The neonatal microbiome in utero and beyond: perinatal influences and long-term impacts

The neonatal microbiome offers a valuable model for studying the origins of human health and disease. As the field of metagenomics expands, we also increase our understanding of early life influences on its development. In this review we will describe common techniques used to define and measure the microbiome. We will review in utero influences, normal perinatal development, and known risk factors for abnormal neonatal microbiome development. Finally, we will summarize current evidence that links early life microbial impacts on the development of chronic inflammatory diseases, obesity, and atopy.

Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health

Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and ‘Mother Nature’ provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship.

Manipulating the neonatal gut microbiome: current understanding and future perspectives

The development of a healthy intestinal microbiome following birth contributes to the overall health of the infant during childhood and into adulthood. However, modern birth practices such as caesarean delivery, feeding, antibiotic exposure as well as maternal factors have the potential to greatly impact infant microbiome development. Aberrant microbiome development may be a key factor in the increasing incidence of inflammatory and gut diseases. This review will summarise the current understanding of how modern birth practices may contribute to deficiencies in neonatal gut microbiome development and will also present potential methods of microbiome engineering that aim to ensure the development of a healthy and robust microbiome to protect the host from disease throughout their life.

Impacts of the Marine Hatchery Built Environment, Water and Feed on Mucosal Microbiome Colonization Across Ontogeny in Yellowtail Kingfish, Seriola lalandi

The fish gut microbiome is impacted by a number of biological and environmental factors including fish feed formulations. Unlike mammals, vertical microbiome transmission is largely absent in fish and thus little is known about how the gut microbiome is initially colonized during hatchery rearing nor the stability throughout growout stages. Here we investigate how various microbial-rich surfaces from the built environment “BE” and feed influence the development of the mucosal microbiome (gill, skin, and digesta) of an economically important marine fish, yellowtail kingfish, Seriola lalandi, over time. For the first experiment, we sampled gill and skin microbiomes from 36 fish reared in three tank conditions, and demonstrate that the gill is more influenced by the surrounding environment than the skin. In a second experiment, fish mucous (gill, skin, and digesta), the BE (tank side, water, inlet pipe, airstones, and air diffusers) and feed were sampled from indoor reared fish at three ages (43, 137, and 430 dph; n = 12 per age). At 430 dph, 20 additional fish were sampled from an outdoor ocean net pen. A total of 304 samples were processed for 16S rRNA gene sequencing. Gill and skin alpha diversity increased while gut diversity decreased with age. Diversity was much lower in fish from the ocean net pen compared to indoor fish. The gill and skin are most influenced by the BE early in development, with aeration equipment having more impact in later ages, while the gut “allochthonous” microbiome becomes increasingly differentiated from the environment over time. Feed had a relatively low impact on driving microbial communities. Our findings suggest that S. lalandi mucosal microbiomes are differentially influenced by the BE with a high turnover and rapid succession occurring in the gill and skin while the gut microbiome is more stable. We demonstrate how individual components of a hatchery system, especially aeration equipment, may contribute directly to microbiome development in a marine fish. In addition, results demonstrate how early life (larval) exposure to biofouling in the rearing environment may influence fish microbiome development which is important for animal health and aquaculture production.

Spontaneous and Induced Tumors in Germ-Free Animals: A General Review

Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome′s importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.

Weight Shapes the Intestinal Microbiome in Preterm Infants: Results of a Prospective Observational Study

Background: The intestinal microbiome in preterm infants differs markedly from term infants. It is unclear whether the microbiome develops over time according to infant specific factors. Methods: We analysed (clinical) metadata - to identify the main factors influencing the microbiome composition development - and the first meconium and feacal samples til the 4th week via 16S rRNA amplican sequencing. Results: We included 41 infants (gestational age 25-30 weeks; birth weight 430-990g. Birth via Caesarean section (CS) was associated with placental insufficiency during pregnancy and lower BW. In meconium and in weeks 2 and 3 an increased combined abundance of Escherichia and Bacteroides (maternal fecal representatives) was associated with vaginal delivery (p=0.021, p=0.0002, p=0.028, respectively) while Staphylococcus (skin microbiome representative) was associated with CS (p=0.0008, p=0.0003 p=0.046, respectively). Secondly, irrespective of the week of sampling or the mode of birth, a transition was observed as children children gradually increased in weight from a microbiome dominated by Staphylococcus (Bacilli) towards a microbiome dominated by Enterobacteriaceae (Gammaproteobacteria). Conclusions: Mode of delivery affects the meconium microbiome composition. It also suggests that the weight of the infant at the time of sampling is a better predictor for the stage of progression of the intestinal microbiome development/maturation than postconceptional age.