Microbial communities in the gut constitute a relatively stable and robust system and they are capable to recover after significant perturbations. This project is aimed to develop a series of interconnected short stays in the partner laboratories to study the modulatory effect on the gut bacterial populations of antibacterial peptides produced by gut bacteria and also by the host’s epithelium. Gut microbial profiles are associated to metabolic disease (obesity) but also may play a key role in the modulation and development of the immune system in infants; hence, model systems will be implemented and developed to test the effect of antibacterial peptides in such different scenarios. This Project will generate a number of natural molecules of bacterial, food or human origin (and bacteriophages) with a very valuable use for the maintenance of a healthy status in infants and adults, through the modulation of gut microbiota. The donor partner, Norwegian University of Life Sciences, have been working on bacteriocins from lactic acid bacteria and other gram-positive bacteria since early 90s. This partner is in the forefront of this research field.
Summary of project results
In health conditions, microbial communities in the gut appear to be relatively stable and robust, and they are capable to bounce back to its original state after significant perturbations (resilience). However, little is known about the factors that lead to homeostasis in the gut microbiota and the consequences of it for human health. Hence, the project explores the role of antimicrobial peptides, such as bacterial antagonistic peptides /bacteriocins) and how they contribute to control the composition of the microbiota. Investigations were also focused to determine the contribution of other key factors to the composition of the microbiota, such as bacteriophages, diet components and host mucosal immunity. This constituted an integrated multidisciplinary study that used proteomics, metagenomics, synthetic biology, immunological studies, in vitro, in vivo models and human studies. The project contributed to develop tools to control the microbiota in situations where the microbial balance is compromised, such as the perinatal period, when this balance is very fragile but yet is has a fundamental role for the health status in adult life. The project included the following work packages: 1) Influence of AMPs in the gut microbiota homeostasis: mechanisms of action and in vitro assays. 1.1.) Role of bacteriocins on bacterial populations balance in the gut and in vitro assays. 1.2) Investigate the basis of putative synergistic / antagonistic activities among bactoriocins. 2) Influence of bacteriophages, host mucosal immunity, diet components and other factors in the composition of the gut microbiota: mechanisms, in vitro assays. Besides exchanging ideas and future research challenges, partners sequenced the genome of the bacteriocins resistants mutants previously isolated. 3) Establishing the relationship between molecular factors that control bacterial populations, gut microbiota and health, Reshaping the gut microbiota towards healthy profiles: in vivo assays. 3.1) Characterization of bacteriocins that reinforme the probiotic potential of LAB in human and animals. 3.2) Distribution of conjungative plasmids and mobile genetic elements in Spanish preterm and full term infants. 3.39 Bioinformatic analysis of Clinical assay testing probiotics for prevention of allergies. Two manuscripts have been prepared and submitted to relevant journals and some other are in preparation.
Summary of bilateral results
The project was based on the complementary expertise of partners. As hosting partners, IPLA-CSIC provided access to and hands-on experience with in vitro model of gut microbiota. Similarly, LMG-NMBU research group share its interest and hands-on experience in bacteriocin research. The project has been very successful in all aspects. At scientific level, partners have been very productive, training and exchange states have been very fruitful and also scientists of the two countries have offered an excellent atmosphere and long lasting personal connections have been created. In this grounds, partners have already taken part in the call of the European Commission H2020- SFS-16-2015 with a proposal. The aim of the partners is to strengthen the cooperation pursuing common goals in different fields, namely: - Understanding the mother-infant microbiota and the impact of early life antibiotics in mobile elements - Gut microbiota variations as function of health and diet - The effect of antimicrobials to selectively displace specific bacterial populations with the gut microbiota or other complex ecosystems - Understanding bacteriocin resistance mechanisms - Role of bacteriophages in reshaping the microbial balance in the gut microbiota and other environments.