Chemical imaging-based insights into the human gut microbiome drug interaction network

Sprecher: Michael Wagner (Universität Wien)

Gastgeber: Andreas Peschel (CMFI)

Datum & Uhrzeit: 30.04.2026 | 12:30–15:00 Uhr

Ort:  Seminarraum Ebene 2, M3 Forschungszentrum, Otfried-Müller-Straße 37, 72076 Tübingen

Öffentliche Veranstaltung. Keine Anmeldung erforderlich. Nach den Vorträgen und der Diskussion findet ein kleiner Empfang in der EIngangshalle des GUZ statt.

Abstract: 

One of the biggest challenges in microbiome research is to understand functional properties of microbial community members at single-cell resolution. Single-cell isotope probing has emerged as a powerful approach for this purpose, but current methods for detecting isotope incorporation into single cells remain too slow for high-throughput analyses. Recently, we developed an imaging-based approach termed stimulated Raman scattering–two-photon fluorescence in situ hybridization (SRS-FISH) for high-throughput analysis of microbial metabolism and identity at single-cell resolution (Ge et al. 2022; PNAS). SRS-FISH achieves imaging speeds of 10–100 ms per cell, two to three orders of magnitude faster than state-of-the-art methods.

We applied SRS-FISH together with quantitative microbiome profiling and long-read metagenomics to investigate the effects of nervous system–targeted drugs on the human gut microbiome. Specifically, we studied entacapone, a catechol-O-methyltransferase inhibitor widely used in Parkinson’s disease therapy, and loxapine succinate, an antipsychotic used to treat schizophrenia and acute agitation (Pereira et al. 2024; Nat. Microbiol.). Ex vivo supplementation of physiologically relevant concentrations of either drug to faecal samples significantly affected the abundance of up to one third of the microbial species present. Importantly, SRS-FISH revealed that drug-induced effects on microbial metabolism are substantially stronger than effects on species abundances, with low drug concentrations reducing the activity, but not the abundance, of key microbiome members such as Bacteroides, Ruminococcus, and Clostridium species. Mechanistically, we show that entacapone perturbs microbial communities through its ability to complex and deplete ferric iron, and that microbial growth can be restored by replenishing microbiota-accessible iron. Notably, entacapone-induced iron starvation selectively enriched iron-scavenging organisms carrying antimicrobial resistance and virulence genes. In addition, I will present unpublished data on the effects of Parkinson’s disease drug combinations on the human gut microbiome, as well as studies in a mouse model examining how entacapone - either directly or via microbiome-mediated mechanisms - affects host immune responses. Together, these results demonstrate the power of next-generation chemical imaging to uncover drug-microbiome-host interactions and identify metal sequestration as an important mechanism of drug-induced microbiome disturbance.

Flash Talk:

Christoph Ratzke (CMFI)

Titel:

Sublethal Antibiotics Reshape Communities to Favor Pathogens

Abstract:

Antibiotic susceptibility is typically measured using pathogens grown in isolation, even though infections occur within complex microbial communities. Here, we show that sublethal antibiotic concentrations can paradoxically increase pathogen growth within microbial communities, despite inhibiting the same pathogens in monoculture. This effect arises because antibiotics reshape community composition by preferentially inhibiting strongly suppressive strains and by altering microbial interactions, making them more facilitative. Together, these changes weaken colonization resistance and support pathogen expansion. Importantly, we demonstrate that this effect can translate into increased host lethality following antibiotic treatment. Our results highlight that antibiotic efficacy depends strongly on microbial community context.