Periodic Reporting for period 1 - MicroMI (Factors driving mother-to-infant microbiota transfer)
Okres sprawozdawczy: 2021-09-01 do 2023-08-31
MicroMI aimed to investigate the mother-to-infant transfer of microbiota during the first month of life and its role in infant’s gut microbiota composition and functionality and the consequences in infant’s development.
The gut microbiota, which is a complex community of microorganisms (bacteria, virus, fungi), that inhabit in our gut, have key functions in our body, including the development of the immune system, metabolism and maturation of the gastrointestinal tract (GIT). The establishment of the gut microbiota starts at birth and develops over time coinciding with the maturation of the GIT and immune system. Infant gut microbiota alterations have been linked to higher risk of noncommunicable diseases (NCDs) as allergy, obesity and cardiovascular diseases. NCDs are increasing and account for more than 41 million people deaths per year (71% of all deaths globally), being more critical in infants. Thus, early microbial colonization is essential for an optimal health. The mother is the main source of microbiota to the infant, representing a pivotal step in the development of infant gut microbiota. The study of the microbiota from mother-infant is key for understanding the function of these pioneering bacteria in the infant gut development. The data from MicroMI showed exciting ground-breaking results by performing state-of-the-art research. This project revealed that Bifidobacterium strains are highly isolated from mother-infant pairs and they showed more potential transference events than other microbial groups. The isolation of these strains allowed an in-depth understanding of the functionality and probiotic properties of these bacteria in the infant gut and the cross-talking with the host. Thus, MicroMi has originated a collection of Bifidobacterium strains genetically and functionally characterized with high value for the development of next-generation probiotics with known mechanisms of action. These strains can be used as new dietary interventions to treat or prevent a range of disorders and improve public health.
The gut microbiota, which is a complex community of microorganisms (bacteria, virus, fungi), that inhabit in our gut, have key functions in our body, including the development of the immune system, metabolism and maturation of the gastrointestinal tract (GIT). The establishment of the gut microbiota starts at birth and develops over time coinciding with the maturation of the GIT and immune system. Infant gut microbiota alterations have been linked to higher risk of noncommunicable diseases (NCDs) as allergy, obesity and cardiovascular diseases. NCDs are increasing and account for more than 41 million people deaths per year (71% of all deaths globally), being more critical in infants. Thus, early microbial colonization is essential for an optimal health. The mother is the main source of microbiota to the infant, representing a pivotal step in the development of infant gut microbiota. The study of the microbiota from mother-infant is key for understanding the function of these pioneering bacteria in the infant gut development. The data from MicroMI showed exciting ground-breaking results by performing state-of-the-art research. This project revealed that Bifidobacterium strains are highly isolated from mother-infant pairs and they showed more potential transference events than other microbial groups. The isolation of these strains allowed an in-depth understanding of the functionality and probiotic properties of these bacteria in the infant gut and the cross-talking with the host. Thus, MicroMi has originated a collection of Bifidobacterium strains genetically and functionally characterized with high value for the development of next-generation probiotics with known mechanisms of action. These strains can be used as new dietary interventions to treat or prevent a range of disorders and improve public health.
Results achieved in the MIcroMi work packages (WPs):
WP1. Determination of neonatal-breastmilk microbial composition and activity. The fellow got trained in state-of-the-art metagenomics. A culturomics approach was developed to isolate viable bacteria from mother-infant pairs during the first month of life. This approach allowed the identification of commensal Bifidobacterium as one of the main isolates from mother an infant gut microbiota. In depth phylogenetic analysis of the isolates allowed the identification of potential strains shared by the same mother-infant pair. This led to a collection of Bifidobacterium strains (100 strains approx.) with the whole genome sequence available for the functional analysis in the rest of the WPs.
WP2. Role of breastmilk in the establishment and functionality of GIT microbial pioneers. Selected strains from WP1 were tested for their capability of human milk oligosaccharides (HMOs) utilization and the interactions with the host (capacity of adhesion and inflammation effect). Bifidobacterium strains presented variability in HMOs degradation and for the first time it has been seen that strains of Bifidobacterium bifidum are capable to grow in all the HMOs tested, including the sialylated HMOs. Regarding the adhesion capacity, the strains of Bifidobacterium animalis showed the highest levels of adhesion to mucin in vitro. No inflammation was observed on cell lines.
WP3. Characterisation of probiotic strains able to transfer from mother-to-infant using an in vivo model. A protocol for screening beneficial properties of selected bifidobacteria from WP2 was established to test the utilization of a library of carbohydrates, the survival to simulated gastrointestinal digestion in vitro and the resistance to antibiotics. The results showed strain specific traits. One of the main objectives of MicroMI was to characterize in vivo the role of the bacteria transferred from mothers to infants in gut and immune system development. For that, an animal trial was carried out. Mice were fed with three different Bifidobacterium strains during pregnancy and lactation. Then, 2 weeks old mice were sacrificed to analyze the gut development and whole gene expression. The maternal treatment with a Bifidobacterium bifidum strain increased the body weight and the length of the colon and small intestine. Furthermore, this strain highly induced host response, specially genes involved in immune cells regulation and differentiation. This results open the window to the development of novel probiotic strains with commercial exploitation.
