Changes in the human microbiome among community-based individuals experiencing respiratory tract infection: exploratory analysis of a feasibility cohort study.

Conference:

SAPC ASM 2021 - virtual

Talk Code:

P1.21.1

Presenter:

Claire A Woodall

Twitter:

@ClaireWoodall

Co-authors:

Claire A. Woodall1, Ashley Hammond1, Peter Muir2, Ben Pascoe3, Sam Sheppard3, Andy Preston3 and Alastair D. Hay1.

Author institutions:

1Centre for Academic Primary Care, Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK. 2Public Health England, South West Regional Laboratory, National Infection Service, Southmead Hospital, Bristol, BS10 5NB, UK. 3The Milner Centre for Evolution and Department of Biology and Biochemistry, University of Bath, Bath, UK.

Problem

There are a distinct lack of studies tracking microbial provenance during an RTI episode. Our longitudinal feasibility study was designed to address this lack of evidence by recruiting community-based individuals with an RTI and identify microbial patterns before, during, and after the RTI episode and also to reveal microbial biomarkers suggestive of susceptibility to RTI acquisition.

Approach

Adults were recruited between October 2019 and March 2020 and stool and saliva samples were collected from participants, as a proxy for gut and upper respiratory tract, respectively. Participants reported RTI symptoms (RTI-S) and collected samples at three time points: (As) pre-RTI, (B) during-RTI and (Cs) post-RTI. Whereas those with no RTI symptoms (non-RTI) collected samples at two time points: (An) pre-RTI and (Cn) post-RTI. Bacterial genomic DNA was extracted, amplified and the 16S rRNA gene was sequenced. Taxonomic and statistical analysis was performed using QIIME2 and R. Reverse transcriptase (RT)-PCR was used to detect respiratory pathogen gene targets including the SARS-CoV-2 virus. Covariate demographic, characteristic and PCR data were cross-tabulated with the associated microbial profile.

Findings

In total, 19 and 28 participants reported RTI-S and non-RTI, respectively. The mean age of RTI-S participants was 46.1 years and 74% were female. Non-RTI participants had a mean age of 48.3 years and 50% were female. A total of 104 stool and 104 saliva samples were analysed. We compared microbiome diversity between As and An (Shannon alpha diversity index, p = 7.17 x 10-8) and between; A to B (p = 3.18 x 10-2), B to C (p = 2.50 x 10-6), A to C (p = 2.96 x 10-6) also in saliva samples between coagulase-negative Staphylococcus sp., (CoNS) positive vs CoNS negative (p = 0.0012). All samples were negative for coronavirus Beta-Cov, E and SARS-CoV-2, S genes. In RTI-S and non-RTI saliva at time-points As and Cs, 73.7%, 57.1% and 76.5%, 47.6% were PCR positive for CoNS respectively and RTI-S saliva at time point B, 84.2% were positive for CoNS.

Consequences

Our feasibility study has demonstrated successful recruitment of participants and collection of samples despite Covid-19 disruptions. Preliminary longitudinal microbiome data highlights dynamic microbial dysbiosis that occurs in the gut and oral cavity during an RTI. Further research is necessary to understand causal pathways.

Submitted by:

Claire Woodall

Funding acknowledgement:

This work was supported by in part the Medical Research Council and Wellcome Trust Institutional Strategic Support Fund (WT ISSF), awarded to CAW on a Daphne Jackson Trust Development Fellow in collaboration with the Elizabeth Blackwell Institute at the University of Bristol. The WT ISSF3 grant number is 204813/Z/16/Z.