Nature Protocols: New tool reveals communication between gut microbes and the brain

Over the past decade, researchers have begun to recognize the importance of two-way communication between the gastrointestinal microbiome and the brain, known as the gut-brain axis
.
These "conversations" can modify the way these organs work and involve a complex network of chemical signals derived from microbes and brains, which is a challenge for scientists in order to gain understanding
.

Dr.
Thomas D.
Horvath, a lecturer in pathology and immunology at Baylor College of Medicine and Texas Children's Hospital, said, "Currently, it is difficult to determine which microbial species drive specific brain changes
in an organism.
Here, we provide a valuable tool to study the connection between the gut microbiome and the
brain.
Our laboratory protocols allow for the identification and comprehensive evaluation of metabolites (microbial-produced compounds)
at the cellular and whole-animal level.
”

The gastrointestinal tract has a rich and diverse community of beneficial microorganisms, collectively known as the intestinal flora
.
In addition to the role of maintaining the gut environment, the effects of gut microbes on other distant organs, including the brain, are increasingly recognized
.

"The gut microbiome can communicate with the brain through several pathways, such as by producing metabolites such as short-chain fatty acids and peptidoglycans, neurotransmitters such as γ-aminobutyric acid and histamine, and regulating the immune system and other compounds," said
co-first author Melinda A.
Engevik, Ph.
D.
, assistant professor of regenerative and cellular medicine at the Medical University of South Carolina.

The links between the gut microbiome and anxiety, obesity, autism, schizophrenia, Parkinson's disease, and Alzheimer's disease highlight the role
microbes play in central nervous system health.

"Animal models play a vital role in linking microbes to these fundamental neural processes," said
Jennifer K.
Spinler, Ph.
D.
, assistant professor of pathology and immunology at Baylor University and the Microbiome Center at Texas Children's Hospital.
"The protocol in the current study allows researchers to take steps to elucidate the specific role of the gut-brain axis in these situations, as well as its role in
health.
"

A roadmap for understanding the complex transportation system of the gut-brain axis

One strategy researchers use to gain insight into how a single type of microbe affects the gut and brain is to first grow microbes in the lab, collect the metabolites they produce, 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 quantifying known compounds
.
Metabolomics is a technique
for studying metabolites on a large scale.

"The effects of metabolites were subsequently studied in the miniature gut, a laboratory model of human intestinal cells that retain the properties of the small intestine and are physiologically active
," Engevik said.
In addition, metabolites of this microorganism can be studied
in living animals.
”

Spinler said: "We can extend the research to the microbial community
.
In this way, we studied how microbial communities work together, work synergistically and influence the host
.
The protocol provides researchers with a roadmap to understand the complex transportation system between the gut and the brain and its implications
.
”

"Thanks to a large-scale interdisciplinary collaboration of clinicians, behavioral scientists, microbiologists, molecular biologists, and metabolomics experts, we were able to create this protocol
," Horvath said.
We hope that our approach will help create a design community of beneficial microorganisms, which may help maintain a healthy body
.
Our protocol also provides a way to identify potential solutions
when a miscommunication between the gut and brain leads to disease.
”

Thomas D.
Horvath, Sigmund J.
Haidacher, Melinda A.
Engevik, Berkley Luck, Wenly Ruan, Faith Ihekweazu, Meghna Bajaj, Kathleen M.
Hoch, Numan Oezguen, Jennifer K.
Spinler, James Versalovic, Anthony M.
Haag.
Interrogation of the mammalian gut– brain axis using LC– MS/MS-based targeted metabolomics with in vitro bacterial and organoid cultures and in vivo gnotobiotic mouse models.
Nature Protocols, 2022