Beyond diversity: Research links functional microbial signatures with obesity

Human gut microbiota diversity
Most proposed methods of defining a healthy microbiome are based on taxonomic composition. However, this strategy might prove less effective in obesity, according to new research. (Getty Images/Hiroshi Watanabe)

A new functional microbiota index has shown promise for identifying gut bacteria signatures that may be linked to obesity.

Developed by scientists at research institutes from Warsaw and Krakow in Poland, the Gut Microbiome Obesity Index successfully identified subtle functional difference in gut microbiota which were visible even at lower grades of obesity.

The tool differs from other indexes such as the Gut Microbiome Health Index and The Gut Microbiome Wellness Index which use a taxonomy-based approach, offering a new method that harnesses the functional characteristics of the gut microbiome.

“We proved that a single microbial index can be used to distinguish between healthy and obese microbiota and that function-based indices are more useful for this task than taxonomy-based indices,” the authors wrote in Nutrients.

Study details

While a number of studies suggest that the gut microbiome may play a causative role in obesity, it is still unclear exactly which microbiome changes may impact the development of this condition.

Results from clinical trials to date have produced inconsistent results when it comes to associations between the diversity of gut microbiota and obesity, with some studies showing that low alpha diversity is associated with obesity, and some showing the opposite.

The researchers therefore set out to assess metagenomics data from stool samples and create a new method of analysis, using both taxa and functional pathways to correlate which bacterial abundances are associated with BMI.

To do this, they enrolled 305 participants including 109 obese patients, 87 healthy control individuals and 109 esports players. Although the esports players had a normal BMI, they served as another reference group representing individuals with a sedentary lifestyle and a Western diet.

DNA was then isolated from fecal samples and analyzed using whole-genome shotgun metagenomic sequencing to identify bacterial patterns across the groups.

The functional role of gut bacteria

The results revealed that alpha diversity was significantly higher in the obese group compared to the control and esports groups.

Given that this runs contrary to some obesity-microbiota studies, the researchers then divided the participants into obesity groups, ranging from participants with a BMI of 25 kg/m2 to those with a BMI of 50 kg/m2. They then found that only the highest obesity group had significantly higher diversity than normal-weight controls.

When examining which bacteria species were particularly abundant or depleted, no significant taxonomic differences were observed between the control groups and individuals with lower levels of obesity. However, significant differences emerged in those with higher levels of obesity, with 28 bacterial species found to be overrepresented in these individuals.

The researchers then began looking at the functional role of bacteria, comparing specific biological pathways between the groups. The functional index not only differentiated between individuals with extreme obesity and healthy controls but also among those with lower grades of obesity.

“This suggests that subtle functional differences might be visible even at lower grades of obesity before they become more pronounced as BMI increases,” the authors wrote.

How generalizable are the findings?

While the study has its limitations, including a significant gender imbalance within the esports group, the researchers say the findings highlight the importance of evaluating the functional role of the gut microbiota, rather than only considering the species.

“[The findings] indicate that function-based indices are more robust in distinguishing between healthy and dysbiotic states of microbiota, especially if they are not caused by factors such as infection or associated with gastrointestinal symptoms,” they wrote.

“By contrast, no differences were observed between overweight participants and healthy controls, which potentially indicates that no permanent changes occur in the microbiome with weight gain.”

However, they warn that the index may be unique to the Polish population studied and not generalizable to other regions given that gut microbiome composition can vary significantly based on geographic regions.

“To improve the generalizability of the ‘gut microbiome obesity index’, it might be necessary to develop separate indices for different populations or geographical regions rather than relying on a single index,” they wrote.


Source: Nutrients. doi: 10.3390/nu17142320. “The Gut Microbiome Obesity Index: A New Analytical Tool in the Metagenomics Workflow for the Evaluation of Gut Dysbiosis in Obese Humans”. Authors: M. Kulecka, et al.