AUTHOR=Yuan Lu , Zhang Rong , Li Xinlou , Gao Caiyun , Hu Xiangnan , Hussain Safdar , Zhang Linlin , Wang Moye , Ma Xiaoyu , Pan Qiuxia , Lou Xiaotong , Si Shaoyan 

TITLE=Long-term simulated microgravity alters gut microbiota and metabolome in mice

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1100747

DOI=10.3389/fmicb.2023.1100747

ISSN=1664-302X

ABSTRACT=<p>Spaceflight and microgravity has a significant impact on the immune, central nervous, bone, and muscle support and cardiovascular systems. However, limited studies are available on the adverse effects of long-term microgravity on the intestinal microbiota, metabolism, and its relationships. In this study, a ground-based simulated microgravity (SMG) mouse model was established to evaluate the impact of long-term microgravity on gut microbiota and metabolome. After 8 weeks of SMG, alterations of the intestinal microbiota and metabolites were detected using 16S rRNA sequencing and untargeted metabolomics. Compared to the control, no significant differences in α-diversity were observed at weeks 2, 4 and 8. Nevertheless, there were clear differences in community structures at different time points. The phylum <italic>Verrucomicrobia</italic> significantly declined from 2 to 8 weeks of SMG, yet the relative abundance of <italic>Actinobacteria</italic> and <italic>Deferribacteres</italic> expanded remarkably at weeks 8. SMG decreased the genus of <italic>Allobaculum</italic> and increased <italic>Bacteroides</italic> significantly throughout the period of 8 weeks. Besides, Genus <italic>Akkermansia</italic>, <italic>Gracilibacter</italic>, <italic>Prevotella</italic>, <italic>Odoribacter</italic>, <italic>Rothia</italic>, <italic>Sporosarcina</italic>, <italic>Gracilibacter</italic>, <italic>Clostridium,</italic> and <italic>Mucispirillum</italic> were identified as biomarkers for SMG group. <italic>Desulfovibrio_c21_c20, Akkermansia_muciniphila</italic>, and <italic>Ruminococcus_gnavus</italic> dropped at week 2, which tend to recover at week 4, except for <italic>Akkermansia_muciniphila</italic>. <italic>Bacteroides_uniformis</italic> and <italic>Faecalibacterium_prausnitzii</italic> declined significantly, while <italic>Ruminococcus_flavefaciens</italic> and <italic>Mucispirillum_schaedleri</italic> elevated at week 8. Furthermore, intestinal metabolome analysis showed that 129 were upregulated and 146 metabolites were downregulated in SMG. Long-term SMG most affected steroid hormone biosynthesis, tryptophan, cysteine, methionine, arginine, proline metabolism, and histidine metabolism. Correlated analysis suggested that the potential beneficial taxa <italic>Allobaculum, Akkermansia</italic>, and <italic>Faecalibacterium</italic> were negatively associated with tryptophan, histidine, arginine, and proline metabolism, but positively with steroid hormone biosynthesis. Yet <italic>Bacteroides, Lachnospiraceae_Clostridium, Rothia, Bilophila,</italic> and <italic>Coprococcus</italic> were positively correlated with arginine, proline, tryptophan, and histidine metabolism, while negatively associated with steroid hormone biosynthesis. These results suggest that Long-term SMG altered the community of intestinal microbiota, and then further disturbed intestinal metabolites and metabolic pathways, which have great potential to help understand and provide clues for revealing the mechanisms of long-term SMG involved diseases.</p>