The Microbiota Interactions with Human and Animal (MIHA) team at INRAE is interested in studying the interactions between the intestinal microbiota and its host and their role in digestive inflammation. More specifically, we are focusing on analyzing the functions of the microbiome that are modulated in inflammatory conditions. In this context, the team is analyzing the key role of the proteolytic imbalance observed in patients with inflammatory bowel diseases and inflammatory bowel syndrome. To this end, we are isolating genes and/or bacteria signatures that are associated to these diseases and are exploring their effects on the holobiont (host and its microbiota) response. We are also investigating the impact of food and diet as a source of proteases and antiproteases that could be used to restore proteolytic homeostasis.
Inflammatory bowel diseases (IBD) are multifactorial digestive disorders whose incidence is increasing worldwide and whose treatments are costly and non-curative. Existing therapeutic approaches have variable efficacy and patients can develop resistance to treatment (e.g. resistance to corticosteroids). New therapeutic approaches are thus needed. We have previously shown that proteolytic activities were increased in IBD patients and in a mouse model, that restoration of the proteolytic balance significantly reduced intestinal inflammation. Moreover, we demonstrated that genes from human gut microbiota encoding for serine proteases were more abundant in IBD patients compared to healthy subjects. We recently analyzed the proteolytic activities in IBD individuals, and found separate groups defined by their inter-individual proteolytic profile variability. These groups are potential targets to design tailored protease inhibitor therapies aimed at restoring the proteolytic balance, thereby reducing intestinal inflammation.
To achieve this objective, the MIHA team is drawing on its expertise in biochemistry, microbiology, biostatistics and pathophysiology. Our knowledge of ex vivo (Gut-on-Chip) and in vivo models, including preclinical animal models, is one of the team’s areas of expertise. The team relies on strong collaborations with human clinicians to construct large cohorts of patients.
With the advancement of microbiome research in recent decades, many attempts have been devoted to the identification of the main factors shaping commensal microbiota in the gut. Among the multiple factors involved, diet appears as a pivotal determinant of the structure and function of the gut microbiota community in healthy and pathological conditions. Our team is investigating food-microbiota-human interactions in chronic digestive inflammation. One central line of research concerns the role of food proteases and antiproteases in gut microbiome dysbiosis, barrier dysfunction, and proteolytic imbalance in IBD. We also aim to explore underlying mechanism of fermented food in modulating the inflammatory response.
All the team publications are available in the MIHA-MICALIS HAL collection.
WO2022058372A1 • 2022-03-24 • Parabacteroides distasonis strains for use thereof in the treatment and prevention of gastrointestinal diseases and of disorders associated with gastrointestinal diseases
