Microbial colonization of mucosal tissues during infancy plays an instrumental role in the development and education of the host mammalian immune system. These early-life events can have long-standing consequences: facilitating tolerance to environmental exposures or contributing to the development of disease in later life, including inflammatory bowel disease, allergy, and asthma. Recent studies have begun to define a critical period during early development in which disruption of optimal host-commensal interactions can lead to persistent and in some cases irreversible defects in the development and training of specific immune subsets. Here, we discuss the role of early-life education of the immune system during this “window of opportunity,” when microbial colonization has a potentially critical impact on human health and disease.

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How colonization by microbiota in early life shapes the immune system

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Background: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. Methods: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. Results: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium ) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia–Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. Interpretation: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.

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Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months

To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition has significantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour However, the role of epigenetics in informing host-microbe interactions has received little attention to date This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue From this new perspective we put forward novel, yet testable, hypotheses Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour Secondly, we argue that the microbiota is an important mediator of gene-environment interactions Finally, we reason that the microbiota itself may be viewed as an epigenetic entity In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction

https://onlinelibrary.wiley.com/doi/pdf/10.1111/gbb.12109

Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis.

The human gut is the habitat for diverse and dynamic microbial ecosystem. The human microbiota plays a critical role in functions that sustain health and is a positive asset in host defenses. Establishment of the human intestinal microbiota during infancy may be influenced by multiple factors including delivery mode. Present review compiles existing evidences on the effect of delivery mode on the diversity and colonization pattern of infants gut microbiota. Two investigators searched for relevant scientific publications from four databases (Pubmed, Medline, Embase, and Web of Science). The last search was performed on September 21, 2015, using key terms ((delivery mode OR caesarean delivery OR cesarean section OR vaginal delivery) AND (gut microbiota OR gut microbiome OR gut microflora OR intestinal microflora OR microbial diversity) AND (infants OR children)). All included studies described at least two types of gut microbiota in relation to delivery mode (caesarean section vs vaginal delivery) and used fecal samples to detect gut microbiota. Seven out of 652 retrieved studies met inclusion criteria, were included in systematic analysis. Caesarean Section (CS) was associated with both lower abundance and diversity of the phyala Actinobacteria and Bacteroidetes, and higher abundance and diversity of the phylum Firmicute from birth to 3 months of life. At the colonization level, Bifidobacterium, and Bacteroides genera seems to be significantly more frequent in vaginally delivered infants compared with CS delivered. These infants were more colonized by the Clostridium, and Lactobacillus genera. From the reports, it is tempting to say that delivery mode has less effect on colonization and diversity of Bifidobacteria, Bacteroides, Clostridium, and Lactobacillus genera from the age of 6 to 12 months of life. The diversity and colonization pattern of the gut microbiota were significantly associated to the mode of delivery during the first three months of life, however the observed significant differences disappears after 6 months of infants life. The healthy gut microbiota is considered to promote development and maturation of the immune system while abnormal gut is considered as the major cause of severe gastrointestinal infections during the infancy. Further studies should investigate the diversity and colonization levels of infant gut microbiota in relation to the mode of delivery and its broad impact on infants’ health at each stage of life.

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Jona Rushing

Papers

Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis

Probiotics for pregnant women and preterm neonates.