Is the gut microbiome an important cause of obesity?

Gut Check looks at health claims made by studies, newsmakers, or conventional wisdom. We ask: Should you believe this?

The claim:

Contrary to the hype and even the conclusions of many small studies, microbes inhabiting the human digestive tract — the gut microbiome — are not responsible for obesity except in a trivial way.

Tell me more:

The very first study reporting a link between the gut microbiome and obesity found that lab mice bred for obesity had half as many bacteria belonging to the Bacteroidetes phylum as lean mice did, and lots of bacteria in the Firmicutes phylum.

It had the effect of a starter’s gun at a race: Scientists at labs around the world were off in pursuit of microbes causing obesity. The most intriguing support for that idea: transferring microbes from the guts of normal-weight mice into the guts of obese ones, and obese mice’s gut microbes into slim ones, seemed to cause the animals to switch to the body type consistent with their new bacteria, not their old selves, found a 2004 study.

But those scientists didn’t find the simple dichotomy in humans that they had found in lab mice, suggesting that the ups and downs of bacteria populations followed weight loss rather than causing such loss. Other studies that claimed to find a microbiome/obesity connection had only a few dozen participants.

Two 2014 analyses were the first to seriously challenge the “my gut bugs made me fat” idea. One, led by microbiome pioneer Rob Knight, now at the University of California, San Diego, concluded that the gut microbiomes supposedly associated with obesity “are not consistent between studies even when the data are analyzed with consistent methods.” Another found that the differences between studies in what they found about “fat” or “lean” gut microbiomes were greater by far than the differences between slim and obese individuals within studies. And that tantalizing Bacteroidetes/Firmicutes ratio (high = lean; low = obese) was sometimes true and sometimes not.

When it comes to which kind of microbiome equals slim and which goes along with obesity, “you don’t really see a consistent pattern” in microbiome characteristics such as how many types of bacteria and how many of each type there are, said microbiologist Patrick Schloss of the University of Michigan Medical School, who led a new critique of human obesity/microbiome research.

Really?

Schloss wondered whether the 2014 analyses that seemed to burst the microbiome balloon were missing a true effect. Maybe the individual studies they scrutinized were individually too small to find an effect. He and his postdoctoral fellow, Marc Sze, therefore, gathered up the 10 best studies they could find on the human microbiome, more than anyone had analyzed together.

Their conclusion: Neither the Bacteroidetes/Firmicutes ratio nor the abundance of Firmicutes (also linked to obesity) were “significantly associated with obesity in any study,” Schloss said. Similarly, putting together the largest data sets on people’s BMI and their gut microbiome, there was only limited support for the idea that changes in the microbiome are linked to obesity — which throws cold water on the claims of some dietary supplement makers that probiotics and other ways to change the microbiome could be the route to a Kate Moss body.

A key test of the microbiome-weight link is whether you can correctly classify people as obese or not, based on their microbiome. The accuracy of that, Schloss found, was between 33 percent and 65 percent. “It’s a pretty poor predictor of whether people are obese,” Schloss said. “It’s only a little better than flipping a coin.” Although obese men and women do have less diverse gut microbiomes than non-obese ones, the effect size is so small that “it’s not biologically significant,” Schloss said: If the microbiome makes any difference to your BMI, it’s a tiny one.

Why don’t the results in mice apply to people? For one thing, lab mice are genetically identical, while people are genetically diverse. For another, the reason the mice are obese is their double serving of an obesity gene, whereas the reasons we humans weigh too much are as numerous as the options on a Cheesecake Factory menu. Maybe the microbiome has important effects only when everything else about creatures — mice or people — is identical.

The verdict:

Simplistic claims that the microbiome has an important effect on human obesity are at best exaggerated and at worst wrong.