Integrated analysis of fecal microbiome and serum metabolome reveals the profiling of gut microbiota-related metabolites in rats and mice subjected to prolonged exposure to a high-humidity environment

Background: High humidity, as a key climate risk factor, has become one of the significant threats to public health. However, less is known about the mechanism by which the high-humidity environment affects the health of the population. The present study was designed to reveal the profile of gut microbiota-related metabolites in rats and mice subjected to prolonged exposure to a high-humidity environment. Methods: Sprague-Dawley rats and C57BL/6 mice were housed under standard conditions (relative humidity of 60% ± 5%) or prolonged exposure to a high-humidity environment (relative humidity of 90% ± 5%) for 7, 14, and 28 days, respectively. Integrated analysis of fecal microbial diversity and serum metabolome was performed using 16S rRNA sequencing and non-targeted metabolomics with LC-MS/MS. Results: High-humidity exposure led to significant changes in the composition of the gut microbiota and serum metabolic profiles in both rat and mouse models. Our results revealed that disorders in glycerophospholipid metabolism, ABC transporters, and phenylalanine metabolism are key metabolic characteristics of hyperhumidity exposure. In addition, multi-omics correlation analysis identified the key gut microbiota-related metabolites, including phosphocholine, choline, LPC(16:0), taurine, L-valine, L-proline, 2-hydroxycinnamic acid, phenylacetaldehyde, P-salicylic acid, and PC(16:0/20:4(5Z,8Z,11Z,14Z)), which contributed to the pathogenic effect of high humidity. Conclusions: The present study revealed that high-humidity exposure disrupts the host's metabolic homeostasis by altering the gut microbiota-related metabolites in rat and mouse models, showing commonalities and specificities. Our findings may provide new ideas and insights for further study on the pathogenic mechanism of hyperhumidity and intervention strategies targeting the microbiota.