Exciting Microbe Research? Temper That Giddy Feeling in Your Gut

The following originally appeared on The Upshot (copyright 2017, The New York Times Company).

While we have long known about the existence of microbes — the tiny bacteria, fungi and archaea that live all around, on and in us — our full relationship has become one of the hottest topics for research only in recent years.

Scientists believe that every person contains as many independent microbial cells as human cells. This collection of life, known as the microbiome, provides useful functions for us. Indeed, some of the things we think our bodies do are actually the abilities and enzymes of life-forms living within us. They can help with digestion, vitamin synthesis and even immunological responses.

But, as with many new breakthroughs and advances, the hype of the microbiome often outweighs the reality. This seems especially likely in the field of nutrition. Doing research on the microbiome is not easy, and there are many opportunities to foul things up. To accomplish human studies, large samples of people and microbiomes are needed to account for potential confounding variables.

Specimens have to be collected and stored carefully because contamination has been a big problem. DNA has to be extracted, amplified and sequenced. Finally, powerful bioinformatics tools are necessary to assemble and analyze the huge amount of data contained in a sequence of nucleotides — all of which has resulted in a wide range of new “omics,” including genomics, proteomics, transcriptomics and metabolomics.

Of course, if we think that microbes play a large role in health, we have to rethink the role that antimicrobials play in our lives. In this thinking, antibiotics and antifungals could be life-changing or life-threatening. But that’s not the case. There are many reasons to avoid unnecessary use of these medications, but the microbiome appears able to withstand most treatment.

Still, antimicrobials clearly have an effect on the microbiome. Many studies, along with common sense, suggest that when we treat people with antibiotics, we change the amount and type of microbes that live in our gut. We’ve seen this with Clostridium difficile.

C. diff, as it is also known, is a bacterium that lives in many healthy people. The presence of other microbes keeps its numbers in check. But when we treat people with antibiotics that kill off other bacteria, but not C. diff, it can increase its presence and lead to serious illness. Infection with C. diff is hard to treat, and it’s not uncommon. In 2011 in the United States, there were more than 450,000 cases, causing 29,000 deaths.

A number of studies have shown promise in using the microbiome to treat C. diff. Fecal transplant (which is exactly what it sounds like) effectively fixes a damaged microbiome by infusing it with a healthy one. This type of therapy could theoretically work in treating other diseases.

But there’s a huge gap between “holds promise” and “definitive treatment.” After all, there’s a direct biological explanation for why the microbiome and antibiotics play a role in C. diff. That direct link is much harder to describe when talking about other disorders.

Many have postulated that the microbiome has an important part to play in inflammatory bowel diseases, which, because of my condition, I follow quite closely. Others have attempted to link it to disorders of development and behavior, like autism. Because the microbiome takes root in childhood, studies have explored if pregnancy, method of delivery or even the environment might hold some meaning in the microbiome’s development and later health.

Even more significantly, many have begun to hypothesize that it has a significant role in the current obesity epidemic. Studies have shown that transferring the microbiome from a thin mouse to an obese one, or vice versa, could lead to a change in body size to match. It was this type of study that roused much of your ire when I dismissed it in my discussion of artificial sweeteners. Other studies show that changes in diet can change the microbiome in human beings.

But when you analyze all these studies together, as scientists did in a meta-analysis last summer, the certainty of those links becomes much less certain.

This doesn’t mean that the microbiome doesn’t play a role in nutrition. Some important research has begun to show that chronic malnutrition probably causes changes in the microbiome that make treating the problem much harder than many anticipate. Problems with substandard sanitation can also contribute to microbial changes in very poor environments, compounding the problems of malnutrition. But we haven’t yet figured out how to translate these findings into easily used treatments.

The problem with getting too enthusiastic about the microbiome isn’t much different from the problem with getting too enthusiastic about any research advances. Many mistake correlation for causation; just because some people have a different microbiome doesn’t mean that microbes are responsible for other differences. Studies in mice are not the same as studies of humans; diet is incredibly complex, and rarely do results in genetically similar animals easily translate to diverse groups of people.

And the microbiome is very, very complicated. We understand so little about it, and the idea that we can make accurate representations about it, let alone manipulate it, is somewhat far-fetched.

As with the genome before it, our greater understanding of the microbiome has spurred great excitement and interest. Last May, the White House began the National Microbiome Initiative, with huge public and private investment into research. We hope these investments will yield great returns, but it will be important to temper our enthusiasm with an appropriate amount of skepticism. Health advances usually proceed more slowly than the hype.

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