Impact of hyperoxia on the gut during critical illnesses.

Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.

Corrigendum: Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia.

[This corrects the article DOI: 10.3389/fmicb.2023.1197970.].

Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia.

Background: 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. Methods: C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO2) of 21% and a hyperoxia (OXY) group exposed to FiO2 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. Results: At the phylum level, hyperoxia increased the ratio of Firmicutes/Bacteroidetes (p = 0.049). At the species level, hyperoxia reduced the abundance of Muribaculaceae bacterium Isolate-037 (p = 0.007), Isolate-114 (p = 0.010), and Isolate-043 (p = 0.011) etc. Linear discriminant analysis effect size (LEfSe) revealed that Muribaculaceae and Muribaculaceae bacterium Isolate-037, both belonging to Bacteroidetes, were the marker microbes of the CON group, while Firmicutes 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 (p = 1.10 × 10-11). Hyperoxia blunted fecal linoleic acid metabolism (p = 0.008) and alpha-linolenic acid metabolism (p = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate (p = 1.58 × 10-10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, p = 0.007) and glucagon signaling pathways (p = 0.007). Conclusion: Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant Muribaculaceae 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.