Elucidating a Metabolic Signature that Explains Gut-Related Changes in Human Energy Balance

The Challenge: Exploring the Role of the Gut Microbiome in Human Energy Balance

Human energy balance is a crucial factor in maintaining overall health and well-being. It refers to the equilibrium between energy intake (calories consumed), energy expenditure (calories burned through metabolic processes), and energy output (energy excreted through feces and urine from undigested food). Maintaining a healthy energy balance is essential in various aspects of health, including weight management, cardiovascular health, and immune function. The gut microbiome is emerging as a key modulator of human energy balance. Despite this knowledge, studies to date lack a comprehensive quantitative evaluation of the contribution of the gut microbiome to the entire energy balance equation. Insights into modifiable factors in the microbiome might help manage conditions related to energy balance. To help fill this knowledge gap, this study used a multi-omics approach to profile fecal samples and sera from individuals in a metabolic ward. The insights from this study reveal the complex intersection of host-diet-gut microbiome factors that modulate energy balance and possibly human health.

Metabolon’s Insight: Microbiome-Derived Metabolites and the Host’s Energy Balance

The research group used Metabolon’s Short Chain Fatty Acids Targeted Panel to profile fecal and serum samples from individuals on a Western Diet (WD) or a microbiome-enhanced diet (MBD).¹ Using Metabolon’s technology outputs, the researchers were able to establish an improved understanding of the relationship between the gut microbiome and human energy balance.

The Solution: Changes in Energy Balance Can Be Attributed to SCFAs

This research team conducted a controlled feeding study to detect energy balance changes in response to the diet intervention. They used an MBD, a diet designed to feed and modulate the colonic gut microbiome. They found that compared to the WD, the MBD increased daily fecal energy output consisting of undigested food. Therefore, the MBD produced a significant decrease in host metabolizable energy compared to the WD, consequently reducing the energy available to the host.

Next, they evaluated the microbial phenotype associated with host energy balance. 16S rRNA sequencing of the participants’ gut microbiome revealed that the MDB changed the microbiome composition, increasing the abundance of SCFA-producing bacteria. They found that an increase in fecal and serum SCFA content, including acetic acid, propionic acid, and butyric acid paralleled diet-induced changes in microbial composition. Conversely, the WD starved the gut microbes because the host had digested and absorbed more metabolizable energy in the gastrointestinal tract. Changes in the microbiome due to the MBD were accompanied by a modest weight/body composition change and significant changes in the host’s enteroendocrine system.

The Outcome: Harnessing the Power of the Microbiome for Personalized Medicine

This study integrated metabolomics and profiling of the gut microbiome to understand how the gut microbiome modulates energy balance. Metabolon helped elucidate the complex host-diet-microbiome interplay that modulates human energy balance. The research team found that the gut microbiome can serve as a target for personalized medicine. In this case, optimizing SCFA production through diet could promote a favorable energy balance and improve overall health.