Chinese scientists have discovered a new way to know how hosts and gut bacteria interact, potentially opening doors for more precise treatments for diseases linked to imbalances in the gut's microbial environment.
The findings suggest that instead of simply tolerating the vast array of microbes in the gut, the host actively shapes this community, maintaining a dynamic equilibrium.
Experts note that trillions of microorganisms reside in the human gut, playing critical roles in digestion and the development of the immune system. These microbes release various molecules that interact with the host, influencing the growth and function of immune cells.
An imbalance in the gut microbiome, known as dysbiosis, is increasingly linked to various health problems, including obesity, diabetes, fatty liver disease and neurodegenerative disorders, according to medical professionals.
A key question in the field has been whether hosts can specifically recognize and manage particular bacteria within the complex microbial community.
Using advanced proteomics technologies, research teams from the Shanghai Institute of Nutrition and Health at the Chinese Academy of Sciences and the CAS Center for Excellence in Molecular Cell Science discovered that epithelial cells in the mouse gut secrete a "smart identifier" protein called APOL9.
Through an innovative technique combining flow cytometry and microbiome sequencing, the researchers found that this protein can precisely identify a class of bacteria called Bacteroidales. APOL9 scans the bacteria's cell membranes for specific lipid "tags", similar to a barcode reader, enabling selective identification.
"We found a similar process happens to the human homolog APOL2 proteins," said Qian Youcun, a researcher from the Shanghai Institute of Nutrition and Health, CAS.
APOL9 then triggers the targeted bacteria to release "information capsules" known as outer membrane vesicles, or OMVs, to communicate with the host.
Dendritic cells capture these OMVs, activating an immune response that enhances the expression of the "alert system" molecule MHC-II and promotes the development of specific immune cells. This process boosts the gut's defense against harmful bacteria.
A paper detailing the 11-year research effort was published on Wednesday on the website of the journal Nature.
"Such discoveries challenge our traditional understanding of gut microbiota management, highlighting that the body not only maintains balance through broad-spectrum antimicrobial mechanisms, but also possesses the ability for 'targeted communication.' APOL9 acts as a well-trained 'bacterial diplomat,' establishing refined cooperation with specific bacteria to help maintain gut immune homeostasis," said Qian, who is also a co-corresponding author of the paper.
Qian stated that future research will focus on further exploring the function of the human APOL2 protein and how regulating this pathway can strengthen the gut's immune barrier.
"This research is expected to lead to a range of innovative therapies, such as designing medicines to induce specific bacteria to release OMVs and developing intelligent probiotics carrying special lipid 'tags'," he said.
Jiang Changtao, a professor at the School of Basic Medical Sciences, Peking University, noted that the conserved function of human APOL2 suggests this mechanism may be relevant across species, laying a foundation for translational medical research.
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