Cadmium toxicity to the human gut microbiome varies depending on composition

Cadmium (Cd) is a toxic heavy metal with detrimental impacts on the gut microbiota. We investigated the compositional and functional effects of acute Cd exposure on human fecal microbiotas using 24-hour in vitro cultures from 21 healthy adult donors. Regression analysis of butyrate production in the absence (Cd-) versus presence (Cd+) of Cd identified three categories of microbial responses: sensitive, intermediate, and resilient. Under Cd stress, sensitive microbiomes exhibited significant decreases in butyrate [-3.22±0.96 log₂(Cd+/Cd-), p=0.001] coupled with elevated acetate [1.53±1.83 log₂(Cd+/Cd-), p=0.003] and lactate [1.86±0.95 log₂(Cd+/Cd-), p=0.001] production. In contrast, resilient microbiomes did not show significant changes in butyrate [0.22±0.43 log₂(Cd+/Cd-), p=0.59] or acetate [-0.18±0.35 log₂(Cd+/Cd-), p=0.26] and exhibited attenuated increases in lactate compared with sensitive microbiomes [0.45±0.43 versus 1.86±0.95 log₂(Cd+/Cd-), p=0.002]. Sensitive microbiomes had a larger shift in global microbiota composition under Cd stress than resilient microbiomes (weighted UniFrac distance: 0.098±0.026 versus 0.073±0.035, p=0.04). Several genera were significantly different between sensitive and resilient communities after exposure to Cd, but the most striking was Anaerostipes (7.15 centered-log-ratio difference, Cd+/Cd-, q<0.001). Network analysis revealed a significantly greater disruption of microbial interactions in sensitive communities compared with resilient (χ² = 9.21, p = 0.002). Multivariable Association with Linear Models revealed that, in resilient communities, butyrate production was primarily associated with Faecalibacterium in the absence of Cd (q<0.001) and Anaerostipes in the presence of Cd (q=0.005). These findings highlight distinct gut microbial responses to acute Cd exposure and provide a foundation to investigate microbiota features underlying Cd sensitivity or resilience.