Changes

The uniqueness of an individual’s microbiota is established during the first few years of life and alterations to the microbiota during this time can have a profound effect on the long-term wellbeing of the individual. Development of the microbiota is characterised by large, rapid changes in microbial populations, diversity and abundance.1 Such changes will occur due to a number of factors in-utero, during the neonatal period, maternal transfer and throughout the weaning process.  

The uniqueness of an individual’s microbiota is established during the first few years of life and alterations to the microbiota during this time can have a profound effect on the long-term wellbeing of the individual. Development of the microbiota is characterised by large, rapid changes in microbial populations, diversity and abundance.<ref>Matamoros S, Gras-Leguen C, Le Vacon F, Potel G, de La Cochetiere, M-F. Development of intestinal microbiota in infants and its impact on health. ''Trends in Microbiology'' 2013; 21(4):167-173</ref> Such changes will occur due to a number of factors in-utero, during the neonatal period, maternal transfer and throughout the weaning process.  

It was originally thought that the foetus developed in a sterile environment within the uterus, with initial microbial exposure occurring extra-uterine during birth. However, studies have demonstrated the presence of bacterial DNA in the placenta and amniotic fluid from healthy term pregnancies, and umbilical cord blood from caesarean delivered neonates.2,3 Furthermore, genetically labelled Enterococcus faecium given to pregnant mice was found in the meconium of their pups, despite delivery by caesarean,4 suggesting that development of the microbiota may begin in-utero via maternal transfer.

It was originally thought that the foetus developed in a sterile environment within the uterus, with initial microbial exposure occurring extra-uterine during birth. However, studies have demonstrated the presence of bacterial DNA in the placenta and amniotic fluid from healthy term pregnancies, and umbilical cord blood from caesarean delivered neonates.<ref>Steel JH, Malatos S, Kennea N, et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. ''Pediatric Research'' 2005; 57(3): 404-411</ref>,<ref>Jiménez E, Fernández L, Marín ML, et al. Isolation of commensal bacteria from umbilical cord  blood of healthy neonates born by cesarean section. ''Current Microbiology'' 2005; 51(4): 270–274</ref> Furthermore, genetically labelled Enterococcus faecium given to pregnant mice was found in the meconium of their pups, despite delivery by caesarean,<ref>Jiménez E, Marín ML, Martín R, et al. Is meconium from healthy newborn actually sterile? ''Research in Microbiology'' 2008; 159(3): 187-193</ref> suggesting that development of the microbiota may begin in-utero via maternal transfer.

Establishment of the skin, oral, nasopharyngeal and gut microbiota in newborns occurs during delivery. As the infant exits the birth canal during vaginal birth, it is covered in vaginal and faecal bacteria, acquiring a microbiota similar to that of the vagina. Whereas caesarean section delivered newborns develop a microbiota more similar to the skin.5 Importantly, newborn canines can be exposed to the mother’s vaginal and faecal microbiota through the mother’s tongue, thus the effect of delivery mode may be less pronounced compared to humans.6

Establishment of the skin, oral, nasopharyngeal and gut microbiota in newborns occurs during delivery. As the infant exits the birth canal during vaginal birth, it is covered in vaginal and faecal bacteria, acquiring a microbiota similar to that of the vagina. Whereas caesarean section delivered newborns develop a microbiota more similar to the skin.<ref>Dominguez-Bello MG, Costello EK, Contreras M et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. ''Proceedings of the National Academy of Sciences of the United States of America'' 2010; 107(26): 11971-11975</ref> Importantly, newborn canines can be exposed to the mother’s vaginal and faecal microbiota through the mother’s tongue, thus the effect of delivery mode may be less pronounced compared to humans.<ref name=":0">Pilla R, Suchodolski JS. The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. ''Frontiers in Veterinary Science'' 2020; 14(6):498 </ref>

Maternal transfer via breastfeeding plays an important role in developing the neonatal gut microbiota post-partum. This occurs directly through exposure to milk microbiota which contains hundreds of bacterial species and indirectly, via maternal milk; factors such as oligosaccharides, secretory IgA and anti-microbials can affect bacterial numbers and activity.7 Unsurprisingly, the microbiota from breastfed-infants differs significantly to formula-fed infants due to microbial contents of the milk.8

Maternal transfer via breastfeeding plays an important role in developing the neonatal gut microbiota post-partum. This occurs directly through exposure to milk microbiota which contains hundreds of bacterial species and indirectly, via maternal milk; factors such as oligosaccharides, secretory IgA and anti-microbials can affect bacterial numbers and activity.<ref>van den Elsen LWJ, Garssen J, Burcelin R, Verhasselt V. Shaping the Gut Microbiota by Breastfeeding: The Gateway to Allergy Prevention? ''Frontiers in Pediatrics'' 2019; 7:47</ref> Unsurprisingly, the microbiota from breastfed-infants differs significantly to formula-fed infants due to microbial contents of the milk.<ref name=":1">Di Mauro A, Neu J, Riezzo G, Raimondi F, Martinelli D, Francavilla R, Indrio F. Gastrointestinal function development and microbiota, ''Italian    Journal of Pediatrics'' 2013; 39(1):15</ref>

