1. Factors influencing the microbiome in early life
Dr Waceke Kombe
Paediatric Gastroenterologist

2. Outline Factors to be discussed Mode of delivery Prematurity
Exclusive breastfeeding
Introduction of complimentary foods
Early life antibiotic exposures
Summary and conclusion.

3. Mode of delivery.
Mode of delivery has a huge influence on early-life microbiome.
Vaginally delivered infants become acutely colonized with intestinal organisms that reflect the mother’s vaginal tract ( Lactobacillus, Prevotella, Sneathia)
Infants delivered by caesarian section become colonized by intestinal organisms reflective of the maternal skin (Staphylococcus, Propionibacterium and Cornynebacterium) 1.
These changes have been observed to last as long as 7 years.

4. Mode of delivery
The deficits in the human microbiome associated with C-section have been implicated in certain autoimmune diseases , celiac disease, asthma and type 1 diabetes. 1
Trials are ongoing on vaginal seeding. Vaginal fluids are applied to newborn child delivered by C-section in efforts to restore the human microbiome.

5. Prematurity
 Fecal microbiota of premature infants is different from that of term infants and their gut colonization is delayed and aberrant.
It is generally characterized by
lower diversity
more fluctuations
Higher representation of potential pathogenic microorganisms typically encountered in hospital environments
Reduced representation of health-related commensal microorganisms.2

6. Prematurity
In preterm infants , up to 3 weeks before NEC diagnosis, gut microbiota shifts toward an increased presence of potential pathogens.
These include   Corynebacterium,  Klebsiella, Clostridium, or Enterobacter species. 2
This opens new avenues to identify markers of NEC that would aid in the establishment of early therapeutic approaches.

7. FIGURE 2
Perinatal Microbiomes’ Influence on Preterm Birth and Preterms’ Health: Influencing Factors and Modulation Strategies
Ruiz, Lorena; Moles, Laura; Gueimonde, Miguel; Rodriguez, Juan M.
Journal of Pediatric Gastroenterology and Nutrition63(6):e193-e203, December 2016.
doi: /MPG
General overview of environmental factors that may condition microbiomes at perinatal stages of life, including maternal factors during pregnancy (A), post partum (B), and hospital-related factors known to affect microbiomes establishment in neonates during early weeks of life (C). Stages in which dietary strategies, including probiotics and prebiotics, are feasible for microbiomes modulation are indicated with a star. HPA = hypothalamic-pituitary- adrenal; NEC = necrotizing enterocolitis; NICU = neonatal intensive care unit.
Copyright © 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

8. BREASTFEEDING AND THE MICROBIOME
Exclusively breastfeeding results in high levels of bifidobacterium and lactobacillus species. Human milk contains prebiotics such as oligosaccharides that promote the growth of these key communities3,4.
These organisms:
Inhibit the growth of pathogenic bacteria.
Improve barrier function in the infant gut by tightening cellular junctions and expressing antimicrobial peptides.

9. BREASTFEEDING AND THE MICROBIOME
There is a difference in composition of the microbiome in infants who are breastfed versus those who are formula fed.
Breastfed infants- higher proportion of bifidobacterium and lactobacillus.
Formula fed infants- higher proportion of clostridiales and proteobacteria.

11. Exclusive and partial formula-feeding have been shown to alter the gut microbiome toward adult patterns, increase proinflammatory bacterial taxa, increase gut permeability, and result in lower concentrations of fecal short-chain fatty acids.

12. Introduction of complimentary foods
Introduction of solid food and the cessation of breastfeeding increases adult-associated microbes, such as Lachnospiracus and Ruminococcacus.
It also reduces presence of Lactobacillacus, Bifidobacteria and Enterobacteria. 5
This transition is necessary and beneficial. It allows for a microbial community that is better equipped to extract energy and process a diet that is similar to the diet of a mature adult.6

13. Use of antibiotics
The effect on the microbiome secondary to use of an antibiotic is transcient.
It is best highlighted by the research regarding Clostridium difficile.
Fecal microbiota transplantation has been shown to be effective and safe in treatment of Clostridium difficile. 7

14. Use of antibiotics
Antibiotics use significantly diminished phylogenetic diversity immediately after birth. (p<0.0001), but diversity recovered during infancy. 8
Children exposed to antibiotics showed delayed microbiota maturity.

15. Fig. 2. α-Diversity during the first 2 years of life in relation to antibiotic treatment, delivery mode, and predominant diet.
α-Diversity during the first 2 years of life in relation to antibiotic treatment, delivery mode, and predominant diet. (A to I) Left: Mean phylogenetic diversity ± SEM. Middle: Mean observed OTUs ± SEM. Right: Mean Shannon equitability (evenness) ± SEM. α-Diversity is shown for antibiotic use (A to C), delivery mode (D to F), and diet (G to I). Asterisks indicate significant linear longitudinal model (LLM) (P < 0.05) group differences at baseline or rate-of-change differences across age ranges (dotted lines demarcate time periods tested).
Nicholas A. Bokulich et al., Sci Transl Med 2016;8:343ra82
Published by AAAS

16. Summary and conclusion.
The factors studied ALL affect the gut microbiome.
Clinical applications include prevention from certain diseases and use of modalities such as fecal microbial transplant.

17. REFERENCES
Rudolf S, Kunz C. Milk oligosaccharides and metabolism in infants. Adv Nutri 2012; 3: 398S-405S.
Coppa GV, Bruni S, Morelli L, et al. The first prebiotics in humans: human milk oligosaccharides. J. Clin Gastroenterol 2004; 38 (Suppl 6) S80-S83.
Salminen S, Gibson GR, McCartney AL, et al. Influence of mode of delivery on gut microbiota composition in seven year old children. Gut 2004; 53:

18. REFERENCES
4. Ruiz L, Laura M, Guenimonde M et al, Perinatal Microbiomes’ influence on preterm birth and preterms’ health: Influencing factors and modulation strategies. JPGN 2016; 63:e193-e203.
5. Bergstrom A, Skov TH, Bahl MI et al. Establishment of microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol 2014; 80:
6. Dong T S, Gupta A. Influence of Early life, Diet, and the Enviroment on the Microbiome. Clin Gastroenterol Hepatol 2019; 17:

19. REFERENCES
7. Gianotti RJ, Moss AC. Fecal microbiota transplantation: from Clostridium difficile to inflammatory bowel disease. Gastroenterol Hepatol (N Y) 2017;13: Bokulich NA, Chung J, Battaglia T et al. Antibiotics, birth mode and diet shape microbiome maturation during early life. Sci Transl Med 2016; 8:343ra82.