Space flight has many adverse effects on the physiological functions of astronauts. Certain similarities have been observed in some physiological processes of rodents and astronauts in space, although there are also differences. These similarities make rodents helpful models for initial investigations into space-induced physiological changes. This study uses a 3D-Clinostat to simulate microgravity and explores the role of microgravity in space flight-induced liver and brain abnormalities by comparing changes in the gut microbiota, serum metabolites, and the function and physiological biochemistry of liver and brain tissues between the simulated microgravity (SMG) group mice and the wild type (WT) group mice. The study, based on hematoxylin-eosin (HE) staining, 16S sequencing technology, and non-targeted metabolomics analysis, shows that the gut tissue morphology of the SMG group mice is abnormal, and the structure of the gut microbiota and the serum metabolite profile are imbalanced. Furthermore, using PICRUST 2 technology, we have predicted the functions of the gut microbiota and serum metabolites, and the results indicate that the liver metabolism and functions (including lipid metabolism, amino acid metabolism, and sugar metabolism, etc.) of the SMG group mice are disrupted, and the brain tissue metabolism and functions (including neurotransmitters and hormone secretion, etc.) are abnormal, suggesting a close relationship between microgravity and liver metabolic dysfunction and brain dysfunction. Additionally, the high similarity in the structure of the gut microbiota and serum metabolite profile between the fecal microbiota transplant (FMT) group mice and the SMG group mice, and the physiological and biochemical differences in liver and brain tissues compared to the WT group mice, suggest that microgravity induces imbalances in the gut microbiota, which in turn triggers abnormalities in liver and brain metabolism and function. Finally, through MetaMapp analysis and Pearson correlation analysis, we found that valeric acid, a metabolite of gut microbiota, is more likely to be the key metabolite that relates to microgravity-induced gut microbiota abnormalities, disorders of amino acid and lipid metabolism, and further induced metabolic or functional disorders in the liver and brain. This study has significant practical application value for deepening the understanding of the adaptability of living organisms in the space environment.

PM_2.5, recognized as a potential pathogenic factor for nervous system diseases, remains an area with many unknowns, particularly regarding its effects on human health. After five-month real-ambient PM_2.5 exposure, we observed no significant pathological damage to the lung, liver, spleen, or kidney tissues. However, PM_2.5 exposure led to neuronal degeneration in the hippocampal CA1 region of Brown Norway (BN) rats. The level of IL-6, IL-13, IL-1β, IL-12, IL-4, GRO/KC, MIP-1α, CM-CSF significantly increased in lung lavage fluid (P < 0.05 for all). Notably, we detected a slight impairment in spatial learning ability, as evidenced by the Barnes maze training outcomes. There were no significant changes in the bacterial community in lung lavage fluid (P = 0.621), but the bacterial community in the gut significantly changed (P < 0.001), with more species identified (P < 0.05). The metabolomic analysis revealed 147 and 149 significantly changed metabolites in the pulmonary system and serum, respectively (P < 0.05). PM_2.5 exposure caused a decrease in Nervonic acid (NA) in both the lung and serum, which likely contributed to spatial learning impairment (P < 0.01). The correlation between lung metabolites, gut bacterial species, and serum metabolites indicated that PM_2.5 exposure likely impaired spatial learning through the lung-gut-brain axis pathway. Lung and serum metabolic disorders and intestinal microbial imbalance occurred in BN rats post-five-month real-ambient PM_2.5 exposure. There were two potential ways that PM_2.5 exposure caused the decline of spatial learning ability in wild-type BN rats: (1) PM_2.5 exposure led to a significant decrease of neuroprotective Nervonic acid in lung and serum metabolites. (2) PM_2.5 exposure likely led to reduced spatial learning ability through the lung-gut-brain axis.

Background: The effects of variation in airborne bacterial community composition on the respiratory microbiota and host metabolism remain poorly understood. Method: Five artificial bacterial communities were constructed using the same 16 airborne bacterial strains at different relative abundances. Male BALB/c mice were randomly assigned to six groups (n = 6) and intranasally instilled with saline or the corresponding artificial bacterial community (Abc-C1–Abc-C5) five times per week for four weeks. Enzyme-linked immunosorbent assay (ELISA), 16S rRNA gene sequencing, and untargeted metabolomics were used to assess inflammatory mediator levels, bacterial community composition, and local and systemic metabolic profiles, respectively. Results: Compared with the saline control group, plasma IL-6 levels were significantly decreased in the Abc-C3 and Abc-C5 groups. In BALF, IL-1β levels did not differ significantly between any exposure group and the saline group; however, they were higher in the Abc-C3 and Abc-C5 groups than in the Abc-C1 group. Microbial α-diversity did not differ significantly among groups, whereas overall community composition differed significantly (p = 0.001). Seven differentially abundant genera were identified: Acinetobacter, Acidiphilium, Bacillus, Rhodopseudomonas, Bradyrhizobium, Burkholderia–Caballeronia–Paraburkholderia, and Ralstonia. Metabolomic analysis revealed alterations in amino acid-related metabolites in BALF, whereas amino acid derivatives and acylcarnitines in plasma exhibited distinct patterns of change. Eight enriched KEGG pathways overlapped between BALF and plasma. Spearman correlation analysis was used to construct a correlation network linking pulmonary bacterial genera, BALF metabolites, and plasma metabolites (|r| > 0.4 and q < 0.05). Conclusions: This study demonstrates that, even when bacterial species and total exposure concentration were held constant, exposure to airborne bacterial communities with different relative compositions was associated with differences in the pulmonary microbiota, local and systemic metabolism, and certain inflammatory responses in mice. These findings suggest that the relative composition of bacterial communities may be an important determinant of host responses to microbial exposure and provide a basis for further investigation into the potential links between the respiratory microbiota and systemic metabolism.