Dear Colleagues,

Genes do not function as single entities but work in concert in gene-interaction-networks with some genes interacting physically via their products or by functioning as regulators. These interactions have a key function to maintain stable gene expression and, more generally, this regulation of gene expression is a fundamental process to maintain cellular homeostasis and pleiotropy shaping the organism's phenotype. Besides these internal mechanisms, external factors and environmental factors influence or even regulate gene expression as well. One highly influential set of environmental factors is the diverse assembly of microbes surrounding and interacting with the organisms, the microbiome.

During the past 10-15 years, the microbiome was diligently investigated and a plethora of studies have contributed to our understanding of its role and effects on host organisms. The host not only provides an ecosystem for the microbiota but in return, the host derives beneficial effects from the diverse communities of bacteria, archaea, fungi, and viruses that live on and in the host (e.g., metabolites, developmental cues). However, we still lack a detailed understanding of the complex microbial interactions with its host. Particularly knowledge to which extend and through which mechanisms the microbiome acts as a regulator of gene expression is still mostly unknown. The expression of genes in the host and the microbiota has to be closely regulated as both sides continuously interact and shape each other's environment.

Thanks to advances in sequencing techniques over the past 15 years, we are able to study gene expression of model and non-model organisms in an almost unbiased manner. Furthermore, the development of high-throughput sequencing made it feasible to study the highly diverse and mainly uncultured microbiome on a large scale including many different host organisms and experimental setups. Commonly, the microbiome is described by using 16S amplicon sequencing but untargeted shotgun metagenomic approaches are getting more popular as sequencing costs drop. Furthermore, the use of naturally tractable host-microbiota associations and the continuous improvement of gnotobiotic and organoid model systems have additionally brought methods of experimental validation to the field of microbiome research.

This Special Issue should serve as a platform to bring together recent advances in the understanding of the dynamic interplay between gene regulation and host-microbiome interaction. We invite researchers to share their results on gene regulation by microbiome interactions. Besides experimental work, we would like to encourage researchers with a strong theoretical and modeling background to share their ideas and theories on interindividual and interspecies gene regulatory dynamics.

We are looking forward to your contributions to this Special Issue.

Dr. Axel Künstner
Dr. Philipp Rausch
Guest Editors

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• Microbiome/Microbiota
• Gene expression
• Symbiosis
• Dysbiosis
• Signaling Pathways
• Regulation of Gene Expression