Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia

• Published in: Frontiers in microbiology 2023-09, Vol.14, p.1197970-1197970
• Main Authors: Cai, Yulan, Luo, Yanhong, Dai, Ninan, Yang, Yan, He, Ying, Chen, Huajun, Zhao, Manlu, Fu, Xiaoyun, Chen, Tao, Xing, Zhouxiong
• Format: Article
• Language: English
• Subjects: gut dysbiosis; gut metabolome; gut microbiome; hyperoxia; metagenomic sequencing; Microbiology; serum metabolome
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2023.1197970

Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study. C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO ) of 21% and a hyperoxia (OXY) group exposed to FiO of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out. At the phylum level, hyperoxia increased the ratio of ( = 0.049). At the species level, hyperoxia reduced the abundance of ( = 0.007), ( = 0.010), and ( = 0.011) . Linear discriminant analysis effect size (LEfSe) revealed that and , both belonging to , were the marker microbes of the CON group, while was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis ( = 1.10 × 10 ). Hyperoxia blunted fecal linoleic acid metabolism ( = 0.008) and alpha-linolenic acid metabolism ( = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate ( = 1.58 × 10 ) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, = 0.007) and glucagon signaling pathways ( = 0.007). Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.