Doctoral Degrees (Medical Microbiology)

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Browsing Doctoral Degrees (Medical Microbiology) by Author "Van Zyl, Kristien Nel"

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    Exploring the gut microbiome of children from Cape Town communities
    (Stellenbosch : Stellenbosch University, 2021-12) Van Zyl, Kristien Nel; Newton-Foot, Mae; Whitelaw, Andrew Christopher; Stellenbosch University. Faculty of Science. Dept. Department of Pathology. Medical Microbiology.
    ENGLISH ABSTRACT: Despite the increase in microbiome investigations in the last decade, descriptions of the microbiota remain limited in developing countries, particularly in children. Little is known about the gut microbiota of young children in South Africa and there is a need for investigations of the composition and diversity of microbiota and the influence of demographic, clinical, and environmental factors on the microbiota in this setting. This study formed part of the ongoing Tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) clinical trial, which aims to determine the efficacy and safety of levofloxacin preventive therapy in a cohort of children <5 years exposed to multidrug-resistant tuberculosis in the household. This sub-study explored the composition, diversity, and factors influencing the baseline bacterial and fungal gut microbiota of these children, prior to randomisation into treatment or placebo arms. A pilot study was performed to assess the effect of stool sample storage and transport conditions on the microbiota and to develop a practical DNA extraction standard operating procedure for the remainder of the sub-study and future microbiome studies in this setting. Quantitative PCR showed that the gut microbiota was not affected by storage and transport conditions common to this setting. Targeted 16S rRNA and internal transcribed spacer 1 gene sequencing was performed on the Illumina platform to characterise the bacterial and fungal microbiota. The bacterial microbiota of young children from Cape Town communities were shown to be similar to those in children from developing countries and age was the main driver of differences in both bacterial and fungal communities. While the risk for dysbiosis was shown to be low overall, recent antibiotic use and household pollution were associated with reduced bacterial diversity. The inconsistent detection and abundance of fungi even in participants of the same age, highlighted the need for expanded research, including dietary and longitudinal analysis. The need for longitudinal analysis in paediatric populations was further emphasised by a systematic review on the effects of antibiotics on the microbiome, particularly in populations who are at risk for increased antibiotic exposure. The findings also demonstrated the population and target site-specific responses of the microbiome to antibiotics, which underlined the need for individual evaluation of the effect of antibiotics on the gut microbiome. This study set the groundwork for future investigations in the TB-CHAMP cohort, including the temporal development and stability of the gut microbiome in these children, and the impact of levofioxacin preventive therapy on the microbiota and resistance reservoirs in the gut.