Hyperoxia as a driver of gut dysbiosis

Hang Wu¹Wenxia Zeng¹Ninan Dai¹Juan Gu²Ying He¹Han Qin³Long Lin⁴Xiaoyun Fu^1*Bao Fu^1*Zhouxiong Xing^1*

• ¹Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China
• ²Department of Pharmacy, Affiliated Hospital of Zunyi Medical University, Zunyi, China
• ³Department of Respiratory and Critical Care Medicine, KweiChow Moutai Hospital, Zunyi, China
• ⁴Department of Nephrology, KweiChow Moutai Hospital, Zunyi, China

The mammalian colon lumen exists in a highly anaerobic environment (oxygen partial pressure (PO2) < 1 mmHg), which promotes the growth of beneficial obligate anaerobes (OA) while limiting the expansion of pathogenic facultative anaerobes (FA). Gut dysbiosis is associated with a wide range of human diseases, and is often characterized by an overgrowth of FA, particularly those in the Enterobacteriaceae family. Oxygen (O2) plays a crucial role in bacterial physiology and ecology, and increased O2 availability is a key driver of gut dysbiosis. O2 therapy is commonly used for hypoxic patients, either through inhalation or extracorporeal membrane oxygenation (ECMO), both of which can expose the gut to excess O2, known as hyperoxia. Hyperoxia leads to the overproduction of reactive O2 species, resulting in organ injury and worsening clinical outcomes. Viewing gut dysbiosis from an ecological perspective highlights the disruption of host mechanisms that regulate the gut microbiota, This is a provisional file, not the final typeset article particularly in the context of antibiotic use and a western (low fiber) diet, where physiological hypoxia in the colonic epithelium is compromised. This review extends that perspective to O2 therapy in acute care, discussing the rationale and experimental evidence linking hyperoxia to gut dysbiosis, with a focus on venoarterial (VA)-ECMO support as a potential contributor. Understanding these mechanisms could help clinicians optimize O2 management during therapy.