Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Microbiome-based intervention strategies for childhood pneumonia. (93954)

Ritika K Bahal 1 , Luke Garratt 2 3 , Daniel Laucirica 2 3 , Kan Yu 1 , Anthony Kicic 2 3 , Mark P Nicol 1
  1. School of Biomedical Sciences, University of Western Australia, Nedlands, Western Australia, Australia
  2. Telethon Kids Institute, Nedlands, WA, Australia
  3. UWA Medical School, The University of Western Australia Centre for Child Health Research, Crawley, WA, Australia

Pneumonia or lower respiratory tract infection (LRTI) remains the leading cause of child death outside of the neonatal period, worldwide. The nasopharynx is a reservoir for microbes that may cause life-threatening pneumonia in children. Vaccines have been effective in preventing severe bacterial LRTI, however they are serotype-specific and a recent study identified that bacterial pathogens still cause a substantial proportion of LRTI in children1. Opportunistic pathogens such as Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) commonly reside in the nasopharynx of children. We studied the composition of nasopharyngeal microbiome during LRTI in comparison with age-matched healthy controls in infants enrolled in a South African birth cohort2. NTHi was strongly associated with LRTI in children <2 years of age. Interestingly, absence of health-promoting commensal bacteria Dolosigranulum and Corynebacterium was associated with severe disease, while their relative abundance was negatively associated with abundance of NTHi. However, our sequence-based microbiome analysis was only able to assign taxonomy at the genus level. In this work, we leveraged on these findings to identify commensal bacterial strains associated with reduced LRTI susceptibility.

We hypothesized that acquisition of Corynebacterium and Dolosigranulum species either alone or together protect against colonization by NTHi. We created a biobank of commensal isolates obtained from different healthy individuals from our cohort. We investigated the inhibition of NTHi by strains of different species of Corynebacterium and Dolosigranulum using in vitro bacterial-bacterial interaction assays. We have identified the commensal nasopharyngeal bacterial species that inhibit NTHi, and that this inhibition is likely due to the production of soluble molecules. To understand the biomechanisms of interaction in relation to their physiological location, we have also established week-long infection model of primary nasal epithelial cells cultured at Air-Liquid Interphase (ALI). This model will be used to further investigate interactions between reduced complexity communities and the respiratory mucosa.

This research directly contributes to our understanding of the role the microbial ecology in pathogenesis of respiratory infections. The overarching vision is that the microbial biomarkers of protection against LRTI identified through our research will serve as targets for novel intervention strategies such as development of a new probiotic product.

  1. Pneumonia Etiology Research for Child Health Study, G., Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet, 2019. 394(10200): p. 757-779.
  2. Zar HJ, Barnett W, Stadler A, Gardner-Lubbe S, Myer L, Nicol MP. Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study. Lancet Respir Med. 2016;4(6):463-72.