What does a healthy microbiome look like?
In the last decade, the potential for the human microbiome to improve human health has leaped from obscure scientific abstracts onto the public radar. School teachers, health coaches, and dental hygienists and nutrition experts are preaching the need for a healthy microbiome. But what does a healthy microbiome look like?
A Healthy Microbiome is Diverse
Most health professionals will acknowledge the importance of diversity. A microbiome made up of one or two species simply cannot perform all the metabolic tasks necessary to support good health.
Early microbiome studies supported the hypothesis that more diverse microbiomes were associated with healthier people. Clinical implications were that a diverse diet, particularly one rich in complex whole foods, would support a diverse microbiome. Diets rich in simple sugars, starches, and chemical preservatives appear to diminish microbial diversity in the gut. So do antibiotics and other pharmaceuticals that impact microbial communities. This rationale for whole foods and reduced exposure to chemicals lay the foundation for our online course, Managing Your Microbiome*, which remains popular today.
The Microbiome is not Just a Bunch of Bacteria
A frustration many ecologists had with early studies of the microbiome was the focus on bacterial components alone. The abundance of bacteria in the human microbiome led to a biased emphasis on the bacteria present in the human gut. Organisms that were not bacteria, such as fungi or archaea, were largely ignored. So were the microbial communities present in tissues beyond the gut.
New research is confirming what we long suspected-namely that the human microbiome encompasses all tissues and all domains of life. Today, scientists are studying the microbiome on skin, the dental microbiome, and even the brain microbiome. Increasingly they are finding that each microbiome contains non-bacterial species. Prokaryotic archaea and eukaryotic organisms like fungi play underexplored roles in the human microbiome. Viruses, which are not living organisms, are also abundant in the microbiome.
As the species composition data from microbiomes accumulates, the need to identify which species are important for good health has prompted lengthy scientific discussions. Probiotic sales reps will be quick to explain why their strain of Lactobacillus is most important for your health, but data supporting their claims is weakened by the evidence that the microbiome is hyper diverse, and requires many kinds of so-called probiotics.
The truth emerging from these studies is that microbiomes are highly variable, and highly personal. The strains that help one individual may do little to assist another. Therefore the debate about which strains are best cannot be resolved without a deeper understanding of how microbial ecosystems function within the human body.
Functional Diversity May Trump Genetic Diversity
This need for functional data has lead recent microbiome research efforts to focus on the metatranscriptome-the array of mRNA messages that are expressed by the microbiome as a whole. Since many different species of microbes share genes that express similar functions, these studies have suggested that a functional core1 of metabolic activities may be more predictive of good health than a specific mix of species.
To better understand this functional core, it helps to think about labor functions in a large urban center. In cities around the world, many people from diverse backgrounds (aka genotypes) co-exist. Ideally, this coexistence is peaceful. But in terms of the overall health of the city, what really matters is not what genotype dominates the population, but rather how well the water, sewer, trash removal, electrical, communications, and other essential systems function.
Housekeeping Activities Make up the Functional Core
Just as building and maintenance activities (construction, electrical repairs, cleaning, etc.) are priorities for ensuring that a city functions efficiently, so-called cellular housekeeping activities are essential for a healthy microbiome.
In their review of how healthy microbiomes are defined in the scientific literature1, Lloyd-Price et. al. recognize housekeeping functions as key to this functional core. In a living cell, housekeeping functions include activities like building cell membranes (construction), ensuring energy transfer (electrical repairs) and removing cellular waste products (cleaning). These and other functions must be active in order for an individual to maintain good health.
When we shift our focus from genetics (who is there?) to function (what jobs are getting done?), DNA becomes less informative as a diagnostic tool. Afterall, you can have many genes present that are inactive. This is why many researchers are migrating away from genetic analysis in favor of more functionally informative metatranscriptome or metabolomic analysis. A metatranscriptome tells you what genes are being transcribed. A metabolome tells you what products are being made from those transcripts.
How Much Should a Microbiome Change Over Time?
Like food webs in a healthy forest, a healthy microbiome is a dynamic system. Its composition will constantly fluctuate. Species present in the forest in the fall may vanish in the winter. In some years, fireflies or toads may be more abundant than usual. Migratory species may only be detected for a few weeks in the spring. Fires may remove trees, and hailstorms may wipe out berry patches. But if the forest is healthy, the migrants, fireflies, toads, trees, and berries will all return. This stable fluctuation is an important indicator of a healthy food web.
In the human body, the composition of the microbiome will also fluctuate. Changes in daily activities, stress levels, and diets are only a few factors that can disrupt the natural flow of the microbiome. Diversity of housekeeping genes and gene transcripts contributes to microbiome stability over time.
When these changes are dramatic enough to wipe out essential functions, like the ability to digest proteins, or the ability to manage oxidative stress, the microbial food web deteriorates, and disease prevails. In human health, dysbiosis (a collapse of the microbiome) has been associated with essentially every chronic disease examined. This is because we derive much of the energy and nutrition that fuels our own health from the microbial food webs within our microbiome.
Exploring Diversity in Your Own Microbiome
Just as genetic DNA testing has become consumer-friendly due to companies like Ancestry.com or 23andMe, analysis of the microbiome has now reached the consumer market. The company Viome*, launched in 2016, provides functional microbiome testing to consumers in the form of their Gut Intelligence Test*. Tests can be carried out alone, or in conjunction with a Health Intelligence Test* that uses a blood sample to analyze the transcriptomes in your blood.
Comparing the blood-derived transcriptome with the microbially rich metatranscriptome of the gut can provide powerful insights into:
-the composition and functional diversity of your microbiome
-the interactions between your gut microbiome and gene expression in your blood
-foods you can eat to improve your microbiome function and your overall health.
As with any new alternative health technology, results from a Viome* analysis should be viewed, not as a magic bullet, but rather as a different lens with which to view your health. Some caution in interpreting microbiome results is warranted simply because the science is new, microbiomes are dynamic, and our understanding of what a healthy microbiome looks like is evolving2.
1. J. Lloyd-Price, G. Abu-Ali, C. Huttenhower, The healthy human microbiome. Genome Medicine 8, 51 (2016).
2. C. Allaband et al., Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Clin Gastroenterol Hepatol 17, 218-230 (2019).
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