WP4. Communication and Dissemination of Results. There are two reviews published, one perspective submitted and there are three drafts in preparation (one systematic review, one research article and one guideline on early life microbiota acquisition). Also, there is a second paper expected to be published by 2024, as some of the experiments had to be postponed. The dissemination plan was discussed on regular meetings. The results from MicroMI has been presented in international and national conferences and workshops. The work carried out has been also shown to non-scientific audiences as a result of the participation in different outreach activities.
WP5 and WP6. These two WPs were Training and Career Development and Transfer of Knowledge and Management. All deliverables and milestones included have been achieved. Regular meetings with the group facilitated the evaluation of the project’s progress and to troubleshoot any issue related to all WP progression.
WP1. Determination of neonatal-breastmilk microbial composition and activity. The fellow got trained in state-of-the-art metagenomics. A culturomics approach was developed to isolate viable bacteria from mother-infant pairs during the first month of life. This approach allowed the identification of commensal Bifidobacterium as one of the main isolates from mother an infant gut microbiota. In depth phylogenetic analysis of the isolates allowed the identification of potential strains shared by the same mother-infant pair. This led to a collection of Bifidobacterium strains (100 strains approx.) with the whole genome sequence available for the functional analysis in the rest of the WPs.
WP2. Role of breastmilk in the establishment and functionality of GIT microbial pioneers. Selected strains from WP1 were tested for their capability of human milk oligosaccharides (HMOs) utilization and the interactions with the host (capacity of adhesion and inflammation effect). Bifidobacterium strains presented variability in HMOs degradation and for the first time it has been seen that strains of Bifidobacterium bifidum are capable to grow in all the HMOs tested, including the sialylated HMOs. Regarding the adhesion capacity, the strains of Bifidobacterium animalis showed the highest levels of adhesion to mucin in vitro. No inflammation was observed on cell lines.
WP3. Characterisation of probiotic strains able to transfer from mother-to-infant using an in vivo model. A protocol for screening beneficial properties of selected bifidobacteria from WP2 was established to test the utilization of a library of carbohydrates, the survival to simulated gastrointestinal digestion in vitro and the resistance to antibiotics. The results showed strain specific traits. One of the main objectives of MicroMI was to characterize in vivo the role of the bacteria transferred from mothers to infants in gut and immune system development. For that, an animal trial was carried out. Mice were fed with three different Bifidobacterium strains during pregnancy and lactation. Then, 2 weeks old mice were sacrificed to analyze the gut development and whole gene expression. The maternal treatment with a Bifidobacterium bifidum strain increased the body weight and the length of the colon and small intestine. Furthermore, this strain highly induced host response, specially genes involved in immune cells regulation and differentiation. This results open the window to the development of novel probiotic strains with commercial exploitation.
WP4. Communication and Dissemination of Results. There are two reviews published, one perspective submitted and there are three drafts in preparation (one systematic review, one research article and one guideline on early life microbiota acquisition). Also, there is a second paper expected to be published by 2024, as some of the experiments had to be postponed. The dissemination plan was discussed on regular meetings. The results from MicroMI has been presented in international and national conferences and workshops. The work carried out has been also shown to non-scientific audiences as a result of the participation in different outreach activities.
WP5 and WP6. These two WPs were Training and Career Development and Transfer of Knowledge and Management. All deliverables and milestones included have been achieved. Regular meetings with the group facilitated the evaluation of the project’s progress and to troubleshoot any issue related to all WP progression.
This project has exciting preliminary results that go beyond the current state-of-the-art and could potentially form the basis of an ERC Starting Grant application. Colonisation of the gut in the early stages of life is a critical event in the normal development of infant and imbalances n early gut microbiota have been linked to the development of non-communicable diseases. The underlying premise of MicroMI is that understanding the cellular and molecular effect of the early colonizers infant gut microbiota is of key relevance to provide microbiota-based probiotics to treat or prevent a range of diseases. MicroMI research showed that Bifidobacterium strains from mother-infant environment have potential for modulating gut microbiota composition and host response. Therefore, these results could have major implications for public health strategies by correcting the imbalances in early development of the microbiota. This cross-cutting interdisciplinary research directly relates to the objective of Horizon 2020 Work Programme (i.e. Social Challenge 1: Health, Demographic Change and Wellbeing) and Cluster 1: Health of Horizon Europe, which aims to promote an effective health campaign towards disease prevention. It could also contribute to finding therapies to treat or prevent NCDs.