New research begins to connect the dots between the gut microbiome and health outcomes

A recent study led by Kun Lu, PhD, leader of the UNC SRP’s Project 3, and collaborators, developed a new methodology that could help provide more insights into the role of the gut microbiome, the trillions of microbes in the intestine, in arsenic-induced metabolic disorders such as diabetes.  

Kun Lu

Dr. Kun Lu

This study, recognized by the National Institute of Environmental Health Sciences (NIEHS) as an Extramural Paper of the Month, compared the feces, blood, and brain tissues of mice lacking microbes in their gut, and compared them to mice with normal microbiomes using a new metabolomics methodology that combining targeted and untargeted approaches to identify known and unknown metabolites in the tissues. Their analysis revealed potential links between brain function and the gut microbiota. 

The director of UNC’s SRP, Rebecca Fry, PhD, describes the results from the Lu lab as truly ground-breaking due to the sophisticated approach used to determine the effect of microbes in the gut on the metabolites produced during cell processes.

Rebecca Fry

Dr. Rebecca Fry

She explains, “Their data support inter-organ transport and crosstalk between the gut and the brain. These data are critical for researchers focusing on the microbiome.”  

Extracting these samples and analyzing them using high-resolution mass spectrometry (HRMS) provided insight into the first of its kind high-coverage metabolome characterization on the microbiota-host relationship. Further, the use of a germ-free mouse model in conjunction with the HRMS, alongside a suite of statistics and visualization tools, contributed to the strength of the study, and allowed for a more complete profiling.   

According to the study, activities and signals from the microbiota have associations with mental and neurological disease outcomes like depression, autism spectrum disorder, Alzheimer’s disease, and Parkinson’s disease – but the underpinnings of these connections has been unclear. The methods and models mentioned above moved the research forward in addressing this and provide insight into future connections.  

Lu explains, “By discovering the biochemical landscape regulated by the gut microbiome, this new study expands the horizon and scope of chemical signaling of microbiome-host interactions.”  

Project 3 aims to characterize the largely unknown contributions of the gut microbiome to inorganic arsenic-induced diabetes using new approaches such as this new high coverage metabolomics methodology.