Improvement of intestinal integrity and metabolic function by galactose
Metabolic diseases pose an increasing burden on health and economics worldwide. Therefore, preventive measures that reduce and delay the onset of these diseases must be extensively investigated. For example, nutritional interventions starting at infancy can be a successful strategy to prevent later‐life dysfunctions, such as obesity and associated diabetes. After birth, critical timepoints in the offspring’s development include lactation, weaning, and early post weaning. Nutrition, and particularly breast feeding, during these periods plays a major role, with short‐ and longterm beneficial health implications. In this context, dietary galactose, a monosaccharide naturally present in milk as part of lactose, has been shown to have beneficial effects on fat mas gain, hepatic health, and insulin resistance. However, little is known about how galactose affects intestinal health and whether changes in the intestinal homeostasis are responsible of the previously observed systemic positive effects of galactose. To fill this knowledge gap, we will conduct several mouse studies in which young mice will be fed isocalorically either a galactose containing diet, a lactose containing diet, or a control diet. We aim to determine how (ga)lactose affects metabolic health and more specifically intestinal health, by studying its molecular effects on the intestinal inflammation, intestinal barrier function and the microbiome, and its connection to liver and adipose tissue. In this project we will perform gene and protein expression analysis with physiological measurements like in vivo non‐invasive indirect calorimetry and ex vivo oxygraphy measurements. Together with omics techniques oriented to gain insight in the (ga)lactose‐induced differences in the microbiota composition and activity. Based on these new insights, our project will contribute to the development of nutrition‐based approaches to prevent metabolic diseases in the short‐ and long‐term.
We aim to determine how (ga)lactose affects metabolic health and more specifically intestinal health, by studying its molecular effects on the intestinal inflammation, intestinal barrier function and the microbiome, and its connection to liver and adipose tissue. In this project we will perform gene and protein expression analysis with physiological measurements like in vivo non-invasive indirect calorimetry and ex vivo oxygraphy measurements. Together with omics techniques oriented to gain insight in the (ga)lactose-induced differences in the microbiota composition and activity. Based on these new insights, our project will contribute to the development of nutrition-based approaches to prevent metabolic diseases in the short- and long-term.
Globally, a large fraction of infants and toddlers do not tolerate lactose, the main carbohydrate component of human milk. Infant and toddler nutrition provided as lactose-free products therefor lack the carbohydrate galactose. We showed previously that galactose has beneficial health effects, both as direct effects, as well as via nutritional programming: into adulthood when challenged by an obesogenic diet the early-life intake of galactose showed pronounced effects. Addition of galactose in infant and toddler nutrition might provide a way to also support those vulnerable populations and improve intestinal health. This is investigated in the current project.
Ethical permission will be asked for and granted (2021); once all diets and consumables are delivered to execute the first pre-clinical nutritional study, the study will be performed (early 2022), physiological and molecular data analyzed, resulting in a publication (deliverable, 2022). This will be followed on by other studies and publications, finished with publication of a PhD thesis (2022-2025).