▎ WuXi AppTec content team editor
More than half of the cells in our bodies are not human cells, but microbes that live in symbiosis with us. Among them, the intestine becomes the most important gathering place for microorganisms. Trillions of communities of bacterial-dominated microbes shape our health here, and imbalances in microbial communities have been shown to be closely linked to a variety of diseases — from gut diseases to metabolic diseases such as diabetes and obesity, and even neurological diseases. The key to linking microbes to multiple diseases is the brain-gut axis.
Image credit: 123RF
There is growing evidence that the host and gut microbiome are interdependent, and that the brain-gut axis that connects the central nervous system to the gastrointestinal tract plays an important role. Compounds released by the microbial community circulate with the blood and regulate physiological functions such as the host's immune response, metabolism and brain function through the brain-intestine axis. However, whether the brain's neurons can directly perceive the composition of bacteria, and whether bacteria can regulate physiological processes by regulating neurons, is still unknown.
In the latest issue of the journal Science, scientists from institutions such as the Institut Pasteur in France reveal a mysterious connection between the brain and gut bacteria. They found in mouse models that hypothalamic neurons can directly detect changes in gut bacterial activity and regulate physiological processes such as appetite and body temperature based on their changes. This finding proves that there is direct communication between gut microbes and brain neurons, or that it may provide new treatment ideas for metabolic disorders such as diabetes and obesity.
The research team focused on the nucleotide oligomerization domain 2 (Nod2) receptor. This pattern recognition receptor is present in the vast majority of immune cells and helps the immune system recognize fragments of the bacterial cell wall — cell wall peptides. Previous studies have found that mutations in genes encoding the Nod2 receptor are associated with metabolic diseases such as Crohn's disease, as well as neurological disorders and mood disorders. However, these studies are not enough to prove that neuronal activity in the brain is directly related to bacterial activity in the gut.
In the latest paper, the research team used brain imaging techniques to observe that neurons in different regions of the mouse brain, especially the hypothalamus, expressed the Nod2 receptor. Further experiments found that when in contact with the cell wall peptides of gut bacteria, the electrical activity of neurons was inhibited.
When Nod2 is specifically knocked out in the hypothalamus's inhibitory γ-aminobutyric acid neurons, these neurons are no longer inhibited by cell wall peptides, and the brain loses control of processes such as food intake and body temperature. The result is that mice (especially older female individuals) gain weight and are more susceptible to type 2 diabetes.
▲Schematic diagram of the mouse experiment of the study (image source: Reference[1])
From this, the study demonstrated that neurons can directly sense the cell wall peptides of bacteria, a process that was previously thought to require the involvement of immune cells. Corresponding author Dr Pierre-Marie Lledo of the Institut Pasteur said: "As a brain center, the hypothalamus is responsible for regulating key processes such as body temperature, fertility, hunger and thirst, and we found that the cell wall peptides of bacteria can act directly on the hypothalamus, which is a surprising discovery. ”
This study shows that neurons can detect bacterial activity, such as reproduction and death, to directly determine the effect of food intake on intestinal balance. Excessive intake of specific foods can stimulate the disproportionate growth of certain bacteria or pathogens, thus jeopardizing the balance of the gut microbiome.
Nod2 of the hypothalamus is involved in regulating body weight and body temperature (Image source: Reference[1])
The effects of cell wall peptides on hypothalamic neurons and metabolism have also raised concerns about their potential impact on other brain functions and are expected to help us understand the association of specific brain diseases with mutations in the Nod2 gene. The discovery also points the way for other interdisciplinary studies in neuroscience, immunology and microbiology, and based on this breakthrough, we can expect that more brain diseases and metabolic disorders may usher in new therapies.
Cover image: 123RF
Resources:
[1] Ilana Gabanyi et al., Bacterial sensing via neuronal Nod2 regulates appetite and body temperature. Science(2022) DOI: 10.1126/science.abj3986
[2] Decoding a direct dialog between the gut microbiota and the brain. Retrieved Apr. 15, 2022 from https://medicalxpress.com/news/2022-04-decoding-dialog-gut-microbiota-brain.html
More recommendations
Click "Watching" and go again