Cetobacterium somerae mitigates pollutant-induced behavioral abnormalities by modulating host tryptophan metabolism

The gut symbiotic microbiota plays a fundamental role in host health, exerting a widespread influence on brain function and behavior. Environmental pollutants—pervasive in modern life—pose serious threats to both ecological integrity and public health. Notably, their effects may extend to the disruption of host behavioral regulation. However, whether pollutant-induced changes in the structure and function of the gut microbiome contribute causally to behavioral disturbances remains unclear. In particular, little is known about whether core symbiotic taxa can mitigate the detrimental effects of pollutants on the host, or through which molecular mechanisms such protection might occur. In this study, we show that gut symbiotic microbes play a critical role in alleviating anxiety-like behavior in zebrafish. To this end, we first established a zebrafish model of anxiety-like behavior using niclosamide exposure. Microbial diversity analyses revealed pronounced differences in gut microbial community structure between zebrafish exhibiting anxiety-like behavior and normal controls. Subsequently, fecal microbiota transplantation experiments identified Cetobacterium as a key biomarker species associated with anxiety-like behavior. Importantly, oral reintroduction of Cetobacterium effectively mitigated anxiety-like behavior in germ-free zebrafish. Moreover, integrated metabolomic and transcriptomic analyses demonstrated that Cetobacterium modulates host tryptophan metabolism, thereby increasing serotonin (5-HT) levels in both the gut and serum. In contrast, pharmacological inhibition of tryptophan hydroxylase (TPH) reduced 5-HT levels and markedly attenuated the anxiolytic effects of Cetobacterium . Collectively, these findings provide mechanistic insights into how gut symbiotic microbiota regulate host anxiety-like behavior and underscore the beneficial role of core gut symbionts in shaping host cognitive and behavioral functions. Video Abstract