Understanding the factors that shape microbiomes

In two scientific articles recently published in high-impact journals – Nature Microbiology and Nature Communications – the Systems Ecology group at the University of Luxembourg’s Luxembourg Centre for Systems Biomedicine (LCSB) led by Prof. Paul Wilmes studied the dynamics of microbial communities (microbiomes) over several microbial generations. Their results provide a better understanding of the microorganisms that live in biological wastewater treatment plants, with potential impact on the performance of one of the most widely used biotechnological process on our planet. Using this model system, their work also offers new insights into the many factors, both abiotic and biotic, that shape microbiomes. The fundamental knowledge acquired during these studies will help to predict dynamics and ultimately control microbial communities of interest, including the human microbiome.

The roles of viruses, plasmids and CRISPR-immunity

The dynamics of microbiomes – such as those found in a biological wastewater treatment plants – are driven by both environmental and biological factors. Among the biological factors are bacteriophages and plasmids: invasive mobile genetic elements (iMGEs) which move between organisms and can transfer detrimental or beneficial genetic material to their hosts.

The researchers of the University of Luxembourg studied the impact of viruses (bacteriophages) and plasmids on a model microbial community in a wastewater treatment plant by collecting samples over one and a half years. They especially focused on one bacterial immune system: a defence mechanism used by microorganisms against invasion by iMGEs. Through this so-called CRISPR-Cas system (nowadays widely used as a genetic engineering tool), bacteria can recognise foreign elements and integrate parts of the mobile genetic material into their own genomes. The integrated sequences serve as a genetic memory bank and can be used to interfere with future invasions. By elucidating the CRISPR-mediated interactions between the microorganisms and both bacteriophages and plasmids, the scientists were able to understand better how the structure of the microbial community is shaped by these iMGEs.

The Nature Microbiolog showed that plasmids are highly abundant within the community and have a strong impact on its dynamics. The results suggest that plasmids are the main target of the CRISPR systems, allowing bacteria to selectively retain potentially beneficial genetic material, for example antimicrobial resistance genes. “This is entirely new as it was previously thought that the viruses were targeted predominantly,” explains Susana Martínez Arbas, PhD student at the LCSB and first author of the paper. “It is an important finding as these interactions play a key role in promoting adaptation and diversity within microbiomes. The dynamics are also essential to understand the spread of antimicrobial resistance genes which are typically encoded by plasmids.”y

Understanding the factors impacting microbial populations is crucial as it can help to both devise measures against deleterious species and predict how the community will evolve over time. Based on the researcher’s observations, iMGEs and CRISPR-based interactions should now be taken into account as their incorporation can provide more comprehensive models of community dynamics. “This can of course be used to improve the performance of wastewater treatment plants, but it could also be key in maintaining a healthy gut microbiome for example,” concludes Susana Martínez Arbas.

Microbiomes’ responses to perturbations

To allow long-term stable operation of biotechnological processes such as wastewater treatment plants or to maintain the balance of the human microbiome, it is also important to understand how microbial ecosystems respond to disturbances. This was at the heart of the Nature Communications. The researchers specifically studied resistance and resilience within the microbial community, especially focusing on lipid-accumulating populations as these bacteria have a competitive advantage in fluctuating environments and have compelling potential to be used in circular economic models.

First, they identified all the ecological niches present in the wastewater treatment plant ecosystem (a niche is the match of a species to a specific environmental condition). Then they showed how, under constant conditions, the complementarity of the microorganisms occupying these different niches, as well as the interspecific competition for certain resources, guarantees the stability of the ecosystem and thus of the biotechnological process.

Their results also highlighted that in case of perturbation, such as a change in the availability of nutrients, the composition of the community shifts temporarily: some microorganisms are able to quickly adapt to variations in the environment by adopting specific strategies. For example, one microbial species exhibits extensive plasticity in gene expression, meaning that a set of genes within a species can produce more than one phenotype when exposed to different conditions. The ability to adjust their phenotype – the sum of the organism traits – allows the population to be resistant to fluctuations.

“Globally, the study shows that this microbiome’s resistance and resilience – its capacity to recover after a disturbance – are a function of phenotypic plasticity and niche complementarity,” describes Dr Malte Herold, first author of the article and former PhD student within the Systems Ecology group. “Even though a biological wastewater treatment plant is a controlled process, some factors fluctuate. It has an impact on microbial dynamics and then on the process’ efficiency. So, our results are particularly relevant for the development of future ecological engineering efforts and to achieve our linked sustainability goals,” Dr Herold points out.

Harnessing integrated meta-omics…

On top of providing new insights into the works of microbial ecosystems, the two publications also highlight the potential of integrated meta-omics approaches to study microbiomes. In both studies, they allowed the researchers to identify ecological niches, characterise microbial activity, track gene expression and get an in-depth understanding of the interactions that shape the community’s structure.

“These articles showcase the expertise acquired by the Systems Ecology group over the years. Our team is now developing new methods in this emerging field, with applications far beyond wastewater treatment,” emphasises Prof. Paul Wilmes. “These two studies set the scene for many new exciting applications, including in the context of engineering the human microbiome.”

… and interdisciplinary collaboration within the university

These studies have been possible thanks to University of Luxembourg collaborations coordinated by the Systems Ecology group at the LCSB and the Department of Life Sciences and Medicine (DLSM) of the Faculty of Science, Technology and Medicine (FSTM). “Our group is delighted to form an interdisciplinary bridge between the LCSB, DLSM and FSTM”, underlines Prof. Paul Wilmes.