Shu Wang,1,* Chengzhong Liu,2,* Ruipei Ding,2 Shumei Wang,2 Yousheng Ye,1 Maozhang He2 

1Department of Geriatrics, The First People’s Hospital of Hefei, Hefei, 230061, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Maozhang He; Yousheng Ye, Email jnzd_hemaozhang@hotmail.com; ye.ys@qq.com

Background: Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases.
Methods: A total of 25 children were included in the study, comprising 15 pneumonia patients and 10 healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids.
Results: The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0).
Discussion: Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.

Keywords: Mycoplasma pneumoniae, gut microbiota, serum metabolomics, short-chain fatty acids, inflammation