Oral and gut microbial biomarkers of susceptibility to respiratory tract infection in adults: A feasibility study

We conducted a feasibility cohort study which aimed to recruit and retain adults from the community to collect saliva (oral) and stool (gut) samples at three time points, at the start of the study (baseline), during a respiratory tract infection (RTI) and post-RTI. Community RTIs place a huge burden on health care services, and a non-invasive microbial diagnostic tool to predict the most vulnerable to respiratory infection would be ideal. To this aim, we analysed oral-gut baseline samples comparing those who reported RTI symptoms to those who remained healthy throughout the study for microbial biomarkers of respiratory susceptibility. Amplicon sequence variants (ASV) were identified by 16S sequence profiling to reveal oral-gut microbes. Reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to target common respiratory microbes. Two general practices were recruited, and the participant recruitment rate was 1.3%. A total of 40 adult participants were retained, of which 19 acquired an RTI whereas 21 remained healthy. In healthy baseline oral and gut samples, ASVs from participants with RTI symptoms compared to those who remained healthy were similar with a high relative abundance of Streptococcus sp., and Blautia sp., respectively. Linear discriminant analysis effect size (LEfSe) revealed baseline oral microbes differed, indicating participants who suffered RTI symptoms had enhanced Streptococcus sobrinus and Megamonas sp., and depletion of Lactobacillus salivarius, Synergistetes, Verrucomicrobia and Dethiosulfovibrio. Furthermore, a random forest model ranked Streptococcus (4.13) as the highest mean decrease in accuracy (MDA) and RT-PCR showed a higher level of carriage of coagulase-negative Staphylococcus. Baseline core gut microbes were similar in both participant groups whereas LEfSe analysis revealed enhanced Veillonella, Rikenellaceae, Enhydobacteria, Eggerthella and Xanthomonsdales and depleted Desulfobulbus and Coprobacillus. Sutterella (4.73) had a high MDA value. Overall, we demonstrated the feasibility of recruiting and retaining adult participants from the community to provide multiple biological samples for microbial profiling. Our analyses identified potential oral-gut microbial biomarkers of respiratory infection susceptibility in otherwise healthy participants.