Ciencias Exactas y Ciencias de la Salud

Breastmilk is a complex and dynamic fluid that supplies hydration, nutrients, and bioactives essential for the optimal growth and development of neonates. Breastmilk bioactives play pivotal roles in providing passive immunity against pathogens, fostering tolerance to nascent microbiota, and facilitating the maturation of the intestinal system. Maternal obesity, a significant health concern, has been linked to changes in breastmilk composition. Understanding the intricate dynamics of bioactive compounds in breastmilk. While previous research has often focused on analyzing individual breastmilk constituents separately, there is a growing recognition of the need for a more holistic approach that considers the systemic nature of breast milk. Specifically, investigating the interactions among different bioactives, such as microbiota and metabolites, is crucial for comprehending the overall composition and function of breastmilk. Colostrum, serving as the initial seed for neonatal gut microbiota establishment, holds particular significance in this context. Nonetheless, our current comprehension of how maternal obesity impacts breastmilk bioactives through a systems biology perspective is limited. This doctoral thesis aims to bridge this gap by examining the influence of maternal obesity on the co-occurrence patterns of colostrum bioactives, including microbiota, metabolites, and pro-inflammatory cytokines. Through collaboration with the Hospital Regional de Alta Especialidad Materno Infantil, we obtained two cohorts of volunteers from Monterrey, comprising 30 and 48 participants, respectively, who generously provided colostrum samples. These cohorts were sampled at different times, one from May to December 2019 and the other from October 2020 to July 2022. Samples were categorized into two groups based on BMI, classified according to the World Health Organization as normal weight (≤ 24.9 kg/m2) or obesity (≥ 30 kg/m2). Using co-occurrence networks and multi-omics approaches, specifically 16S-microbiota profiling, and untargeted metabolomics, we explored the compositional and structural changes within the colostrum ecosystem in the context of maternal obesity. Our study reveals that maternal obesity induces alterations in the ecosystem structure of colostrum. While normal weight conditions showed more positive correlations between pro-inflammatory cytokines and Proteobacteria members, such as Neisseriaceae, Pasteurellaceae, and Enterobacteriaceae, these correlations were absent in obesity samples. Microbiota diversity remained stable, with subtle shifts like reduced Proteobacteria abundance observed in colostrum from women with obesity. Furthermore, metabolite profile, particularly 15-HEDE, a lipid mediator involved in pro-inflammatory response, vasodilation and hyperpermeability, exhibited reduced abundances in response to maternal obesity, also show intricate associations with inflammatory-related cytokines (IL-12p70 and IL-10) and microbial taxa (Beijerinckiaceae and Burkholderiaceae). Additionally, our study highlights the importance of considering neonate sex bias in breastmilk microbiota research, as it influences the prevalence of specific bacteria such as Streptococcaceae, Xanthobacteraceae, and Burkholderiaceae. These findings underscore the connection between alterations in the bacterial community, metabolites, and inflammatory markerswithin the colostrum environment in the context of maternal obesity. Further research is necessary to elucidate the interactions between the host and bioactives in colostrum and their broader implications concerning maternal obesity.

Ciencias Exactas y Ciencias de la Salud

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