Impact of maternal obesity on early-life microbiota-induced immune system priming

Abstract

Early-life gut microbiota is highly modifiable, and subject to modulation by external factors such as maternal microbiota, mode of delivery, and feeding strategies. And important “window of opportunity” is established in the first 1000 days of life, in which the infant’s gut microbiota influences the development and maturation of the immune system. Thus, any disturbances to the gut microbiota during this period of development will have consequences for the child’s future health. The mother represents one of the main sources of microorganisms for the infant, and through the mechanism of vertical transmission of microbiota, it may transmit a dysregulated gut microbiota in cases of maternal intestinal dysbiosis. Considering the important role of the mother in establishing the infant’s gut microbiota, this study aimed to determine the impact of maternal obesity on the immunomodulatory ability of the infant’s gut microbiota. To achieve our aim, it was necessary to optimize the experimental protocols, namely, i) the separation of gut microbiota from infant stool samples and inactivation with UV radiation, and ii) the stimulation of monocyte-derived dendritic cells and T-cells with the extracted microbiota. Following protocol optimization, a set of fecal samples from infants of healthy (n=3) and obese mothers (n=3), collected over the first year of life (1, 6, and 12 months), were assessed. The preliminary results obtained through the stimulation of immune cells with a limited sample number of gut microbiota from infants of obese and lean mothers revealed that, although it led to immune cell activation, there were no significant differences between children from obese or lean mothers observed regarding to expression levels of activation markers of immune cells. In conclusion, this work allowed the optimization of an experimental protocol for evaluating the impact of maternal obesity on the immunomodulatory ability of the infant’s gut microbiota. Presenting only preliminary results it would be premature to assume that maternal obesity does not seem to influence the modulation of the immune system in early life, as it will be necessary to carry out more experiments with a larger number of samples to draw robust conclusions.

Date of Award	14 Feb 2023
Original language	English
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Ângela Margarida Amorim Costa (Supervisor) & Maria Benedita Almeida Garrett Sampaio Maia Marques (Supervisor)