# Use of microbiome analysis as a complementary endpoint in clinical trials

## TL;DR

This study shows that R-roscovitine affects the lung and gut microbiomes in cystic fibrosis patients in a dose-dependent way, even without impacting Pseudomonas aeruginosa.

## Contribution

The study introduces microbiome profiling as a potential exploratory endpoint in clinical trials of novel therapies.

## Key findings

- Dose-dependent shifts in beta diversity suggest subtle restructuring of microbial communities.
- Tannerella and Granulicatella elegans increased, while Streptococcus decreased with higher doses.
- Microbiome changes were observed despite no effect on Pseudomonas aeruginosa.

## Abstract

The ROSCO-CF study evaluated the safety and effect of oral R-roscovitine in people with cystic fibrosis chronically colonized by Pseudomonas aeruginosa. While no direct impact on the respiratory pathogen was detected, lung and gut microbiomes were analyzed to explore broader effects of the treatment. Sputum and fecal samples collected before and after treatment were examined using 16S rDNA sequencing. Despite overall stability in alpha diversity, dose-dependent shifts in beta diversity suggested subtle restructuring of microbial communities. Temporal analyses indicated emerging patterns in microbial coordination at higher doses. Specific taxa, such as Tannerella and Granulicatella elegans, showed increased abundance, while Streptococcus decreased with dose. These results suggest that R-roscovitine may influence microbial dynamics in a personalized and dose-dependent manner, supporting the inclusion of microbiome profiling as an exploratory endpoint in clinical trials.

•Lung microbiome analysis shows dose-dependent shifts with R-roscovitine in cystic fibrosis•No detected effect on P. aeruginosa infection in the initial clinical trial•Highlights microbiome outcomes in early-phase trials of novel therapies

Lung microbiome analysis shows dose-dependent shifts with R-roscovitine in cystic fibrosis

No detected effect on P. aeruginosa infection in the initial clinical trial

Highlights microbiome outcomes in early-phase trials of novel therapies

Health sciences; Medical microbiology; Medicine; Respiratory medicine