A new and powerful tool for revealing the communication between gut microbes and the brain

summary: Researchers develop a new tool that allows studying the connection of microbes in the digestive tract and the brain.

Source: Baylor College of Medicine

In the past decade, researchers have begun to appreciate the importance of the two-way communication that occurs between microbes in the gut and the brain, known as the gut-brain axis.

These “conversations” can modify how these organs function and involve a complex network of chemical signals derived from microbes and the brain that challenge scientists to separate them in order to gain understanding.

The first author, Dr. Thomas D.

“Here we present a valuable tool that enables investigations of the connections between gut microbes and the brain. Our lab protocol allows for the comprehensive identification and evaluation of metabolites—compounds produced by microbes—at the cellular and whole-animal level.”

The digestive system houses a rich and diverse community of beneficial microorganisms collectively known as the gut microbiota. In addition to its role in maintaining the intestinal environment, the gut microbiota is increasingly being recognized for its influence on other distant organs, including the brain.

“Gut microbes can communicate with the brain in several ways, for example by producing metabolites, such as short-chain fatty acids and peptidoglycans, neurotransmitters, such as gamma-aminobutyric acid and histamine, compounds that modulate the immune system and others,” said co-first author Dr. .

The role that microbes play in central nervous system health is highlighted by links between the gut microbiome and anxiety, obesity, autism, schizophrenia, Parkinson’s disease, and Alzheimer’s disease.

Co-author Dr Jennifer K. Spinler, assistant professor of pathology and immunology at Baylor and the Children’s Hospital Microbiome Center of Texas: “Animal models have been paramount in connecting microbes to these essential neuronal processes.”

“The protocol in the current study allows the researchers to take steps toward revealing the specific involvement of the gut-brain axis in these conditions, as well as its role in health.”

A roadmap for understanding the complex traffic system in the gut-brain axis

One strategy researchers have used to gain insight into how one type of microbe affects the gut and brain consists of first cultivating the microbes in the lab, collecting the metabolites they produce and analyzing 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 identify known compounds. Metabolomics is a technique for the large-scale study of metabolites.

“The effect of the metabolites was next studied in small gut, which is an in vitro model of human gut cells that retain properties of the small intestine and are physiologically active,” said Ingvik. “In addition, the microbe’s metabolites can be studied in live animals.”

“We can extend our study to the microbial community,” Spinler said.

In this way we investigate how microbial communities work together, synergize and influence the host. This protocol gives researchers a road map to understanding the complex passage system between the gut and the brain and its effects.”

“We were able to create this protocol thanks to a large multidisciplinary collaboration that includes physicians, behavioral scientists, microbiologists, molecular biologists, and metabolic experts,” said Horvath.

We hope that our approach will help create tailored communities of beneficial microbes that may contribute to maintaining a healthy body. Our protocol also provides a way to identify potential solutions when miscommunication between the gut and the brain leads to disease.”

Read all the details of this work in Nature Protocols.

Other contributors to this work include Sigmund J. Heidacher, Berkeley Luck, Wenley Rowan, Faith Ekoyezu, Meghna Bajaj, Kathleen M. Hoch, Numan Ozgwen, 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.

Funding: This study was supported by NIH grant K01 K12319501 and the World Probiotic Council 2019-19319, grants from the National Institute of Diabetes and Digestive and Kidney Diseases (grant P30-DK-56338 to the Texas Digestive Disease Center, Experimental Gastrointestinal Model Systems), NIH grant U01CA170930 and support My research is unrestricted from BioGaia AB (Stockholm, Sweden).

See also

Around this research news is the brain-gut axis

author: Homa Schalchi
Source: Baylor College of Medicine
Contact: Huma Shalci – Baylor College of Medicine
picture: Image credits to Baylor College of Medicine

Original search: Closed access.
“Interrogation of the mammalian gut axis using LC-MS/MS-based target metabolites with bacterial and organoid cultures in vitro and in vivo murine modelsWritten by Thomas D. Horvath et al. Nature Protocols

Summary

Interrogation of the mammalian gut axis using LC-MS/MS-based target metabolites with bacterial and organoid cultures in vitro and in vivo murine models

Interest in the connection between the gastrointestinal tract and the central nervous system, known as the gut-brain axis, has led to the development of quantitative analysis platforms for analyzing microbe- and host-derived signals.

This protocol enables investigations of the links between microbial colonization and enteric and cerebral neurotransmitters and contains strategies for the comprehensive evaluation of metabolites in in vitro (organoids) and in vivo mouse model systems.

Here we present an enhanced workflow that includes procedures for preparing gut-brain axis model systems: (Phase 1) growth of microbes in defined media; (Phase 2) ICSI of intestinal objects; and (Phase 3) generation of animal models including germ-free (microbe-free), pathogen-free (whole gut microbiota) and pathogen-specific (germ-free mice associated with the whole gut microbiota of a specific pathogen-free mouse). diseases), and Bifidobacterium teeth And Bacteroides ovatus Mono-related mice (germ-free mice colonized with a single gut microbe).

We describe targeted liquid chromatography-metabolomics tandem mass spectrometry-based methods for the analysis of microbially derived short-chain fatty acids and neurotransmitters from these samples.

In contrast to other protocols that typically examine only stool samples, this protocol includes bacterial cultures, organelle cultures, and in vivo samples, in addition to monitoring the metabolite content of stool samples. The incorporation of three experimental models (microbes, organisms, and animals) enhances the impact of this protocol.

The protocol requires 3 weeks of colonization of mice with microbiota and ~1–2 weeks for liquid chromatography–mass spectrometry-based quantitative analysis, sample post-treatment and normalization.