Association Between BMI-Related Metabolites, Gut Microbiota, and Obesity

A concept image of gut flora
A concept image of gut flora
Metabolites could be mediators in the connection between gut microbiota and obesity and points to potential future opportunities for targeting the gut microbiota in the prevention of obesity.

There may be an association between 3 genera in the Lachnospiraceae family (Blautia, Dorea, and Ruminococcus) and SHA-98 gut microbiota genera and plasma metabolites (glutamate, branched chain amino acids [BCAAs], and BCAA-related metabolites) that are potentially predictive of body mass index (BMI), with a possible metabolite mediator role between gut microbiota and obesity, according to a study published in the Journal of Clinical Endocrinology & Metabolism.

Researchers recruited 920 Swedish individuals, the majority of whom were women (53%), with an average age of 39 years, who were currently participating in the Malmö Offspring Study. Investigators sequenced the gut microbiota of 674 individuals who provided stool samples for analysis.

The purpose of the study was to identify an association between BMI and a specific plasma metabolite profile in the healthy general population, as well as determine whether the identified metabolic profile was in any way associated with a specific composition of gut microbiota.

Study results found that 25 metabolites had significant loadings (P <.05); however, BMI was associated with a total of 19 metabolites (P <.001 for all), with glutamate being the metabolite with the strongest association with BMI (P = 5.2e-53). Other metabolites demonstrating a positive contribution to the BMI predictive model include 8 metabolites related to BCAA metabolism (P <.001 for all), whereas significant negative contributions were associated with serine, asparagine, threonine, and citric acid. Positive associations between principal component predictive of BMI (PCBMI) and cardiometabolic disease-associated traits, such as waist circumference, fasting glucose, low-density lipoprotein cholesterol, triglycerides, and systolic blood pressure, were observed, in addition to the negative association of high-density lipoprotein cholesterol between PCBMI and cardiometabolic disease.

Researchers found a positive association between 3 genera in the Lachnospiraceae (Blautia, Dorea, and Ruminococcus) and PCBMI, whereas SHA-98 and unidentified genera in the Clostridiaceaeo and Rikenellaceae families exhibited a negative correlation. Finally, after adjustments were made for age and sex, there were only positive associations between PCBMI and the Lachnospiracae family, and a significant negative association with SHA-98. When PCBMI was used as a covariate with 4 gut bacteria associated with PCBMI, it was found that none of the bacteria was associated with BMI after adjusting for age, sex, and metabolite PCBMI.

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Researchers concluded that plasma glutamate and BCAA-related metabolites were found to be strongly associated with obesity, and both BMI-related metabolites and BMI were related to gut bacteria from the Lachnospiraceae family (Blautia, Dorea, and Ruminococcus) and SHA-98.

Further, it was determined that gut bacteria contributed to the variation of BMI within the variation of glutamate and BCAA-related metabolites, which strongly suggests that gut bacteria and plasma metabolites are not independent factors, but exist in the same chain of events that lead to obesity, possibly serving as mediators. Clinicians can potentially anticipate research emerging that explores targeting gut microbiota in an effort to prevent obesity.


Ottosson F, Brunkwall L, Ericson U, et al. Connection between BMI related plasma metabolite profile and gut microbiota [published online February 1, 2018]. J Clin Endocrinol Metab. doi: 10.1210/jc.2017-02114