The maturation of the microbiota into an adult-like composition occurs throughout the weaning process. Puppies tend to have variable microbiota compositions whereas healthy adults have a much more stable microbiota.6 Variations in diet composition can also have dramatic effects on the microbiota. For example, macronutrient differences in carnivorous verses herbivorous diets will be reflected in gut microbiota composition.6 Alterations to the microbiota can also occur following infections or illnesses, environmental or dietary change or exposure to certain medications and supplements, such as antibiotics and probiotics.9,10

The maturation of the microbiota into an adult-like composition occurs throughout the weaning process. Puppies tend to have variable microbiota compositions whereas healthy adults have a much more stable microbiota.<ref name=":0" /> Variations in diet composition can also have dramatic effects on the microbiota. For example, macronutrient differences in carnivorous verses herbivorous diets will be reflected in gut microbiota composition.<ref name=":0" /> Alterations to the microbiota can also occur following infections or illnesses, environmental or dietary change or exposure to certain medications and supplements, such as antibiotics and probiotics.<ref>David LA, Maurice CF, Carmody RN et al. Diet rapidly and reproducibly alters the human gut microbiome. ''Nature'' 2014; 505(7484): 559-563</ref>,<ref>Cho I, Yamanishi S, Cox L et al. Antibiotics in early life alter    the murine colonic microbiome and adiposity. ''Nature'' 2012; 488(7413):    621-626</ref>

The microbiota plays a crucial role in normal gastrointestinal structural development via direct interactions with immune cells, mucosal cells and neuronal endings.8 This has been studied in rodents where antibiotic administration in rats at the end of gestation resulted in pups with small stomachs, reduced acid secretion and increased intestinal permeability.11 While germ free mice have been shown to develop a greatly enlarged caecum, reduced intestinal surface area, decreased epithelial cell turnover, smaller Peyer’s Patches and disordered gut-associated lymphoid tissue and smaller villous thickness.8 This suggests that a healthy microbiota in neonates may be vital for the normal development of the structural intestinal mucosa, gastrointestinal mucosal immunity and gastrointestinal functions.  

The microbiota plays a crucial role in normal gastrointestinal structural development via direct interactions with immune cells, mucosal cells and neuronal endings.<ref name=":1" /> This has been studied in rodents where antibiotic administration in rats at the end of gestation resulted in pups with small stomachs, reduced acid secretion and increased intestinal permeability.<ref>Fåk F, Ahrné S, Molin G, Jeppsson B, Weström B. Microbial    manipulation of the rat dam changes bacterial colonization and alters    properties of the gut in her offspring. ''American Journal of    Physiology-Gastrointestinal and Liver Physiology'' 2008; 294(1):    G148–154</ref> While germ free mice have been shown to develop a greatly enlarged caecum, reduced intestinal surface area, decreased epithelial cell turnover, smaller Peyer’s Patches and disordered gut-associated lymphoid tissue and smaller villous thickness.<ref name=":1" /> This suggests that a healthy microbiota in neonates may be vital for the normal development of the structural intestinal mucosa, gastrointestinal mucosal immunity and gastrointestinal functions.  

Research is ongoing in the development of the microbiota through using DNA-based detection techniques to identify specific bacterial species involved. Epidemiological studies in humans have linked disruptions within the neonatal microbiota to immune-mediated diseases such as inflammatory bowel disease (IBD), allergic rhinitis and atopic dermatitis12 With further research, we may be able to optimise this critical period in microbiota development to reduce the incidence of these diseases, not only in humans, but also in canines and felines.

Research is ongoing in the development of the microbiota through using DNA-based detection techniques to identify specific bacterial species involved. Epidemiological studies in humans have linked disruptions within the neonatal microbiota to immune-mediated diseases such as inflammatory bowel disease (IBD), allergic rhinitis and atopic dermatitis<ref>Conroy ME, Shi HN, Walker WA. The long-term health effects of neonatal microbial flora. ''Current Opinion in Allergy & Clinical Immunology'' 2009; 9(3): 197-201</ref> With further research, we may be able to optimise this critical period in microbiota development to reduce the incidence of these diseases, not only in humans, but also in canines and felines.

Author: Benjamin Sofaer BVSc, Veterinary Territory Manager at Protexin Veterinary. Protexin Veterinary is a brand of ADM Protexin Ltd

 

'''Author: Benjamin Sofaer BVSc, Veterinary Territory Manager at Protexin Veterinary. Protexin Veterinary is a brand of ADM Protexin Ltd'''