Over the past decade, researchers have begun to appreciate the importance of a two-way communication that occurs between microbes in the gastrointestinal tract and the brain, known as the gut-brain axis. These “conversations” can change the way these organs work and involve a complex network of chemical signals derived from microbes and the brain that are difficult for scientists to decouple to gain an understanding.
“Currently, it is difficult to determine which microbial species drive specific brain alterations in a living organism,” said first author Dr. Thomas D. Horvath, instructor of pathology and immunology at Baylor College of Medicine and Texas Children’s Hospital. “Here we present an invaluable tool for investigating the connections between gut microbes and the brain. Our laboratory protocol allows for the identification and comprehensive evaluation of metabolites – the compounds produced by microbes – at the cellular level and throughout the animal”.
The gastrointestinal tract hosts a rich and diverse community of beneficial microorganisms known collectively as the gut microbiota. In addition to their role in maintaining the intestinal environment, gut microbes are increasingly being recognized for their influence on other distant organs, including the brain.
“Gut microbes can communicate with the brain through several pathways, for example by producing metabolites, such as short-chain fatty acids and peptidoglycans, neurotransmitters, such as gamma-aminobutyric acid and histamine, and compounds that modulate the immune system such as others,” said co-first author Dr. Melinda A. Engevik, assistant professor of cellular and regenerative medicine at the Medical University of South Carolina.
The role microbes play in central nervous system health is evidenced by links between the gut microbiome and anxiety, obesity, autism, schizophrenia, Parkinson’s disease, and Alzheimer’s disease.
“Animal models have been instrumental in linking microbes to these fundamental neural processes,” said co-author Dr. Jennifer K. Spinler, assistant professor of pathology and immunology at Baylor and Texas Children’s Hospital Microbiome Center. “The current study protocol allows researchers to take steps to unravel the specific involvement of the gut-brain axis in these conditions, as well as its role in health.”
A road map to understand the complex system of trafficking in the gut-brain axis
One strategy researchers used to gain insights into how a single type of microbe might affect the gut and brain was to first grow the microbes in the lab, harvest the metabolites they produced, and analyze them using mass spectrometry and metabolomics. Mass spectrometry is a laboratory technique that can be used to identify unknown compounds by determining their molecular weight and to quantify known compounds. Metabolomics is a technique for the large-scale study of metabolites.
“The effect of the metabolites was then studied in the mini-gut, a laboratory model of human intestinal cells that retains the properties of the small intestine and is physiologically active,” Engevik said. “Furthermore, the microbe’s metabolites can be studied in live animals.”
“We can expand our study to a community of microbes,” Spinler said. “In this way we investigate how microbial communities work together, synergize and influence the host. This protocol provides researchers with a road map to understanding the complex system of trafficking between the gut and the brain and its effects.”
“We were able to create this protocol thanks to large interdisciplinary collaborations involving clinicians, behavioral scientists, microbiologists, molecular biology scientists, and metabolomics experts,” Horvath said. “We hope our approach will help create communities of designer beneficial microbes that can contribute to the maintenance of a healthy body. Our protocol also offers a way to identify potential solutions when miscommunication between the gut and the brain leads to disease “.
Read all the details of this job in Protocols Nature.
Other contributors to this work included Sigmund J. Haidacher, Berkley Luck, Wenly Ruan, Faith Ihekweazu, Meghna Bajaj, Kathleen M. Hoch, Numan Oezguen, James Versalovic and Anthony M. Haag. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospital and Alcorn State University.
This study was supported by an NIH grant K01 K12319501 and Global Probiotic Council 2019-19319, grants from the National Institute of Diabetes and Digestive and Kidney Diseases (Grant P30-DK-56338 to Texas Medical Center Digestive Disease Center, Gastrointestinal Experimental Model Systems) , NIH U01CA170930 grant and unlimited research support from BioGaia AB (Stockholm, Sweden).