Microbiota: Who’s Hosting Whom?

Posted on | September 16, 2015 | Comments Off on Microbiota: Who’s Hosting Whom?

Mike Magee

If you search under “The Future of Medicine”, you’ll see that the “Microbiome” is getting a great deal of air space these days. In fact, the NIH has committed $173 million to a collaborative dive titled the Human Microbiome Project. And yet, for most of us, it’s a new enough term that we need to continue to remind ourselves just what it means. But medical researchers have already moved beyond universal theories of its’ significance in normal homeostasis and the pathogenesis of inflammation and a wide range of diseases, and are now honing in on the questions that might be answered in formal studies.

But first, the definitions with the help of David Relman in this week’s JAMA:

Microbiota – “The human microbiota is a fundamental component of what it means to be human.” The term refers to the unique and personalized collection of microorganisms that live and thrive in each of us. As Relman explains: “All animals coexist in intimate, dependent relationships with microbes. Humans are no exception. Host-associated microbes, like nearly all others on this planet, form communities in which the overall composition, structure, and function are explained by ecological processes and environmental factors. Evidence of coadaptation and mutual benefit are key features of these symbioses between hosts and their microbial communities, or microbiotas.”

Microbiome – This term refers to the the collection of genes or genetic material that are contained in each of our microbiotas. Our growing ability to rapidly and cost-effectively analyze genetic structure has now allowed investigators to begin to peer into our microbiota and deconstruct the microbiome.

What they are finding raises some pretty serious questions including “Who’s hosting whom?” As Relman explains, “A recent examination of metagenomic sequence data obtained directly from human microbiota samples at 5 body sites identified more than 3000 biosynthetic gene clusters, each predicted to produce a small molecule with biological activity. Oral and gut communities contained more of these gene clusters (roughly 1100 and 600 per site, respectively) than communities at other, less diverse sites (such as skin and urogenital tract). Some of the most common types of predicted small molecules in the human microbiome are ribosomally synthesized and posttranslationally modified peptides—including lantibiotics, bacteriocins, and thiopeptides.”

Translation – our microbiomes are anything but passive. They are remarkably active and integrated with normal metabolism, physiology and pathophysiology. As importantly, their actions and products can be manipulated. This means that they are potential drug targets, which means that profit seeking individuals and corporations are and will continue to invest time and money in figuring out how they do what they do, and how to adjust their actions to favor wellness.

Relman says we already know a fair amount. Benefits include “differentiation of host mucosa, food digestion and nutrition, regulation of metabolism, processing and detoxification of environmental chemicals, development and ongoing regulation of the immune system, and prevention of invasion and growth of pathogens.” Debits? “…disturbance and alterations of the human microbiota… are associated with a wide variety of human diseases, such as chronic periodontitis, inflammatory bowel disease, and antibiotic-associated diarrhea.”

The field itself is beginning to feel a bit like environmental science turned inward. Consider these remarks, “The current surge of interest in this topic reflects in part recent advances in DNA sequencing technology and its use in characterizing the microbial world directly from environmental samples, as well as a renewed appreciation for ecological principles, including the importance of interactions among organisms; the formation, activities, and stability of communities of microbes; and the relationships between communities and their environment.”

This seems to bring a more nuanced appreciation of the old adage, “We are what we eat”. And it also suggests a note of caution (or optimism), as we see here, “Familiarity with an individual’s microbial ecosystem stability landscape might provide an understanding of their vulnerability to destabilizing factors such as antibiotics, as well as the likelihood of restoring their ecosystem to a health-associated state, for example, using a defined personalized synthetic community and complementary set of nutrients.”

So where are we. The experts seem focused on asking the right questions. Here’s Relman’s list:

1. “What are the most effective approaches for measuring human microbial ecosystem beneficial services?”

2. “What are the most important processes and factors that determine human microbiota assembly after birth?”

3. “Do different community assembly trajectories determine health and disease later in life, and if so, how?”

4. “What are the most important determinants of microbiome stability and resilience?”

5. “How can the stability and resilience of health-associated ecosystem states be strengthened?”

6. “How can health-associated ecosystem states be restored?”

5. “How (does) the microbiome…contribute to disease?”

Stay tuned.

For HealthCommentary, I’m Mike Magee.