Periodic Reporting for period 1 - IAPEMIDE (Impact of Intrapartum Antimicrobial Prophylaxis as an early determinant in Microbiome Development)
Période du rapport: 2017-08-01 au 2019-07-31
During the last decades, changes in diet and lifestyle have increased the risk of non-communicable diseases (NCD) in the western countries. It is known that once these NCD are established in the childhood, they continue into adult life with the associated negative impact on health, quality of life and health care costs. The gastrointestinal tract (GIT) is not just the place where the digestion takes place, it is an important endocrine organ which harbours a very complex and dynamic microbial community, the so called intestinal microbiota (IM). The GIT-IM interaction results essential during early life for the development of a fully functional immune system and the maintenance of the host physiological homeostasis and health. The correct establishment of the IM in the early days of life plays an important role in the reduction of chronic disease, such as obesity, allergies, infection, inflammatory or brain disorders. Moreover, the early stage of life constitutes a critical window-of-opportunity for IM modulation towards a healthy profile. This fact entails the need to fully elucidate the factors driving the initial establishment and later development of the intestinal microbial community from the very early days of life. Several factors affecting this process have been extensively assessed; however, other specific perinatal factors like the intrapartum antimicrobial prophylaxis (IAP), in spite of been present on over 30% of total deliveries, have been much less studied. A large body of evidence supports that postnatal antibiotic administration to babies induce an irreversible disrupt of the natural microbiota succession and delay in the IM maturation, associated with NCD. Nevertheless, the effect of perinatal antibiotic administration to mothers during delivery as prophylaxis (IAP) still remained to be elucidated. On the other hand, the antibiotic resistance (AR) is nowadays rising to hazardously high levels in all parts of the world and is one of the main threats to global health. Different approaches have to be taken at all levels of society to reduce the impact and limit the spread of resistance. The IM can be considered as a reservoir of antibiotic gene resistance (ARG), and elucidating how the antibiotic exposure since the beginning of life is affecting this pool of gene is also of great importance. IAP is an effective procedure, used since the 80s, for the reduction of the neonatal mortality by invasive Group B streptococcal disease when mothers are colonized; however, it is also frequently used in other clinical situation in which a clear benefit has not been demonstrated.
The MSCA-funded IAPEMIDE project aimed to elucidate the impact of the IAP (a) on the IM establishment in the neonate, and (b) on the human antibiotic resistant genes reservoir (resistome) establishment at early stages of life. To investigate these questions, the following objectives were suggested: a) to identify the alterations induced by maternal IAP in the neonatal IM development; b) to study the potential role of infant feeding in the modulation of the microbiota´s effects derived of IAP administration; c) to identify the antibiotic resistance genes (ARG) that the IM carried as consequence of this early treatment; and d) to design specific dietary strategies for minimizing the impact of this common and potentially deleterious clinical practice on the IM establishment.
The MSCA-funded IAPEMIDE project aimed to elucidate the impact of the IAP (a) on the IM establishment in the neonate, and (b) on the human antibiotic resistant genes reservoir (resistome) establishment at early stages of life. To investigate these questions, the following objectives were suggested: a) to identify the alterations induced by maternal IAP in the neonatal IM development; b) to study the potential role of infant feeding in the modulation of the microbiota´s effects derived of IAP administration; c) to identify the antibiotic resistance genes (ARG) that the IM carried as consequence of this early treatment; and d) to design specific dietary strategies for minimizing the impact of this common and potentially deleterious clinical practice on the IM establishment.
This report concerns the actions carried out during the two years of the research project; however, IAPEMIDE is still currently on-going and different results are still being analysed. Faecal samples were collected at different times during the first year of life, and together with samples from previously recruited infants available in the research group, were analysed. Gut microbiota composition analyses revealed alterations on the IAP-group of babies with respect to control group, not only at high taxonomical levels but also at species level. To explore the metabolic implications of the IAP, the main metabolites of the gut microbiota were determined, metabolic pathways were reconstructed and a group of immunological components (chemokines, immunoglobulins and growth factors) were assessed. On the other hand, the abundance of different antibiotic resistance gene (ARGs), enzymes and transporters involved on the antibiotic resistance were assessed; moreover, the main beta-lactam ARGs present on the gut microbiota of infants were also quantified using q-PCR methods developed whitin the project. Based on the preliminary analyses of our results, a strong detrimental effect is observed in the microbial community composition and functionality from babies whose mothers were administered with IAP. With the objective to reduce the alterations observed in the gut microbiome, an in vitro faecal-culture with faecal samples from IAP-babies at 1 month old and selected potential probiotics isolated from faeces o breast-milk were already carried out and the analysis of data is still on-going. The dissemination plan included a good number of activities, such as presentations in national workshops (Sociedad Española de Probióticos y Prebióticos (SEPYP), 2018; SEPYP, 2019); international congresses (International Conference On Pediatrics & Neonatology, 2018, Rome, talk by invitation) and abstract accepted for the World of Microbiome Conference (WoMPBI) 2019, Milan; delivered talks in the Pint of Science event (2018, Spain), also for local audience and schools; among others. Manuscripts are in preparation.
The overall hypothesis presented in this project, “the IAP has a detrimental effect on the initial gut bacterial colonization and later health and is a driver of the human antibiotic resistant genes reservoir (resistome) establishment at early stages of life” was original and novel itself. Preliminary analyses from the results obtained confirm previous hypothesis and the information produced by IAPEMIDE will be of great value to the scientific and health care professionals. IAP is an important clinical practice for the infections prevention; however, the effects in the correct establishment of the IM, antimicrobial resistances and on later health have been undervalued by the clinical community. This research will provide unique information on microbiome and resistome affected by IAP and those results could help in the identification of consequences of IAP. These valued findings will provide information to doctors, who will be better able to address the consequences to make knowledge-based decisions about IAP treatment in those situations where it is not extremely mandatory. Furthermore, the on-going analysis of data will shed light on the role of breast-feeding in the IAP practice and will provide the basis for develop new dietary strategies based on microbial modulation through potential probiotic strains with the objective to minimize the effect of one of the most common practices in the daily hospital environment. On the other hand, the project were performed in a multidisciplynary environment and further ideas and, national and international collaborations, have arisen for keeping on analyzing the samples generated by this project. These findings contribute to the attainment of EU strategic goals.