The effect of weaning food substrate on segmented filamentous bacteria in infant small intestinal immune barrier maturation : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutrition at Massey University, Palmerston North, New Zealand (School of Food and Advanced Technology)

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Appropriate and complete maturation of the gastrointestinal tract (GIT) barriers is crucial as it contributes to overall health and wellness. Maturation of the small intestinal immunological barrier has gained interest due to GIT-associated disorders such as inflammatory bowel disease thought to be caused by improper maturation. The transition from milk-based feeding to complementary feeding in healthy infants at weaning introduces new antigens and microbes into the GIT. These changes induce immune cell production and is thought to be the final stages in the maturation process of the immunological barrier. It is during this maturation process at weaning that segmented filamentous bacteria (SFB) are thought to play a role. These Gram-positive, obligate anaerobic, spore-forming commensals have been observed in the faeces of 6–25-month-old infants and the terminal ileum of weanling rodents. The abundance of ileal and faecal SFB increases at weaning, peaks then decreases post-weaning and remains at that lower plateau throughout life. The transient abundance change of SFB has also been correlated with immune markers, immunoglobulin A (IgA) concentration in faeces and interleukin 17 (IL-17) concentration in blood plasma. The reported correlation between SFB, IgA and IL-17, and the timing at which the abundance of SFB changes at weaning, suggests that weaning foods might have an influence on changes in SFB abundance and hence on the immunological barrier. The published SFB genome identified carbohydrate metabolic and transport genes and a published study also reported an influence of complex substrates from the diet on SFB abundance. These findings suggested that a diet supplemented with complex carbohydrates may enhance the ileal SFB abundance, which had not been investigated at weaning previously. The aim therefore of this thesis was to investigate whether the complex carbohydrate inulin would influence the ileal and faecal abundances of SFB at weaning and would modulate the concentration of the GIT immune markers, IgA in faeces, and IL-17 in plasma. The hypothesis was that a weaning diet enriched with inulin would increase the peak abundance of SFB in the terminal ileum which would then enhance GIT immune barrier maturation. Initial method development showed that the temporal profile of SFB colonisation in the ileal tissue and contents of weanling rats was similar to those published for mice and infants of corresponding weaning age. Additionally, and for the first time, whole tissue homogenisation was favoured over ileal mucosal scraping as the ideal collection technique due to lower variability in whole ileal tissue data. These methods were implemented in a final study where inulin was selected because it is commonly found in weaning foods such as fruit and vegetables and is also routinely added to bovine-based milk formulas to supplement the deficit of oligosaccharides (compared to human milk). Results revealed that inulin did not influence the peak abundance of SFB, regardless of inulin dosing (0%, 2.5%, 5%, 10%) or sample type (ileal tissue, ileal contents, faeces), three days post-weaning in 24-day-old Sprague-Dawley rats. There were no differences of inulin dosing on ileal and faecal SFB abundances, blood plasma IL-17 and faecal IgA concentrations, nor between male and female rats. This outcome from the inulin intervention suggests that SFB may not utilise inulin directly or a longer period of adaptation to the inulin-supplemented diet might be required to assess if there is a long-term effect on ileal SFB abundance. The findings do not rule out other complex carbohydrates with potential influence on ileal SFB abundance. Further investigation would entail determining any interactive effects among inulin-supplemented diet, SFB abundance, and immune markers at broader time-points beyond the expected peak of SFB abundance post-weaning. In addition, analysis could be carried out to determine the abundance of other microbes relative to the predicted pre- and post-weaning SFB abundance changes. Further investigations will advance our understanding on the ability of specific food substrates to manipulate SFB and important members of the GIT microbiota and in turn support the development of high-value foods for overall health benefits in infants.
The articles in Appendix V are © Authors and re-published under a CC BY 4.0 license: Oemcke, LA, Anderson, RC, Altermann, E, Roy, NC and McNabb, WC. (2021) The role of segmented filamentous bacteria in immune barrier maturation of the small intestine at weaning. Frontiers in Nutrition (doi: 10.3389/fnut.2021.759137). Oemcke, LA, Anderson, RC, Rakonjac, J, McNabb, WC, & Roy, NC. (2021) Whole tissue homogenization preferable to mucosal scraping in determining the temporal profile of segmented filamentous bacteria in the ileum of weanling rats. Access Microbiology (doi: 10.1099/acmi.0.000218).
Immune system, Infants, Weaning, Intestines, Microbiology, Inulin