Researchers have discovered that the distribution of microbial communities within the gastrointestinal (GI) tracts of mice is not uniform, affecting immune cell populations.
A team from the Experimental and Clinical Research Center of the Max Delbrück Center and Charité — Universitätsmedizin Berlin (ECRC) has conducted research indicating that various parts of mice’s gastrointestinal tracts contain different types of microbial communities. Furthermore, the particular composition of these microbiota can impact the quantity and variety of immune cells present in specific areas. The findings, published in Gut Microbes, outline the intricate arrangement of immune cells and microbial populations, offering a framework for exploring the relationship between gut microbes and inflammatory conditions.
Past studies have suggested that there are “hotspots” along the GI tract where interactions between certain immune cells and microbes may occur more frequently. However, no comprehensive investigations have taken place across the entire intestinal system, according to Dr. Hendrik Bartolomaeus from the Immune-Microbial Dynamics in Cardiorenal Disease lab led by Dr. Nicola Wilck, and co-author of the research. “Our main motivation was straightforward: How are immune cells arranged throughout the gut, and in what ways does the microbiome affect this arrangement?”
Microbial communities influence the immune system
The researchers contrasted the GI tracts of germ-free mice with those of conventionally colonized mice, segmenting their intestines and extracting microbial DNA. They employed metagenomic sequencing to identify all bacterial species present. Simultaneously, they isolated immune cells from each segment for analysis through flow cytometry, a popular method for recognizing and measuring various immune cell types based on specific markers.
The findings revealed that not only did the composition of microbial communities in the GI tracts of conventional mice change depending on their location, but this also significantly impacted the distribution and types of immune cells present along the gut. For example, adaptive immune cells, which develop after encountering antigens — substances that provoke an immune response — were more prevalent in the lower sections of the intestine, whereas innate immune cells were found in greater numbers in the upper parts. This distribution was drastically altered in germ-free mice, which do not have bacterial antigens in their intestines.
Harithaa Anandakumar, a PhD student and lead author, categorized the immune cells based on whether their presence and quantity were influenced strictly by location, through interaction with the microbiota at that site, or by a combination of both factors. She then developed an app that consolidates this information. “We created a user-friendly app so that anyone interested in a specific type of immune cell can check its abundance in the gut, and see if it’s affected by the microbiome, the location, or by a mix of both.”
This resource was previously unavailable, according to Wilck, also an expert at Charité’s Department of Nephrology and Medical Intensive Care. Now, it serves as a valuable tool for scientists working with mouse models. His lab focuses on how immune cells migrate from the gut to various tissues and organs in different mouse disease models. “This resource enables us to investigate whether the immune cells we observe in organs damaged by hypertension or kidney disease originate from the gut,” he explains.
