Gut microbiome- targeted intervention ameliorates structural and transcriptomic changes in the kidney of hindlimb unloaded mouse model.

The human body is adapted to Earth's gravity, but space microgravity significantly alters kidney function, with the hindlimb unloaded (HU) mouse model serving as a valuable tool for studying these effects. During space travel, changes in gut microbiota can lead to health-related issues. In this study, we explored the protective role of crocodile gut microbiome media on kidney health in a HU mouse model, given the known impact of space travel on gut microbiota and related health issues. Male C57BL/6 mice (four months old) were divided into a ground-based control group (GC), HU mice fed with distilled water (HU), and HU mice fed with crocodile bacterial conditioned media (HU-CP). All groups were maintained in a controlled environment for three weeks. At the end of the experiment, mice were euthanized, kidney tissues were dissected for histopathological examination and transcriptomic analysis. Statistical analysis was performed using one-way ANOVA followed by Tukey's multiple comparison test, with p < 0.05 considered significant. Transcriptomic analysis revealed distinct gene expression profiles across GC, HU, and HU-CP groups, with HU-CP inducing both unique (4325 genes) and differential (975 genes) expression compared to HU group. The treatment partially restored glomerular morphology, reduced inflammation, and reversed gene expression alterations associated with oxidative stress, apoptosis, fibrosis, and inflammation. The crocodile bacterial conditioned media demonstrated potential therapeutic benefits in mitigating renal injury induced by simulated microgravity in HU mice. Further research is needed to elucidate the specific mechanisms involved and explore the potential clinical applications of this approach.