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Research Reveals Key Role of Small RNA in Intestinal Colonization

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The intestinal microbiome, an intricate ecosystem teeming with diverse bacterial species, thrives on mutual coexistence. This balance relies on the ability of various bacteria to occupy distinct niches and interact with one another.

However, certain bacteria are disproportionately implicated in specific health conditions. One such bacterium is Segatella copri, which, despite its prevalence, remains underexplored. Led by Prof. Till Strowig at the Helmholtz Center for Infection Research (HZI), a research team has embarked on a quest to investigate the mechanisms behind Segatella copri’s adaptations. Their focus is on understanding how this bacterium responds to environmental signals and the implications of its colonization.

Understanding Segatella’s Dominance

The gut microbiome is not static; it varies significantly across regions globally. For instance, individuals in developed countries showcase different bacterial compositions compared to those in emerging economies. Furthermore, the microbiome can differ markedly among individuals, impacting the types and concentrations of bacterial species present.

Despite these variations, certain bacteria establish dominant roles in specific environments. Segatella copri is a prominent player in one of three recognized enterotypes, especially in developing regions.

Research on Segatella copri is surprisingly limited given its wide distribution. What is known is its proficiency in metabolizing dietary fiber, yet its health implications—whether beneficial or detrimental—remain largely unanswered. While extensive data exists on the microbiome, the precise role of this bacterium has yet to be elucidated.

Determining the health implications of Segatella copri is a primary objective of Prof. Strowig’s study. Although culturing this bacterium in a laboratory setting is challenging, the research team has achieved success.

“Our goal was to identify the conditions that lead to increased colonization of Segatella copri and to discern the cellular processes involved. A deeper understanding of the bacteria’s operations is essential,” explained Strowig. The findings are detailed in a recent publication in Cell Host & Microbe.

The Role of RNA in Bacterial Behavior

The genetic blueprint for all biological functions, including those of bacteria, is inscribed in their DNA. The process involves complex metabolic pathways that require the transcription of genes. By examining the transcriptome—the complete set of RNA molecules within a cell at any given moment—researchers can identify active genes.

“In our analysis of Segatella copri’s transcriptome, we discovered a small RNA that is crucial for the bacterium’s reproduction and spread,” noted Dr. Youssef El-Mouali, the lead author of the study.

This small RNA, termed SrcF (Segatella RNA colonization factor), plays a significant role during the bacterium’s colonization process. Through experiments with mice exhibiting a defined gut microbiome, the researchers demonstrated SrcF’s involvement in the bacterium’s expansion into new territories. Small RNAs are recognized as vital regulators of cellular processes in various organisms, underscoring their importance.

Inter-Bacterial Communication

The team investigated when SrcF is expressed in the cells, hypothesizing that the bacterium’s growth depends on its nutrient availability. High levels of dietary fiber, which serve as an energy source for Segatella copri, are believed to boost its proliferation and enable it to colonize new environments.

The researchers discovered that the presence of certain complex carbohydrates stimulates the production of SrcF, while elevated levels of fructans—sugars primarily derived from fruit—can inhibit SrcF’s activity.

Additionally, it was found that the composition of the gut microbiome influences the activation of the signaling pathway mediated by SrcF. The diverse bacterial species coexisting within the gut engage in competition for nutrients and maintain communication necessary for ecosystem balance.

This equilibrium within the microbiome remains surprisingly stable, often reverting to a healthy state following disturbances. “Our findings indicate that the breakdown of significant amounts of fructans can reshape the interactions among intestinal bacteria,” said Strowig. “We plan to extend our research in this area, contributing to a more profound understanding of the gut microbiome that may eventually benefit human health.”

More information: Youssef El Mouali et al, The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization, Cell Host & Microbe (2024). DOI: 10.1016/j.chom.2024.09.008

Source
phys.org

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