Study shows small RNA plays crucial role in intestinal colonization

The gut microbiome is a very complex ecosystem housing thousands of different types of bacteria. Live and let live, that is the motto. Harmonious coexistence relies on the fact that intestinal bacteria occupy different niches and communicate with each other.

On the other hand, some of our tenants are more affected by specific illnesses, for whatever reason. This also applies to the widespread but little-studied bacterium Segatella copri. The research group led by Professor Till Strowig from the Helmholtz Center for Infection Research (HZI) wanted to find out what drives this bacteria. How does it adapt to its environment? And what signals does it react to?

When does Segatella take over?

The composition of the intestinal microbiome is not always the same. There are significant differences between different regions of the world; in highly industrialized Western countries, for example, bacteria predominate differently than in developing countries. In contrast, the gut microbiome varies from person to person in terms of bacterial species represented and colonization density.

Despite these differences, there are fundamental patterns of intestinal colonization in which a particular key bacterium dominates. Segatella copri is the most important organism in any of these three enterotypes. This intestinal bacteria is widespread in developing and emerging countries.

Despite its global distribution, little research has been conducted on Segatella copri to date. What we do know is that the bacteria specializes in breaking down dietary fiber. However, its role on human health must be clarified: is it beneficial or does it have harmful effects? Despite the wealth of data on the microbiome, studies to date have not provided answers.

Clarifying the importance of Segatella copri for health is one of the aims of a study by Professor Strowig, head of the Department of Microbial Immune Regulation at the HZI. Growing Segatella in the lab is difficult, but Strowig’s team succeeded.

“We wanted to know under what conditions increased colonization by Segatella copri occurs and what processes occur in the cells. To do this, we need to better understand how these bacteria work,” says Strowig. The work is published in the journal Cellular host and microbe.

Small extract with big impact

The program for all life processes is encoded in genes, and this is no different in bacteria than in humans. When Segatella copri multiplies and spreads, complex metabolic processes are triggered: to do this, the relevant genes must be transcribed. For this transcription, genetic information is transcribed from DNA (deoxyribonucleic acid) into RNA (ribonucleic acid). We can determine which genes are currently active by looking at something called the transcriptome. This is the totality of all RNA molecules present in a cell at any given time.

“By 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 bacteria,” reports first author Dr. Youssef El-Mouali.

The little piece of RNA – small RNA, to use the technical term – is significantly involved when Segatella copri innovates. The researchers showed this in mice with a defined gut microbiome. The fact that small RNAs act as essential control elements in the regulation of cellular processes is also known from other living organisms, including humans.

Gut bacteria communicate with each other

The researchers named the RNA extract discovered in Segatella copri SrcF (Segatella RNA colonization factor) and took a closer look at it. They wanted to clarify the question: When is SrcF expressed in cells? The hypothesis is that the multiplication of the bacteria depends on the food supply. If there is a high intake of dietary fiber, from which S. copri obtains its 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 sugars (fructose)) suppresses SrcF activity.

The researchers also discovered something else: the composition of the microbiome influences whether Segatella copri activates the signaling pathway via SrcF. The many different bacterial species that live in peaceful coexistence in the intestine 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 gut microbiome is surprisingly constant, and even after temporary turbulence, the former balance within this ecosystem is usually restored.

“According to our research results, the breakdown of large amounts of fructans seems to influence the communication between different intestinal bacteria,” explains Strowig. “We will continue our research in this direction and hope that the better understanding of the gut microbiome to which we wish to contribute will ultimately be used specifically for human health.”