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The Power of Maternal Microbes on Infant Health

Periodic Reporting for period 4 - MAMI (The Power of Maternal Microbes on Infant Health)

Okres sprawozdawczy: 2019-12-01 do 2020-12-31

"Recent reports suggest that early microbial colonization has an important role for in promoting health. This may contribute to reduce the risk of chronic diseases such as obesity, allergies and inflammatory conditions. Advances in understanding host-microbe interactions imply that maternal microbiota plays a crucial role on health programming. This process begins in utero and it is modulated by mode of delivery and early diet. Delayed microbial colonization and/or alterations in the microbiota profiles and lower microbial diversity are strong risk factors for the development of life-style diseases such as allergies, obesity, and metabolic syndrome. It is also suggested that early nutrition exerts both short- and long-term effects on human health in programming its immunological, metabolic and microbiological development. Thus, a key relationship between diet, microbiome, immune system and origins of human disease is a research priority. Further, breast milk carries a significant amount of bacteria that will constitute an important source of bacteria for the infant. The hypothesis of ""programming"" during prenatal and postnatal period needs to be substantiated, where breast feeding would have a relevant role. Therefore the main goal of this project is to unravel the role of maternal microbiota on infant health programming. Results obtained will demonstrate the interaction between infant nutrition, microbes and host response in early life and its key role in health programming, enabling new applications in the field of personalized nutrition & medicine.
The overall objective of this multidisciplinary research is to analyze early host exposition to bacteria, focusing on breast milk as the main vehicle for bioactive compound transfer to the infant and for shaping the development of the intestinal microbiota. The specific aims of this project are: (1) understanding how the maternal microbiome is influenced by host and environmental factors; (2) characterizing the microbial core and other compounds transmitted to the offspring via breastfeeding and their roles in the microbial modulation and host response; (3) understanding the interactions among breast milk bioactive compounds and their role for infant health; (4) shedding light on how maternal microbes influence the infant immune system; and (5) development of new dietary strategies and therapies based on microbial replacement and modulation. The technological advances in genotyping, expression profiling and metagenomics coupled with systems biology, anticipate high chances of success. The ambitious goals of this project will be broken down into specific tasks, involving different technical approaches and resulting in specific deliverables. This project will provide completely new integrative data on host microbial ecology and nutrition, genotype, immune system & metabolism to understand the origins of disease, focusing on the fetal period and the influence of mother."
MAMI is a prospective mother-infant birth cohort in the Spanish-Mediterranean area. Mothers were enrolled at the end of pregnancy and families were follow-up during the first years of life. Maternal-infant biological samples were collected at several time points from birth to 24 months of life. We have recruited already more than 250 mother-infant pairs, which represents more than 100% of the expected minimum size of MAMI cohort (n=100). To ensure a successful dissemination activities, we have conducted a large number of communication activities, training session in hospitals, healthcare centers, etc. which was important to engage volunteers and other participants (healthcare professionals, etc.).
MAMI main work-packages are:
• WP1. Mother-Infant Microbiota: Diversity, function and metabolic activities
• WP2. Mother-infant non-microbial components.
• WP3. Host factors in mother & infant
• WP4. Global data integration & Follow-up

MAMI results have shown that maternal diet plays a key role on maternal microbiota and intestinal homeostasis as well as the initial microbial inoculum for infant gut development with potential consequences in later life. Indeed, the distinct microbial inoculum also had an impact on the risk of obesity later in life in a mode of delivery dependent manner, being the C-section neonates the most sensitive ones. In brief, C-section neonates from mothers with more adequate diets shaping specific microbiota presented lower risk of overweight at 18 months age. In lay terms, if mother is going to have a C-section, please, take care of your diet as your microbes would have an impact on offspring development.MAMI results also showed that mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. Breast milk bioactive compounds were also modulated by maternal diet and perinatal factors having an impact on infants microbiota development. In summary, MAMI highlight the relevance of maternal microbiota on infant microbiota composition and infant growth. MAMI also reported data on the potential perinatal factors shaping maternal mcirobiota being the diet the most relevant one. In this scenario and taking into account that most of the actual evidence is focused on neonates, MAMI demostrated the relevant role of mothers showing that we need to consider mother-infant pair as a single group during early life. All situations and factors altering maternal microbes are going to be reflected in the neonate with consequences for infant growth, development and health. MAMI data warrants further studies focused on maternal side.
Information on host-microbe interaction will promote a deeper understanding on the risk of disease and may ultimately result in the discovery of new therapeutic targets. The project will provide new data in order to i) understand the effect of early environment factors, maternal microbes and diet, on short- &-long-term effects upon host’s health modulating microbial, immunological and metabolic programming, ii) to understand the role of microbes in nutritional, immunological & metabolic programming at certain life stages with health consequences later in life and even for subsequent generations. Work on each of these key questions provides important leads for the future.
MAMI expect that the milestones reached will reinforce the notion that nutrition in early life (breastfeeding practices) and the human milk bioactive factors might be exploited to promote microbiological, immunological and metabolic programming of child health and will inform the development of new dietary strategies, functional foods and therapies enabling new applications in the field of personalized nutrition and medicine aimed.
MAMI will have a great social impact and the knowledge created via this project will help to develop new strategies to reduce the risk of disease, to develop health policies and also to save money from public health resources. EU policies and H2020 priorities are often focused on elderly people or particular diseases, such as obesity. With this project we aim for the prevention of the development of specific diseases but also to maintain a good health throughout to arrive well to elderly ages.
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