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Could The Gut Microbiome Contribute to Obesity?

If you’re struggling with your weight, you’re not alone. America’s obesity epidemic is at an all-time high. According to a 2016 report from the Centers for Disease Control, 39.8% of American adults are obese. Perhaps even more troubling, 18.5% of youth are considered obese. The CDC defines adults who have a body mass index (BMI) of 25 to 29.9 as overweight, and a BMI of 30 and above as obese.

America’s weight problem doesn’t just take a toll on the individual trying to slim down; it also burdens the health care system, costing almost $250 billion a year. It can also dramatically increases the risk of chronic disease and endangers lives. Obesity can cause heart disease, stroke, and certain types of cancer, which are the leading causes of preventable death.

While healthcare providers continue to search for new ways to help patients control their weight, scientists have been hard at work looking for the root causes of obesity. We do know that the gut microbiome plays a role in eating disorders, so it stands to reason that it may affect obesity. Over the past decade, research on how the human gut microbiome contributes to obesity has yielded mixed results. Studies in mice, however, indicate that the gut microbiome may, in fact, affect obesity. This promising research might just be the key that finally unlocks a door to the prevention of obesity in humans.  

 

The gut microbiota can cause obesity—in mice

Researchers studied mice to determine the long-term effects of environmental changes on the interaction between host genetics, microbiota composition, and metabolic phenotype. Specifically, they looked at three strains of mice specially bred to be obesity-prone or obesity-resistant. The researchers fed high-fat diets to several generations of these mice in an attempt to induce obesity.

When they analyzed the fecal microbiota of the mice, they found that the phenotypes of genetically related mice were different in terms of obesity development but only when the mice were kept in separate facilities. However, when the mice were kept in the same facility for several generations, their phenotypes were similar in terms of the development of obesity. The researchers concluded that, in mice, while the microbiota plays an important role in the development of obesity, genetics and environmental factors interact to contribute to obesity.

The mouse GI tract is similar to that of humans in a few specific ways. For one thing, both species’ gastrointestinal tracts are made up of organs that are anatomically similar to each other. Thus the question arises: can the human microbiota interact with genetics and environmental factors and contribute to obesity in humans?

It’s important to note that despite the similarity that mice’s GI tracts have with that of humans, there are significant differences, too. For example, both species have a cecum—a pouch at the beginning of the large intestine. In humans, this pouch doesn’t have a special function; however, in mice, the cecum is a fermentation chamber where specialized bacteria break down otherwise indigestible plant materials.  The cecum is also proportionally much larger in mice than it is in humans.

There are also microscopic differences between mice and humans’ GI tracts, like a thicker mucosal wall in the human colon, which could change the way the guts of mice and humans host certain kinds of bacteria. There are cellular contrasts, too. Goblet cells and Paneth cells are distributed differently throughout mice and humans’ GI tracts, which researchers in a 2015 study suggest could cause different local immune responses that might shape the composition of the gut microbiota.

Those differences make it hard to generalize about how the microbiome may impact obesity in humans. It’s also much easier to do obesity studies in mice, who can easily be divided into control and experimental groups, fed a simple experimental diet, and put through mazes for exercise. Unless human subjects are kept in a lab and monitored 24/7, it’s impossible for researchers to know if they are following a prescribed eating and exercise plan.

 

Of mice and men (and women!)

While the mouse microbiome interacts with genetics and environmental factors to contribute to the development of obesity, the research in humans is still emerging.

One study found that gastric bypass surgery causes permanent positive changes to the human gut microbiome, helping regulate fat in a healthy way over the long term. Researchers took fecal samples from fourteen women nine years after bariatric surgery and compared them to samples from obese women who hadn’t had the surgery. They found significant differences in the microbiota of the two groups.

Then, they inserted stool from both groups into the guts of mice, colonizing the rodents’ GI tracts with the women’s bacteria. The mice colonized with bacteria from women who had had the operation gained less weight than the other mice. These results suggest that gastric bypass surgery creates changes to the gut microbiome that are still apparent almost a decade later.

This is some of the most promising research yet about the impact of the gut microbiome on obesity. However, a meta-analysis of several studies could not find an association between microbiome profiles and obesity status.

Scientists have also found differences in the fecal protein profiles of obese and non-obese people. One 2015 study characterized the human fecal metaproteome, which can help provide information about how gut bacteria colonization works. The aim of the research was to detect differences at a functional level. The scientists found that the phylum Bacteroidetes was metabolically more active in the obese than non-obese subjects. Their next research challenge is to figure out exactly how.

The field that may most likely help scientists discover how the microbiome impacts body weight is metabolomics, which is the examination of blood and tissue (like that in the GI tract) to find small molecules (metabolites) that may have come from bacteria or organisms outside the human body. Metabolomics has provided insights into how gut microbiota are involved in the development of obesity-related metabolic diseases, including nonalcoholic fatty liver disease. In one metabolomics study from 2016, mice that received intestinal bacteria from mice with high blood glucose (resulting from a high-fat diet) were likely to develop steatosis and insulin resistance. This evidence indicates that gut microbiota are connected to the risk factors for nonalcoholic fatty liver disease, including insulin resistance and inflammation.

If data from metabolomic studies could be used with other types of data from other studies, it might provide a way for scientists to understand exactly how the human microbiome contributes to, or causes, obesity.

In fact, experts in the field of gut microbiota and obesity recommend taking what’s referred to as a systems biology approach. A 2018 review of all the research done so far on the gut microbiome’s impact on obesity suggested that evaluating many different types of data sets can provide greater insight on how the microbiome contributes to obesity. It can also teach us about how other metabolic diseases develop.

 

A contrary view

Research chemist Derek Lowe is skeptical about the connection between the human microbiome and obesity. He critiques the small sizes of many rodent studies and flawed machine learning models that analyze the data. He also expresses concern about the lack of conclusive findings in humans to date. Lowe suggests that obesity signatures may vary more among different people than we yet realize. He also proposes that further research is needed to know if there’s any relation at all between the gut microbiota and obesity in people.

The differing opinions about the role the gut microbiome plays in obesity indicate that it is a particularly challenging field of research. Ethnicity, genetics, diet, and medication interact to impact gut health. That means that analyzing the resulting data is tricky.

 

Moving the science forward

More studies may shed further light on the connection between obesity and the gut microbiome. New microbiome research projects continue to get scientific funding, and federal agencies, including the NIH, received funding increases in 2018. The Microbiome Interagency Working Group coordinates microbiome research across the federal government’s sixteen funding agencies. The group’s interagency strategic plan for microbiome research was published April 19, 2018. The plan describes how much funding each agency has dedicated to microbiome research and explains how the working group plans to dedicate resources to this emerging field.

New information about how obesity develops in people, as well as what the gut microbiome’s connection is to obesity in humans, can ultimately move us toward a greater understanding of how to prevent and treat obesity.

Until scientists have definitive answers, the best strategy for winning your own battle against weight is to eat a healthy diet rich in vegetables, fruits, and whole grains. Not only can it help you feel better, your gut microbiome may be healthier, too.

 

Curious to learn how your microbiome is associated with different gut and lifestyle conditions? SmartGut provides you with a detailed clinical report on how your microorganisms are associated with gut conditions and metabolic disorders, including diabetes, obesity, and non-alcoholic fatty liver disease. Learn more here!