Pathophysiology of Nutritional Adaptations (PHAN)

Mission and Objectives

The first 1,000 days of life, including pregnancy, are a critical period for the development of the fetus, newborn, and child, and also contribute to their future health.

PhAN’s objective is to determine how early-life events (during the fetal and neonatal periods)—such as malnutrition, exposure to xenobiotics (medications, pesticides), and the parents’ metabolic status—increase the risk of cardiometabolic (diabetes, obesity, hypertension) and psychiatric disorders later in life. This programming involves a “memory” of these perinatal events, which is thought to be carried by epigenetic marks as well as by structural defects in key organs involved in metabolic regulation. The PhAN UMR studies the programming of the microbiota-gut-brain axis and its role in the risk of adult diseases.

More specifically (though not exclusively), the unit explores the effects of perinatal malnutrition using a translational approach (animal models, follow-up of pediatric cohorts). The importance of placental flux and breast milk in these processes is being studied.

Features of PhAN

• Among the many laboratories exploring the concept of DOHaD (Developmental Origins of Health and Disease), the PhAN UMR is unique in that it views young children not only as future adults at risk for long-term chronic disease, but also as individuals/patients in their own right, for whom nutrition is a primary concern for clinicians caring for pregnant women or children.

• The UMR PhAN is one of the few teams to address the “programming” of the microbiota-gut-brain axis.

• The UMR PhAN has been one of the first units to combine multiple experimental and multi-omic approaches in support of translational and clinical research within the framework of the DOHaD concept for the past 10 years.

• Under the leadership of the UMR PhAN, perinatal nutrition has become the “flagship theme” of the CRNH Ouest (www.crnh-ouest.fr).

• The UMR PhAN has helped organize local research on the microbiome over the past 5 years.

• The UMR PhAN is contributing locally to the growing interest and enthusiasm in the region, at the University, and at the University Hospital (CHU) regarding nutrition and health, by focusing on a critical life stage for disease prevention.

Research

Our research is both basic and translational (from the incubator to the lab bench and back again). PhAN’s objectives are to demonstrate, elucidate, and prevent—using preclinical models and human cohorts—the effects of nutritional and metabolic status from gestation through birth on development, major physiological functions, and the risk of diseases later in life.

We are searching for biomarkers of this nutritional programming using comprehensive “omics” approaches and bioinformatic analyses (integration of multiple clinical and molecular datasets) that enable us to predict, within a high-risk population, which individuals will develop a chronic disease. We are studying the mechanisms that may be involved—epigenetics, cellular and molecular alterations in organs, and early modulation of the microbiome and the immune system.

Finally, strategies to prevent or correct this programming are implemented through nutritional supplementation. The unit’s research themes are organized into four closely interrelated areas:

• Research Area A: To demonstrate the impact of parental nutrition and metabolic status on nutrient transport and metabolism, the epigenetic regulation of gene expression, and its consequences for the child’s growth, metabolic health, and psychocognitive development

• Research Area B: Understand the mechanisms by which the mother’s nutritional and metabolic status influences intestinal function (barrier integrity, endocrine and immune functions) and the risk of digestive disorders (chronic inflammatory diseases, etc.) and metabolic disorders (dysregulation of food intake and energy homeostasis)

• Research Area C: Understanding the mechanisms by which the mother’s nutritional and metabolic status influences cognitive function and the development of eating behaviors

• Research Area D: Demonstrating the role of the microbiota as an early determinant of mental and metabolic health