Outlining 'environmental' view of microbiome awaits craftier study designs, experts say

By Hank Schultz

- Last updated on GMT

Craftier study designs could outline environmental view of microbiome

Related tags microbiome Clinical trials

A more holistic, environmental view of the human gut microbiome is taking shape among researchers, but confounding factors complicate the task of fully elucidating this via tenable study designs.

In the early days of the study of probiotics, individual microbes were identified and studied.  This approach makes perfect sense from the standpoint of being something that can be fit in a study design—one organism and limited goals, such as how well that organism colonizes in the gut or how profoundly it affects a certainly endpoint, such as, say, traveller’s diarrhea.  And of course, that kind of work yields a science suite that can be used to market an ingredient.

Vast complexity of gut

But as inexpensive high throughput next generation genetic sequencing became available, it became possible to quickly identify hundreds of different microbes within the gut.  The full complexity of the microbiome became apparent. And it became apparent, too, that relying on reductionist studies of individual organisms, while important and helpful in their way, was akin to trying to understand the all of interactions of the many species of plants and animals on the Serengeti by observing an individual zebra.

Studies among populations, such as the work Jeff Leach, PhD of the Human Food Project is doing among the Hadza people in Tanzania, have shown that the environment where people live can play a huge role in what their gut makeup looks like.  That kind of information has started to seep into the thinking of researchers across the spectrum of gut health studies, said Robert Hutkins, PhD,  who holds the Khem Shahani Professor of Food Science chair at the University of Nebraska Lincoln. That university recently inaugurated its Nebraska Food for Health Center, which will look at the interplay of food and the microbiome.

Environmental outlook

In the past that was the view, that we were not thinking so much about the bigger picture,” ​Hutkins told NutraIngredients-USA. That is changing now.  Many of us in the field are taking a more ecological view about how best to use probiotics in the diet to promote health. We are considering the environment in which people are living.

In Tanzania Leach has been collecting samples of the microbiomes of many of the Hadza people, a group which to some degree is still living a traditional hunter gatherer lifestyle.  While his work is still ongoing, so far Leach has found that the Hadza microbiome is more diverse than what is typical for people living in industrialized countries and their guts tend to be more resilient.  In other words, it’s harder to push the guts of these people away from their baseline condition via temporary changes to the diet.

Leach’s tentative conclusion, which he relayed during a session at NutraIngredients-USA’s Probiota Americas event earlier this summer in San Francisco, is that the microbiome diversity and resilience he observed in these people has to do with the rich donor environment of microbes where they live.  The Hadza come into contact with and consume many different kinds of plants and animals, none of which are prepared for consumption with Western modes of sanitation and food safety in mind. And they eat, relatively speaking, a huge amount of dietary fiber in the form of raw plant stuffs casually harvested from the environment. The result, Leach said, is a constant stream of new immigrant microbes taking up residence in their guts and plenty of food for those organisms to feed upon.

None of this is exactly new, Hutkins said.  It has been known for a while that the guts of people who grew up on farms look different that urban dwellers. It has also been shown that the guts of people who own pets that venture outside look different from those of pet less apartment dwellers.  Could living in such a meager microbial environment be one of the root causes of the inflammatory, ‘lifestyle’ conditions so common in industrialized countries?

Irish rugby study

A study in 2014 that found that Irish rugby players have more diverse guts than non athletes.  When viewed from an environmental standpoint, a question that could be raised about this study is this: Is this greater diversity a result of the changes the rigors of heavy exercise induce in the gut?  Or is it because these athletes play a grubby, full contact sport and are getting dirt and the sweat, saliva and skin cells of other competitors into their mouths?

Leach said from his experience sequencing the guts of people living a ‘grubby’ life in Tanzania that the latter is certainly possible.  And he said there is some precedent for gut changes with participation in a contact sport.

They found that roller derby women swapped microbes during the duration of a single match,​ he said.  But trying to parse that out via a tenable study design would be quite the trick.There are a dizzying amount of confounders,​ Leach said.

It's my belief that exercise and corresponding sports nutrition does not only train the muscular system, but actually our microbiota adjusts to that stimulus, too. The group of Irish rugby players had for example high levels of ​Akkermansia, which has been linked in past studies to a decreased risk for obesity and systemic inflammation. Strenuous exercise increases inflammation.  Athletes seem to have higher levels of strains with anti-inflammatory properties. They have more strains that are more metabolically active, matching the hostsactivity level,’”​ said Ralf Jäger PhD, principal in the Milwaukee, WI-based consultancy Increnovo LLC.

Controlling for confounding factors

Hutkins said this environmental understanding is advancing across the board, but pinning it down via studies that are affordable is still very difficult.  Could one look at a high activity group, such as forest firefighters, one whose activity level approaches that of athletes? Then the same group could be looked at when they’re ‘clean’ as opposed to when they’re ‘dirty.’  But those confounding factors still encroach. Being covered in dust and soot aren’t the only changes they undergo when they’re out in the wilderness fighting a fire.

These are also professions that have a lot of stress, and they can go either without sleep or eating.  It would be very difficult to set up research like that,​Hutkins said.  But he said that as the field develops, and as more and more researchers try to fit those factors into study designs, more solutions will be found.

As we get more sophisticated in this research we are finding ways to control for those things,” ​he said.

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