Informal Seminar - Jonas Schluter

I am going to present our work on understanding the symbiosis between host and gut microbiome. I will show predictions arising from eco-evolutionary theory, how they inform our work on manipulating gut microbiome ecology, and how we are using high-temporal frequency measurements of cancer immunotherapy patients' microbiome and immune system to link their dynamics with approaches borrowed from ecosystem analysis (e.g. daily blood and stool samples from >1,000 patients).

We leverage cancer therapies as "natural experiments" wherein microbiome and immune system incur massive perturbations, which enables linking changes in one system to the other. With this, we uncover novel interactions that we hope to leverage to manipulate systemic immune function via manipulations of the microbiome. For example, we find that a) recovery of the hematopoietic system after chemotherapy is accelerated by obligate anaerobe commensals, b) peripheral blood monocytes upregulate inflammatory gene programs upon perturbation of bacterial and fungal gut populations. These insights—directly from patients—open new avenues to strategize novel microbiome therapies.

But we have few options to reliably manipulate microbiome communities. To solve this, we are a) quantifying the impact of diet on microbiome communities using >9,000 meals where each food item eaten was quantified to gram precision, alongside >1,000 longitudinal stool samples, and b) map microbial quorum sensing arsenals across all known gut bacteria, which we speculate might offer novel therapeutic strategies that work at low molarity.

Towards this, I will present results from a randomized controlled trial of an investigational new drug—a postbiotic, which is a complex fermentation product—that we designed by mimicking early life microbiome assembly dynamics, and which showed significant protection from antibiotic-induced microbiome damage in human subjects. These encouraging results are inspiring us to identify new molecular signals that enable a complex gut community to withstand external perturbations.

Finally, I will present unpublished work from a multi-year experiment in which we rear genetically controlled mice under defined gradients of microbiome diversity. This unique platform enables us to study epigenetic germline modifications induced by the microbiome, which we find to shape offspring development and pathogen resistance—revealing a novel dimension of host–microbiome symbiosis across generations.