Researchers analyzed human colon samples in a new study to map the interactions between gut bacteria populations and the immune system.
Human bodies are composed of a diverse array of cells forming various tissue types and providing an essential line of defense against possible disease-causing factors such as viruses and “evil” bacteria.
The human body’s main defense mechanism is the immune system, which enlists various types of highly specialized immune cells to keep the body systems “safe” and in good shape, defending them against harmful microbes.
And yet our bodies are also abundant in colonies of bacteria. We may be hosting as many as 38 trillion bacteria at any given time according to some researchers. Such bacteria most often help to maintain our state of health.
In the human body one of the most bacteria-rich areas is the intestine. Recent research has shown that gut bacteria can play a highly complex role within controlling various processes throughout the human body, with specialists even referring to a gut-brain axis.
Why, though, has a “machinery” as responsive as the human immune system allowed below micro-organisms to settle inside our guts? And how do immune cells deal with the bacteria in the gut?
These are some of the questions that the Wellcome Sanger Institute researchers in Hinxton, UK, recently aimed to tackle.
‘The microbiome is critical for health’
“The colon, as a barrier tissue, reflects a special immune environment in which immune cells display tolerance towards a diverse microbial population known collectively as the microbiome.” Senior author Sarah Teichmann, Ph.D., and her colleagues write in their new study paper featured in the journal Nature Immunology.
“The microbiome is important for many health aspects, and a commensal imbalance and pathogenic[ illness-causing] microbes are related to many disease states,” the authors of the study continue to write.
It is important to gain as detailed an understanding as possible of the interactions between gut bacteria and the immune system for these purposes, they demonstrate.
The current study is part of the project Human Cell Atlas, which seeks to provide a detailed reference map of all the cells within the human body.
“[ The report] provides a new understanding of the relationship between immune cells and microbiomas in healthy colon tissue and, by allowing us to specialize in cells in specific areas, it will be a crucial guide for ongoing work on diseases affecting specific colon regions,” says the senior author of the study.
As part of this project, the current research concentrated on mapping the interactions between gut bacteria and immune cells by analyzing postmortem samples from organ donors of healthy human colonists.
The researchers looked at the bacterial communities present in each segment and the immune cells that shared this community using samples from different segments of the human colon.
‘First in-depth map’
The team ended up analysing more than 41,000 immune cells ‘ regulated genes. This allowed them to recognize the genes that were triggered in the various types of immune cells present in each of the segments of the colon.
In addition, the investigators were able to find out which unique bacterial species in each of these parts of the human colon were present, offering new insights into how bacteria and immune cells communicate in the gut.
He observed that the various parts of the colon had different populations of resistant T cells.
Therefore, whereas in the colon’s cecum area— where the large intestine starts— T-helper 17 cells were most abundant, the sigmoid colon— the portion of the large intestine nearest to the rectum— had T-helper 1 cells in abundance.
This result supports prior observations from studies in mice, the researchers note.
The variations in the distribution of immune cells in the colon often balance differences in the distribution of bacterial populations.
One such example is that of the more abundant Bacteroides bacteria in the sigmoid colon, in the vicinity of the T-helper 1 cells.
The researchers demonstrate that current animal studies have shown that by releasing amounts of polysaccharides, certain bacteroids may be directly responsible for the proliferation of that particular set of T-helper cells.
“Our unique approach allowed us to create the first in-depth map of immune cells and their neighboring bacteria in the healthy human colon and revealed that, surprisingly, there are distinct immune niches across the colon, with different cell activation states in different areas.”
– First author Kylie James, Ph.D.
Why the body ‘puts up with’ gut bacteria
But what are those results actually showing? The immune cells they found in the colon are regulatory immune cells, whose function is to decrease the strength of the immune response, according to the study authors.
The new research confirms previous mice work by indicating that these regulatory immune T cells initially migrated to the colon from lymph nodes— which play a key role in directing the immune response.
This step, and the very existence of regulatory immune cells in the colon, the investigators claim, may explain why bacteria can live in the gut without automatic rejection by the immune system.
“We are made up of as many bacteria as human cells and there is a symbiotic relationship between humans and their microbiota,” says co-author of the study Trevor Lawley, Ph.D.
“By exposing the complexity of the microbiome in different colon locations and the interactions with immune cells, we will begin to understand the biology behind this and inform future site-specific gut bacteria research.
