Development of the Microbiota

Development of the Microbiota

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.

Foetal Microbiota

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.

Establishment of the Microbiota

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]

Maternal Transfer of the Microbiota

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]

Maturation and Alteration of the Microbiota

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 versus 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]

Gastrointestinal Structural Development

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.

Further Research into the Microbiota

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[12] 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.

In Partnership With Protexin Veterinary


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

www.protexinvet.com

References

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  2. 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
  3. 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
  4. Jiménez E, Marín ML, Martín R, et al. Is meconium from healthy newborn actually sterile? Research in Microbiology 2008; 159(3): 187-193
  5. 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
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  7. 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
  8. 8.0 8.1 8.2 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
  9. David LA, Maurice CF, Carmody RN et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505(7484): 559-563
  10. 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
  11. 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
  12. 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