenge for microbiology. Most studies of microbiome dynamics test for patterns in which perturbation shifts animal microbiomes from a healthy to a dysbiotic stable state. Here, we consider a complementary alternative: that the microbiological changes induced by many perturbations are stochastic, and therefore lead to transitions from stable to unstable community states. The result is an ‘Anna Karenina principle’ for animal microbiomes, in which dysbiotic individuals vary more in microbial community composition than healthy individuals—paralleling Leo Tolstoy's dictum that “all happy families look alike; each unhappy family is unhappy in its own way”. We argue that Anna Karenina effects are a common and important response of animal microbiomes to stressors that reduce the ability of the host or its microbiome to regulate community composition. Patterns consistent with Anna Karenina effects have been found in systems ranging from the surface of threatened corals exposed to above-average temperatures, to the lungs of patients suffering from HIV/AIDs. However, despite their apparent ubiquity, these patterns are easily missed or discarded by some common workflows, and therefore probably underreported. Now that a substantial body of research has established the existence of these patterns in diverse systems, rigorous testing, intensive time-series datasets and improved stochastic modelling will help to explore their importance for topics ranging from personalized medicine to theories of the evolution of host–microorganism symbioses.
2017. Zaneveld, Jesse R. McMinds, Ryan, Vega Thurber, Rebecca. Stress and stability: applying the Anna Karenina principle to animal microbiomes. Nature Microbiology. 10.1038/nmicrobiol.2017.121