Periodic Reporting for period 1 - MICROECO (Microbial ecosystems biology in the human gut)
Reporting period: 2023-01-01 to 2025-06-30
The gut microbiota has wide-ranging effects on host health and represents a promising target for therapeutic manipulation, particularly in early life. Imbalances in the gut microbiota precede the development of conditions such as overweight and immunological diseases, which exert a significant burden on society and on individuals. Early identification and treatment of gut microbiota imbalance in childhood thus offers great potential in combatting these problems, and will become an important part of health care in the future. However, achieving this goal will require a high-level understanding of the processes that regulate the microbial populations. Currently our knowledge of the principles governing gut microbiota responses to treatments is insufficient for reliable and targeted microbiota modification. In this interdisciplinary project, based on daily multiomic time series of child gut microbiota and diet and health diaries, we integrate the theoretical and analytical framework of population ecology, multiomic high-resolution quantitative microbiota profiling, and genome-scale metabolic reconstructions into an ecosystem model of the child gut microbiota. The result will be an unprecedented level of understanding of how the gut microbes interact and respond to external forces. The project represents the important next step in microbiota research from description to mechanistic understanding.
We have adopted into use two novel metagenomic library preparation methods to 1) enable inexpensive library preparation that makes it possible to sequence large numbers of samples, and 2) a meta-3C DNA extraction method that enables unprecedented detail in the annotation of metagenomic reads. We are currently working on analysing the data that these novel methods provide and are actively sequencing more metagenomes using these novel methods. The data will be used in all aspects of the project.
We are currently developing in silico models of bacterial metabolic interactions, which will be validated using culture-based phenotypic screening. We have identified suitable culture media and selective culture conditions for the major bacterial groups in the infant gut and have successfully isolated the bacterial taxa of interest from most of our samples. The first manuscript on bacterial culture work will be submitted in the next few weeks.
We have developed a phage enrichment protocol for infant feacal samples and are currently working on improving the protocol both in terms of efficacy of phage capture and throughput. The first manuscript regarding our phage work has been submitted.
We have developed a novel approach to investigating host-microbe interactions in vivo in the human gut by using time series of gut microbiota and faecal immune-related biomarkers. This was recently published (van Beek et al. 2024).
We identified the major developmental trajectories of infant gut microbiota and their later health associations in a large cohort of nearly 1000 infants (Hickman et al. 2024).
We also identified the impact of exposure to the environment on infant gut microbiota development using a cohort of infants born during the COVID-19 social restrictions (Korpela et al. 2024).
We are currently developing in silico models of bacterial metabolic interactions, which will be validated using culture-based phenotypic screening. We have identified suitable culture media and selective culture conditions for the major bacterial groups in the infant gut and have successfully isolated the bacterial taxa of interest from most of our samples. The first manuscript on bacterial culture work will be submitted in the next few weeks.
We have developed a phage enrichment protocol for infant feacal samples and are currently working on improving the protocol both in terms of efficacy of phage capture and throughput. The first manuscript regarding our phage work has been submitted.
We have developed a novel approach to investigating host-microbe interactions in vivo in the human gut by using time series of gut microbiota and faecal immune-related biomarkers. This was recently published (van Beek et al. 2024).
We identified the major developmental trajectories of infant gut microbiota and their later health associations in a large cohort of nearly 1000 infants (Hickman et al. 2024).
We also identified the impact of exposure to the environment on infant gut microbiota development using a cohort of infants born during the COVID-19 social restrictions (Korpela et al. 2024).
The time series approach developed during the project offers a novel way to investigate the gut microbiota and its interactions with the host with the potential to provide detailed information that otherwise would not be possible to achieve in vivo from humans. The approach can be adopted to other settings, as well, and used to answer many open questions. Further research is needed to fully demonstrate the utility of the approach and to identify the potential commercial solutions that may arise from such novel information.