腸内細菌由来の超硫黄分子が宿主および細菌の抗酸化能に及ぼす影響

抄録

Introduction: Reactive sulfur species (RSS), such as cysteine persulfide (CysSSH) and glutathione persulfide (GSSH), exhibit high antioxidative property, playing a crucial role in suppressing oxidative stress. The gastrointestinal tract serves as a major site for sulfur metabolism, with gut bacteria contributing to this process. However, it is unclear if commensal gut bacteria produce RSS. We hypothesized that RSS produced by gut bacteria influence the host's antioxidant capacity by contributing to the systemic RSS pool and also serve to protect the gut microbiota from oxidative stress.

Results: The systemic levels of RSS were lower in germ-free mice compared to SPF mice. Gut bacteria enzymatically produced CysSSH from cystine. The plasma RSS level was increased in mice given cystine, which was strongly suppressed by gut microbiota depletion. Single bacterial cultures showed high CysSSH production capacity in Lachnospiraceae and Ruminococcaceae families. Administration of cystine protected mice from concanavalin-A-induced oxidative liver injury in a gut-microbiota-dependent manner. Furthermore, RSS-donor increased RSS levels in the bacteria with low CysSSH production.

Discussion and Conclusion: We identified gut microbes that produce CysSSH from cystine, thereby influencing the systemic RSS level in the host. Our study proposes new mechanisms by which gut-microbiota-derived metabolites contribute to enhancing host antioxidant capacity. Additionally, RSS may enhance antioxidative capacity in bacteria, suggesting a novel gut bacterial interaction facilitated by RSS.