Microbiome research: Small RNA molecules play crucial role in the microbial colonisation of the gut
Focus on the widespread intestinal bacterium Segatella copri
The intestinal microbiome is currently the subject of intensive research, as it is of great importance for human health. Intestinal bacteria play an essential role in the defence against dangerous pathogens, which is one of the reasons why the majority of them are among the good guys. On the other hand, some of our lodgers are more prevalent in specific diseases—for whatever reason. This also applies to the widespread but little-researched bacterium Segatella copri. The research group led by Prof Till Strowig at the Helmholtz Centre for Infection Research (HZI) and the German Center for Infection Research (DZIF) wanted to determine what makes this bacterium tick. How does it adapt to its environment? And what signals does it react to?
The intestinal microbiome is a highly complex ecosystem with thousands of different types of bacteria. Live and let live, that is the motto. Harmonious coexistence is based on the fact that intestinal bacteria occupy different niches and communicate with each other.
When does Segatella gain the upper hand?
The composition of the human gut microbiome is not always the same. There are significant differences between people in different regions of the world; in the western, highly industrialised world, for example, different bacteria predominate than in developing countries. On the other hand, the gut microbiome varies from person to person in terms of the bacterial species represented and their colonisation density. Despite these differences, there are basic patterns of intestinal colonisation in which a particular key bacterium dominates. Segatella copri is the most prominent germ in one of these three so-called enterotypes. This intestinal bacterium is widespread in developing and emerging countries.
Despite its worldwide distribution, little research has been done on Segatella copri to date. What is known is that the bacterium specialises in the breakdown of dietary fibre. However, what role does it play concerning human health needs to be clarified: is it beneficial, or, on the contrary, does it have adverse effects? Despite the wealth of data on the microbiome, studies to date have not provided an answer to this question.
Clarifying the health significance of Segatella copri is one of the goals of the research work of Prof Till Strowig, head of the "Microbial Immune Regulation" department at the HZI and group leader in the DZIF research areas “Community-Acquired Infections at Mucosal Interfaces” and „Healthcare-Associated Infections”. Cultivating Segatella in the laboratory is difficult, but Strowig's team has succeeded. "We wanted to find out under which conditions increased colonisation with Segatella copri occurs and which processes take place in the cells. To do this, we need insights into how these bacteria work," says Till Strowig.
Small snippet with a big impact
The programme for all life processes is encoded in the genes, and this is no different in bacteria than in humans. When Segatella copri multiplies and spreads, complex metabolic processes are set in motion. To do this, the relevant genes have to be transcribed. For this transcription, the genetic information is transcribed from DNA (deoxyribonucleic acid) to RNA (ribonucleic acid). We can determine which genes are currently active by examining the so-called transcriptome. This is the entirety of all transcribed RNA molecules in a cell at any given time. "While studying the transcriptome of Segatella copri, we came across a tiny snippet of RNA that plays an essential role in the reproduction and spread of the bacterium," reports first author Dr Youssef El-Mouali. The small piece of RNA—small RNA, to use the technical term—is significantly involved when Segatella copri breaks new ground. The researchers showed this in mice with a defined gut microbiome. The fact that "small RNAs" act as essential control elements in regulating cellular processes is also known from other living organisms, including humans.
Intestinal bacteria communicate with each other
The researchers named the RNA snippet discovered in Segatella copri SrcF (Segatella RNA colonisation factor) and took a closer look at it. They wanted to clarify the question: When is SrcF expressed in the cells? The assumption is that the multiplication of the bacterium is dependent on the food supply. If there is a high supply of dietary fibre, from which S. copri obtains energy, the bacteria will spread and conquer new habitats. The researchers were able to show that certain complex carbohydrates trigger the formation of SrcF. In contrast, a high concentration of fructans—polysaccharides consisting mainly of fruit sugar (fructose)—suppresses SrcF activity.
The researchers also discovered something else: The microbiome's composition influences whether Segatella copri activates the signalling pathway via SrcF. The many different bacterial species that live in peaceful coexistence in the gut compete for available resources and communicate with each other. This is the only way to explain the balanced state of the microbiome: The individual composition of the intestinal microbiome is surprisingly constant, and even after temporary turbulence, the old balance within this ecosystem is usually restored.
"According to our research results, the breakdown of large amounts of fructans appears to influence communication between different intestinal bacteria," says Till Strowig. “We will continue our research in this direction and hope that the better understanding of the gut microbiome that we want to contribute to will eventually be used specifically with a view to human health.”
Source: Press release of the Helmholtz Centre for Infection Research
