Browsing by Author "Tow, Lemese Ah"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Open Access
    Association of Faecalibacterium, Lachnospira, Veillonella, and Rothia with childhood wheezing
    (2019) Kanyemba, Saara; Kaba, Mamadou; Tow, Lemese Ah
    Wheezing symptoms among children, present major health and economic problems globally. A recent study conducted in Canada observed a reduction in stool bacterial genera Faecalibacterium, Lachnospira, Veillonella and Rothia (FLVR) in three-month old infants with atopy-wheeze symptoms. It is not known whether this is true in different human populations worldwide. The overall aim of this dissertation was to investigate the contribution of any of the FLVR bacteria or their combination in the occurrence of infant wheezing within the Drakenstein Child Health Study (DCHS), South Africa. To address this aim, I began my thesis's project by conducting a systematic literature review which investigated the association of FLVR bacteria with the occurrence of different respiratory diseases in humans. My review provided evidence for the possible involvement of FLVR bacteria in human respiratory diseases, including asthma, pulmonary tuberculosis and pneumonia. Furthermore, this review highlighted the need for a well-designed and large study to investigate the contribution of the FLVR bacteria in respiratory diseases, in an African setting. Secondly, I optimized SYBR Green based real-time quantitative polymerase chain reaction (qPCR) as well as conventional PCR assays for the detection of FLVR bacteria. Using the optimized assays, I screened 533 stool samples collected from 140 wheezing and 140 nonwheezing infants. The optimized assays demonstrated good performance in the detection of FLVR bacteria from human stool samples. Using qPCR, Rothia, Veillonella, Faecalibacterium and Lachnospira were detected in 90% (479/533), 73% (388/533), 51% (274/533) and 14% (77/533) of the samples, respectively. Conventional PCR permitted the detection of Rothia, Veillonella, Faecalibacterium and Lachnospira in 55% (263/479), 74% (289/388), 53% (145/274) and 0% (0/77) of the qPCR positive samples, respectively. I also determined the factors associated with faecal colonization by FLVR bacteria in the first year of life. I showed that reduced colonisation by Faecalibacterium was associated with male gender (adjusted OR = 0.65, 95%CI: 0.42 - 0.98) and TC-Newman residence (adjusted OR = 0.52, 95%CI: 0.29 - 0.91). Breastfeeding was associated with less colonisation by both Lachnospira, (adjusted OR = 0.17, 95%CI: 0.05 - 0.49) and Veilonella (adjusted OR = 0.32, 95%CI: 0.10 - 0.91). Mother's tertiary education was significantly associated with high Rothia colonisation (adjusted OR = 11.73, 95%CI: 1.36 - 2.58). In the last section of my thesis, I assessed the association of FLVR bacteria with infant wheezing using logistic regression models. I found a significant association of Rothia with reduced risk of infant wheezing (adjusted odds ratio (aOR)=0.54, 95%CI: 0.28-0.93) and recurrent wheezing (aOR=0.29, 95%CI: 0.05-0.88). Using receiver operating characteristic curves (ROC), I showed that among all FLVR bacteria, Lachnospira (AUROC = 0.833, 95%CI: 0.64-1.00) and Rothia (AUC=0.707, 95%CI: 0.62-0.79) could serve as biomarkers for early prediction of infant wheezing. Overall, this is the first study on FLVR bacteria and infant wheezing to be conducted in Africa. Its findings encourage more research to be conducted in order to elucidate the potential protective role of Rothia against childhood wheeze and asthma, as well as the contribution of Lachnospira in asthma development.
  • Thumbnail Image
    Item
    Open Access
    The stool microbiota and infant wheezing illness - the Drakenstein child health study, South Africa
    (2019) Ngwarai, Michelle Rudo; Kaba, Mamadou; Tow, Lemese Ah
    Background: Wheezing is one of the leading respiratory symptoms in childhood, which with recurrent occurrence can lead to asthma at school age. Few studies, with conflicting findings, have investigated the contribution of stool bacteria in childhood wheezing illness. Additionally, most of the published studies were conducted in high-income countries using small sample sizes and targeted bacterial detection techniques. To address these limitations, we conducted this study to determine the association of the infant stool bacterial diversity and composition with wheezing development. Methods: We conducted a longitudinal case-control study nested within the Drakenstein Child Health Study, Western Cape, South Africa. We included 140 infants with wheeze (cases) and 140 age-matched controls. Passed faecal samples were collected from infants at birth, whilst aspirated or passed faecal samples were collected at six weeks, six months and 12 months. Deoxyribonucleic acid (DNA) was extracted from all the samples using the manual ZR Fecal DNA MiniPrep™ Kit. Sequencing of the hypervariable V4 region of the 16S rRNA gene was performed using the Illumina MiSeq technique. The resulting sequencing data was subjected to bioinformatic quality control checks and statistical analysis. Results: One of the main findings from the systematic review of wheezing data was the observed association between the development of atopic wheezing and four bacteria namely Faecalibacterium, Lachnospira, Veillonella and Rothia. This study included 280 children (n=123 female and n=157 male) recruited from TC Newman (38.5%) and Mbekweni (61.5%) areas. Stool samples were collected from 159 infants at birth, 114 infants at six weeks, 141 infants at six months and 98 infants at 12 months of age. Aspirate and passed stool samples were found to be similar and comparable in terms of the bacterial composition. At age six weeks, 16% (23/140) of the infants included had wheezed once. During the first year, the proportion of infants with recurrent wheezing (≥ 2 wheezing episodes) was 56% (78/140). Independent factors influencing the composition and diversity of the infants faecal bacteria were feeding practices, age of mothers and living conditions (all p0.05). In addition, we did not find significant difference between infants with and without wheeze for selected bacteria reported to be associated with wheezing. However, we observed an increased relative abundance of Proteobacteria at 12 months of age in infants who had previously wheezed. Additionally, Lactobacillales was in apparently significantly higher proportions in recurrent wheezers as compared to infants who wheezed once (p< 0.05). We did not observe distinct faecal bacterial profiles between infants with and without wheeze at any taxonomic level analysis (all p> 0.05). In addition, we did not find significant difference between infants with and without wheeze for selected bacteria reported to be associated with wheezing. However, we observed an increased relative abundance of Proteobacteria at 12 months of age in infants who had previously wheezed. Additionally, Lactobacillales was in apparently significantly higher proportions in recurrent wheezers as compared to infants who wheezed once (p< 0.05). Conclusion: This study shows that aspirated stool is a good alternative for passed stool in microbiome studies. Furthermore, it revealed the complex and dynamic nature of the faecal bacteria, as well as factors influencing the faecal bacterial profile during the first year of life. More studies in this cohort, including the use of metagenomic and metabolomic approaches are required to demonstrate the role played by bacterial types and their metabolites in the development of wheezing illness. Finally, because recurrent wheezing is one of the precursors of asthma, there is a need for an additional follow-up of these infants in order to investigate the contribution of the early faecal microbiome in the development of asthma at school age.