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Louvain Drug Research Institute

PERIMETS/ARC

ldri | Bruxelles Woluwe

Impact of obesity and microbiota alterations on tumor peritoneal metastasis

Reference number : 25/30-151

Start Date : 01/10/2025

End date : 30/09/2030

Partners

PI (spokeperson) Pr Bénédicte Jordan, Université catholique de Louvain (UCLouvain), Louvain Drug Research Institute, Biomedical Magnetic Resonance Group (REMA)

Co-I 1 Pr Mireille Al Houayek, Université catholique de Louvain, (UCLouvain) Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids (BPBL)

Co-I 2 Pr Patrice Cani, Université catholique de Louvain (UCLouvain), Metabolism and Nutrition group (MNut)

Co-I 3 Pr Cédric Van Marcke, Université catholique de Louvain (UCLouvain), Institut de Recherche expérimentale et clinique (IREC)

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Aims of the Coordinated Research Project

The general aim of PERIMETS is to determine how obesity influences the metastatic spread of two obesity-associated cancers, invasive lobular breast carcinoma (ILC) and high-grade serous ovarian carcinoma (HGSOC), to the peritoneal cavity, and to translate this knowledge into novel, individualized therapeutic strategies for an increasingly large at-risk population. Building on preliminary data showing that obesity reshapes the peritoneal immune landscape in mice, with a reduction in large peritoneal macrophages, an influx of neutrophils and delayed resolution of inflammation, the consortium hypothesizes that the obese peritoneal microenvironment actively promotes metastatic progression through a combination of chronic low-grade inflammation, adipocyte-derived metabolites, altered tumor metabolism and microbiome dysregulation. A first specific objective is to compare, in obese and lean mice, the peritoneal metastatic potential of syngeneic models of both cancer types, using longitudinal bioluminescence and MRI metabolic imaging to capture tumor growth and metabolic adaptations in vivo, and to dissect the underlying mechanisms through methods including flow cytometry and lipidomics. This side-by-side comparison of two distinct tumor types sharing the same metastatic niche is expected to reveal both common and divergent pathways through which obesity shapes peritoneal dissemination. A second objective is to evaluate whether targeted modulation of the gut microbiome can counteract the pro-metastatic effects of the obese environment, by testing the impact of prebiotics and probiotics that have recently been shown by the consortium to decrease primary and metastatic growth of triple negative breast cancer in a mouse model of obesity. A third objective is to establish the clinical relevance of the findings through a translational proof-of-concept study in obese HGSOC patients, building on the an ongoing and on a prospective trial, combining spatial transcriptomics of peritoneal biopsies with microbiome profiling. Ultimately, by bridging preclinical mechanistic work and patient-derived data, PERIMETS aims to identify actionable targets, postbiotics, prebiotics and metabolic pathways, that could be exploited to prevent or limit peritoneal metastasis in obese patients, thereby paving the way for personalized therapeutic interventions in a population where the prevalence of both obesity and associated cancers continues to rise.

 

Prof. Bénédicte Jordan is a group leader in the Biomedical Magnetic Resonance group (REMA)
of the LDRI, specialized in the field of preclinical oncology, magnetic resonance imaging (MRI), and therapy monitoring. Together with Prof. P. Cani, with input from Prof. Van Marcke, she supervises 4 PhD theses addressing the link between obesity and Triple Negative Breast Cancer or melanoma progression. In the current project, she will bring expertise in tumor models, in the characterization of the tumor microenvironment, and the monitoring of tumor growth and metastatic progression using longitudinal non-invasive methods.

Prof. Mireille Alhouayek is a group leader in the Bioanalysis and Pharmacology of Bioactive
Lipids (BPBL) group of the Louvain Drug Research Institute (LDRI), specialized in the control of inflammation and macrophage activation using bioactive lipids. She is collaborating with Prof. P. Cani on the study of the role of bioactive lipids and microbiota in inflammatory bowel diseases. In the current project, she will bring expertise in the characterization of the peritoneal microenvironment and of inflammation resolution, that will be assessed in the context of obesity and peritoneal metastasis.

Prof. Patrice Cani is a group leader in the Metabolism and Nutrition group (MNut) of the LDRI,
expert in the field of metabolism, nutrition, and the gut microbiota. His research emphasizes the intricate relationships between gut bacteria and host metabolic health. Prof. Cani is already actively collaborating with each partner of the consortium. In the current project, he will bring expertise in animal models of obesity, in ex vivo models including adipose tissue explants, and in gut microbiota analysis and modulation, that will be assessed in the context of obesity and peritoneal metastasis.

Prof. Cédric Van Marcke is a medical oncologist working at Cliniques universitaires Saint-Luc,
Brussels, specialized in breast cancer and precision oncology. He is a translational researcher at IREC, with strong expertise in high throughput sequencing and bioinformatics. Together with Prof. P. Cani, and with input from Prof. B. Jordan, he is the promoter of a PhD thesis studying the interactions between CDK4/6 inhibition, gut microbiota and anti-cancer immunity. He established a collaboration with Dr.Mathieu Luyckx (Cliniques universitaires Saint-Luc, de Duve Institute) with recognized expertise in ovarian cancer. In the current project, Prof. Van Marcke will bring expertise in the establishment and characterization of the models to ensure translational relevance in the context of breast and ovarian cancer.

People funded by the projects:

2 PhD students: David Navarro San Augustin (promotors: B.Jordan & M. Alhouayek); Noémi Zuccaro (promotors : Cédric Van Marche & Mireille Alhouayek

1 technician (MNut group)

 

David Navarro San Augustin

Obesity-associated Peritoneal metastasis in ovarian cancer: Effects of Regulation of metabolism and microbiota

Thesis in progress

Noémi Zuccaro

Impact of obesity and associated inflammation on peritoneal metastasis and chemoresistance in ovarian cancer

Thesis in progress

ARC kick off meeting (Internal meeting), November 2025, Brussels Belgium

Internal meeting to present the project to new PhD students, tehcnicians, post-docs, and research logisticians involved in the PERIMETS project (with all ARC partners)

Contact

Pr Bénédicte Jordan, UCLouvain, Louvain Drug Research Institute.

benedicte.jordan@uclouvain.be