Menu
MapConnectionsTopicsBulgariaThe Night (K-TRIO)Marie Skłodowska-CurieFor studentsFor teachersMethodologySurprise me
HEIndividual fellowship2023–2025

MaterHypoBiota · Exploring the role of maternal gut microbiota on hypothalamic neurodevelopment and metabolic programming in offspring.

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-09-01 → 2025-08-31
EU contribution
€211,381
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

MaterHypoBiota: Exploring the role of maternal gut microbiota on hypothalamic neurodevelopment and metabolic programming in offspring.

The escalating high prevalence of metabolic disease, as obesity and type 2 diabetes, represents one of the most significant burden of modern society, given its impact on health and economy. Particularly troublesome is the high level of overweight and obesity in children. According to the latest WHO estimations (2022-2024), 1 in 4 children aged of 7-9 years is living with overweight or obesity. These estimations highlight the urgent need to better understand the mechanisms involved in the onset of these early pathological conditions, in order to develop more effective therapeutic intervention strategies aimed at halting the onset of juvenile obesity and prevent development of lifelong metabolic disorders. Although the causes of these metabolic disorders are complex and multifactorial and are not yet fully understood, an increasing amount of evidence suggest that alteration of the maternal environment during gestation and early post-natal life may disrupt the development of brain circuits, leading to enduring metabolic consequences in the offspring. Recent evidence linked maternal gut microbiota (mGM) with enduring consequences on social behaviour and cognition. However, whether mGM affects the development of hypothalamic circuits regulating energy homeostasis remains unknown. In addition, despite evidence suggesting that mGM is required for the development of blood-brain barriers, its role in the development of blood-hypothalamic barrier (BHB) has not been investigated. The overarching goal of MaterHypoBiota project is to characterize the role of maternal gut microbiota in the development of hypothalamic metabolic circuits and blood-hypothalamic barrier properties and whether it has long-term consequences on energy balance regulation in offspring (Fig1).

Data: CORDIS, © European Union

Project objective

The alarmingly high incidence of obesity, particularly in children, highlights the need to better understand the factors and mechanisms involved in the early development of this pathological condition. Accumulating evidence, including work from the host lab, support the idea that the maternal nutritional environment could influence the offspring’s susceptibility to develop obesity and related comorbidities in later life. In particular, there is growing appreciation that developmental malprogramming of hypothalamic neuroendocrine system by the perinatal environment represents a possible cause for these diseases. However, the mechanisms by which the maternal environment affects hypothalamic development and predisposition to obesity are still largely unknown. We hypothesize that the maternal gut microbiota (mGM) conditions, in the offspring, the development of hypothalamic structures with lifelong metabolic consequences. We will test this novel hypothesis by using two complementary animal models of impaired mGM: germ-free dams and dams with antibiotic-induced alteration of gut microbiota during pregnancy and lactation. We will assess neuroanatomical organization of hypothalamic feeding circuits, structural and functional development of blood-brain barrier as well as metabolic outcomes in the offspring. Finally, we will examine the cause and effect relationship between mGM and hypothalamic development and function by determining whether i) maternal fecal material transplant and ii) dams’ supplementation with specifically identified microbial metabolites prevent offspring’s neuroanatomical and metabolic alterations. Completion of this project will i) shed light on a new vertical role of mGM on hypothalamic neurodevelopment and metabolic programming and ii) identify new potential drivers leading to early-life metabolic disorders. Given the high prevalence of maternal antibiotic use and childhood obesity, this project could have a potential impact on public health.

Original text from CORDIS.

Participants

  • UNIVERSITE DE LILLE · LilleCoordinatorFrance

Links

Data: CORDIS, © European Union