Nutrition-Microbiome-Immunity Crosstalk

Diet plays important roles in promoting health and immune regulation, yet how nutrition influences the immune system in general, and macrophages in particular, is not well understood. Furthermore, the precise impact of diet on the microbiome, which then in turn also can influence immunity, remains mostly elusive. In order to develop precision-nutrition therapies to improve health and modulate the microbiome and immune system, understanding molecular mechanisms is essential.

In our previous work, we showed a remarkable divergence of the immune system in response to diet, in which a ketogenic diet significantly upregulated adaptive immunity, while a vegan diet significantly enhanced innate immunity in healthy human volunteers (Link et al., Nat Med, 2025). We are now expanding these investigations to mouse models to confirm that the impact of diet extends to the mouse system.

Our laboratory focuses mainly on the two most prominent barrier tissues – the gut and the skin. Both immunity in the gut and the skin are affected by a combination of nutrition and the microbiome, possibly modulating and priming immune response to external stimuli.

Furthermore, the CDC estimates that 3.1 million Americans are affected by inflammatory bowel disease (IBD) and 7.55 million Americans are affected by psoriasis with both disease on the rise. There is a strong connection between these two disorders with approximately 10% of inflammatory bowel disease (IBD) patients developing psoriasis. The development of precision-nutrition therapies to prevent disease onset in genetically susceptible patients and help manage disease symptoms in patients holds promise, requiring an understanding of the interplay between the immune system, and nutrition during inflammation. While some risk factors for the development of those diseases are known, the role of nutrition and the microbiome in disease development and severity remains unclear. Macrophages play important roles in the onset of inflammatory diseases and are influenced by nutrition and the microbiome, but the underlying mechanisms on how those factors influence the transcription factor networks remain poorly understood. Therefore, understanding the interplay of genetics, nutrition, and macrophage phenotypes is essential for developing precision-nutrition therapies.

The laboratory utilizes a comprehensive systems biology approach applying single cell multi-omics assays to investigate the interplay between the microbiome and nutrition on the epigenetic, transcriptional, and proteomic landscape in macrophages with the goal to identify the underlying transcription factor network, unique and conserved genes and pathways, as well as tissue-specific regulations, allowing direct comparison of the impact of nutrition and microbiome on tissues. In the long term, we will extend our studies by applying spatial transcriptomics methods to assess interaction of macrophages with other cells and broaden the studies to assess other immune cells.