AUTHOR=Li Chengxin , Song Jing , Chen Qihong , Ge Dandan , Li Qiyuan , Yang Yungang 

TITLE=Whole-genome shotgun sequencing unravels the influence of environmental microbial co-infections on the treatment efficacy for severe pediatric infectious diseases

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1308871

DOI=10.3389/fmicb.2024.1308871

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Background</title><p>The microbiome plays a pivotal role in mediating immune deviation during the development of early-life viral infections. Recurrent infections in children are considered a risk factor for disease development. This study delves into the metagenomics of the microbiome in children suffering from severe infections, seeking to identify potential sources of these infections.</p></sec><sec id="sec2"><title>Aims</title><p>The aim of this study was to identify the specific microorganisms and factors that significantly influence the treatment duration in patients suffering from severe infections. We sought to understand how these microbial communities and other variables may affect the treatment duration and the use of antibiotics of these patients with severe infections.</p></sec><sec id="sec3"><title>Method</title><p>Whole-genome shotgun sequencing was conducted on samples collected from children aged 0–14 years with severe infections, admitted to the Pediatrics Department of Xiamen First Hospital. The Kraken2 algorithm was used for taxonomic identification from sequence reads, and linear mixed models were employed to identify significant microorganisms influencing treatment duration. <italic>Colwellia</italic>, <italic>Cryptococcus</italic>, and <italic>Citrobacter</italic> were found to significantly correlate with the duration of clinical treatment. Further analysis using propensity score matching (PSM) and rank-sum test identified clinical indicators significantly associated with the presence of these microorganisms.</p></sec><sec id="sec4"><title>Results</title><p>Using a linear mixed model after removed the outliers, we identified that the abundance of <italic>Colwellia</italic>, <italic>Cryptococcus</italic>, and <italic>Citrobacter</italic> significantly influences the treatment duration. The presence of these microorganisms is associated with a longer treatment duration for patients. Furthermore, these microorganisms were found to impact various clinical measures. Notably, an increase in hospitalization durations and medication costs was observed in patients with these microorganisms. In patients with <italic>Colwellia</italic>, <italic>Cryptococcus</italic>, and <italic>Citrobacter</italic>, we discover significant differences in platelets levels. We also find that in patients with <italic>Cryptococcus</italic>, white blood cells, hemoglobin, and neutrophils levels are lower.</p></sec><sec id="sec5"><title>Conclusion</title><p>These findings suggest that <italic>Colwellia, Cryptococcus</italic>, and <italic>Citrobacter</italic>, particularly <italic>Cryptococcus</italic>, could potentially contribute to the severity of infections observed in this cohort, possibly as co-infections. These microorganisms warrant further investigation into their pathogenic roles and mechanisms of action, as their presence in combination with disease-causing organisms may have a synergistic effect on disease severity. Understanding the interplay between these microorganisms and pathogenic agents could provide valuable insights into the complex nature of severe pediatric infections and guide the development of targeted therapeutic strategies.</p></sec>