Medical Systems Biology

Systems biology of inflammatory diseases: diabetes and IBD

Our research investigates how microbial-host interactions contribute to the onset and progression of inflammatory bowel disease (IBD) and type 2 diabetes. We are exploring the metabolic functions of the gut microbiome and the host, with the aim of uncovering therapeutic targets. For IBD, we study microbial metabolism and immune responses to develop interventions that can reduce inflammation and improve patient outcomes. In the context of type 2 diabetes, we focus on the gut microbiome’s role in metabolic dysregulation and how these microbial interactions relate to diabetes progression.

Systems biology of aging

Our research focuses on understanding the complex relationship between the gut microbiome and aging. We’ve identified critical changes in gene expression and microbiome activity that contribute to age-related health decline. In ongoing studies, we’re examining how microbiome interactions affect cognitive functions and healthspan during aging.

In our previous work, we have shown that aging alters gene expression in ways that promote degenerative diseases and reduce cancer risk, highlighting a genetic trade-off. Environmental enrichment (EE) and voluntary wheel running (VWR) have been found to significantly improve cognitive functions in old mice, with EE altering hippocampal gene expression and VWR reducing colon inflammation.

Additionally, we found that aging involves distinct phases of DNA methylation changes, characterized by an early-to-midlife and mid-to-late-life transition which largely involves epigenetic control of nervous system associated genes. We have also discovered that the metabolic activity of the aging microbiome declines, leading to reduced beneficial interactions and downregulation of critical host pathways. This underscores the importance of the microbiome in maintaining intestinal and overall health during aging.

Our ongoing research focuses on understanding microbial contributions to cognitive decline by examining the interactions between brain-resident microglia and the gut microbiome during aging, as well as exploring how social isolation, environmental enrichment, and exercise affect microbiome composition and cognition. Additionally, we are analyzing a mouse aging cohort aiming to reveal those systemic effects of aging, including changes in metabolic functions of the colonic microbiome, that relate to a decline in cognitive function.

Since 2024, our group, led by Dr Georgios Marinos and Professor Dr Christoph Kaleta, has been conducting a joint research project with Beiersdorf (Research Group Dr Elke Groenniger, Hamburg, Germany). The aim is to identify innovative modulators (compounds and/or genes) of skin ageing by integrating genome-scale metabolic modelling, high-throughput omics data, and skin microbiome information, followed by internal validation by the company’s research and development department. The project is implemented through the University’s knowledge and technology transfer company, CAU Innovation GmbH.

Finally, we are investigating the variation in taxonomic and functional microbiome profiles along the gastrointestinal tract and how aging blurs these microbial niches. Our long-term objective is to translate our insights into microbiome-based therapies to enhance cognition as well as health- and lifespan.

Steroid Hormones and the Gut-Brain-Axis

As women age, cessation of ovarian function leads to declining estrogen and progesterone levels, increasing the risk of cardiovascular disease, mood disorders, cognitive changes, and tissue atrophy such as osteoporosis, while simultaneously reshaping microbiome composition in the oral, vaginal, and gut niches. These hormone-driven microbiome shifts matter because the gut microbiome actively recycles host metabolites, including steroid hormones, and can re-activate conjugated estrogens via enzymes such as β-glucuronidases (Best et al., 2025; Cotton et al., 2023). Emerging evidence from human cohort studies and mechanistic gut–brain axis research links menopause-associated dysbiosis to cognitive decline, showing associations with increased neuroinflammation, altered tryptophan metabolism, and changes in microbial metabolites that modulate blood–brain barrier integrity and neurotransmission (Nieto et al., 2025). A deeper understanding of host–microbiome hormone interactions may open new intervention opportunities to preserve cognitive health and quality of life in menopausal women.Project-related publications

Modelling microbiome – host interactions

Our research explores host-microbiome interactions across various model organisms, aiming to understand how these interactions influence health and disease. We use metabolic modeling to study these interactions in the nematode Caenorhabditis elegans, focusing on nutrient absorption and genetic alterations. We also investigate the impact of proton-pump inhibitors (PPIs) on the gut microbiome of human users and assess the implications of these microbial changes. Additionally, we study the stable microbiome of the cnidarian Hydra to explore the ecological factors that influence microbial community dynamics.

Towards the rational design of microbiome-based interventions

Our research leverages genome-scale metabolic modeling to design targeted nutritional interventions aimed at modulating the microbiome in ways that promote host health. By using advanced models, we have already developed interventions that successfully increase the abundance of beneficial microbial species. Current projects aim to expand these findings to other host-associated species and human-relevant microbial communities.

While extensive research has been conducted on bacterial communities and their role in host health and disease, there is still limited knowledge about how this understanding can be translated into practical microbiome interventions. Building on our work in host-microbial interactions through genome-scale metabolic modeling, we are using these models to design targeted nutritional interventions.

In a proof-of-principle study, we developed a targeted intervention aimed at increasing the abundance of the host-beneficial species Pseudomonas lurida MYb11 in the microbiome of Caenorhabditis elegans. Using metabolic modeling, we identified a set of potential nutritional supplements that could promote the growth of this protective species. Among the supplements, serine was found to specifically increase the abundance of MYb11 both in vitro and in vivo.

Currently, we are expanding our research to include a broader test community of Caenorhabditis elegans-associated species. Additionally, we are investigating how these nutritional supplements affect a simplified human intestinal bacterial community (SIHUMI), which will help us understand the broader implications of our interventions for human health.