The WOMAN project addresses a frequent clinical condition with major societal impact: early musculoskeletal ageing (MSA) in post-menopausal women, characterized by the close and clinically inseparable association of sarcopenia and osteoarthritis. This combined condition leads to pain, functional limitations and a sustained deterioration in quality of life in women who are still largely professionally active, yet it remains insufficiently characterized and insufficiently integrated into current prevention and care strategies.
In this context, the gut microbiota (GM) is now recognized as a major determinant of host health, at the interface of diet, metabolism and physiology. Accordingly, the PEPR Food Systems, Microbiota and Health programme aims to structure integrated approaches to decipher its role in pathophysiology and to pave the way for new diagnostic and therapeutic tools. Interactions between the GM and skeletal muscle are now strongly supported by the literature, including work from the consortium, demonstrating the key role of intestinal bacteria and their derived metabolites in muscle function regulation. Converging evidence also increasingly supports the involvement of the GM in joint health.
Considering the GM as a structuring actor of female musculoskeletal ageing trajectories therefore constitutes the central scientific positioning of WOMAN, offering an innovative lever in a chronic and disabling pathology. The project relies on human-derived biological samples and clinical data, ensuring maximal translational relevance, and builds on solid preliminary data. It mobilizes advanced experimental, analytical and statistical approaches, enabling a fine and integrated characterization of microbiota–host interactions.
The project specifically aims to:
(i) Identify and validate microbiota-dependent biomarkers and bioactive compounds of musculoskeletal ageing (WP1) using a cohort of MSA patients compared with an age-matched healthy control group, combining clinical phenotyping, shotgun metagenomics and metabolomics, with integration of French Gut data to strengthen identified signatures and machine learning approaches to support early diagnosis and prioritization of microbial metabolites of interest.
(ii) Assess the causal inference of microbial ecosystems derived from MSA patients through human microbiota transfer into young, healthy murine models (WP2), in order to test their ability to induce a premature MSA phenotype in the host, providing a « gain-of-dysfunction » type demonstration of the role of the GM in early musculoskeletal ageing.
(iii) Functionally test and prioritize microbiota-dependent bioactive compounds with therapeutic potential in MSA (WP3) through modulation of human microbiota using anaerobic fermentation systems, coupled with testing in human muscle and joint cellular models. Effects on gut microbiota structure and functionality, as well as impacts on intestinal, muscular and joint physiology, will be compared between candidate compounds identified in WP1 and reference compounds supported by consortium data.
By integrating biomarker discovery, causal evidence and the prioritisation of microbiota-dependent therapeutic levers, the project delivers an innovative and coherent framework to advance diagnosis, prevention and targeted nutritional strategies in post-menopausal women.