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Immune imprinting by metabolites: unlocking new pathways for bone and development

Prof. Ziad Al Nabhani, Immunologist, Assistant Professor, and ERC Starting Grant Fellow at the University of Bern, Switzerland

2025

Early childhood is a key period for the development of the immune system, skeleton, and brain, with nutrition and the gut microbiota playing central roles. During the transition from milk to solid food (weaning),a distinct immune response, known as the "weaning reaction", emerges alongside increased microbial diversity and the production of bioactive metabolites, including polyamines (putrescine, spermidine, and spermine). Polyamines, produced by gut microbes, are essential for immune cell development, bone remodeling, and neurodevelopment.

Study Aim

This study aims to elucidate the role of microbiota-derived polyamines in shaping early-life B cell development and how these immune cells regulate bone remodeling and cognitive function.

Scientific Approach

Using mouse models to investigate how microbiota-derived polyamines influence early-life B cell development in the bone marrow, and determine the role of polyamine-modulated B cells in bone remodeling &skeletal development, as well as to assess the impact of early-life polyamine exposure on cognitive function & autism-like behavior.

Expected outcomes

This study will reveal how microbiota-derived polyamines influence immune imprinting, skeletal integrity, and cognitive development during early life. The results may pave the way for microbiota-targeted nutritional or probiotic interventions to promote immune resilience, prevent bone-related diseases, and improve neurodevelopmental outcomes in children.

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Funded projects

The Mother-Offspring Microbiome (M-OM) and Neurobehavioral Development

Brain Development, Infant Gut Health

Prof. Jeffrey Alberts, Professor of Psychological and Brain Sciences, Indiana University, USA

It is common for pregnant mothers who deliver prematurely to be treated with antibiotics during their pregnancy and postnatally. And it is well-documented that the premie population is strikingly dysbiotic and at great risk for a range of disorders including cognitive difficulties, feeding problems, GI disease, as well as disorders of social development. The efficacy of the oligosaccharide milk constituent, 2’-fucosyllactose (2'-FL), in resetting a healthy trajectory of neurobehavioral development will be studied.

Early-life susceptibility of brain epigenetic profiles to antibiotic treatment. Relevance for neurodevelopmental diseases.

Brain Development

Prof. Francesca Lembo, Associate Professor in Microbiology and Clinical Microbiology, University of Naples Federico II, Italy.

Antibiotics (ABs) represent the most common type of medication used during infancy. ABs have been proposed as a possible factor playing a role in the etiology of neurodevelopmental disorders (NDDs) promoting long lasting adverse effects on brain development. It has been claimed that AB use during early life may have a detrimental effect on the gut-brain axis by interfering with regular gut microbiota (GM) colonization.

Human Milk Oligosaccharides (HMOs) and probiotics on neonatal immunological imprinting

Infant Immunity

Prof. Gérard Eberl, Professor of Immunology, Institut Pasteur, France

The microbiota plays a key role early in life for the development of the immune system. Dietary weaning (the transition from a milk only diet to a diversified diet) induces a vast expansion of the microbiota and in response, a vigorous immune reaction termed the “weaning reaction” (WR). Early life treatment with antibiotics interferes with this early life immune response to the microbiota, and diets that lack fibers or that are excessively rich in lipids, lead to pathological imprinting later in life.

Discover all funded projects