Li Lu, Zhao Xiaojie, He Johnny J
Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Center for Cancer Cell Biology, Immunology and Infection, Rosalind Franklin University, North Chicago, IL 60064, USA.
Microorganisms. 2023 Mar 21;11(3):799. doi: 10.3390/microorganisms11030799.
The balance of microbial communities in the gut is extremely important for normal physiological function. Disruption of the balance is often associated with various disorders and diseases. Both HIV infection and cocaine use are known to change the gut microbiota and the epithelial barrier integrity, which contribute to inflammation and immune activation. Our recent study shows that Tat expression and cocaine exposure result in changes of genome-wide DNA methylation and gene expression and lead to worsen the learning and memory impairments. In the current study, we extended the study to determine effects of Tat and cocaine on the gut microbiota composition. We found that both Tat expression and cocaine exposure increased Alteromonadaceae in 6-month-old female/male mice. In addition, we found that Tat, cocaine, or both increased Alteromonadaceae, Bacteroidaceae, Cyanobiaceae, Erysipelotrichaceae, and Muribaculaceae but decreased Clostridiales_vadinBB60_group, Desulfovibrionaceae, Helicobacteraceae, Lachnospiraceae, and Ruminococcaceae in 12-month-old female mice. Lastly, we analyzed changes of metabolic pathways and found that Tat decreased energy metabolism and nucleotide metabolism, and increased lipid metabolism and metabolism of other amino acids while cocaine increased lipid metabolism in 12-month-old female mice. These results demonstrated that Tat expression and cocaine exposure resulted in significant changes of the gut microbiota in an age- and sex-dependent manner and provide additional evidence to support the bidirectional gut-brain axis hypothesis.
肠道中微生物群落的平衡对于正常生理功能极为重要。平衡的破坏通常与各种紊乱和疾病相关。已知HIV感染和可卡因使用都会改变肠道微生物群和上皮屏障完整性，这会导致炎症和免疫激活。我们最近的研究表明，Tat表达和可卡因暴露会导致全基因组DNA甲基化和基因表达的变化，并导致学习和记忆障碍恶化。在当前研究中，我们扩展了研究以确定Tat和可卡因对肠道微生物群组成的影响。我们发现，在6个月大的雌性/雄性小鼠中，Tat表达和可卡因暴露均增加了交替单胞菌科。此外，我们发现，在12个月大的雌性小鼠中，Tat、可卡因或两者均增加了交替单胞菌科、拟杆菌科、蓝细菌科、丹毒丝菌科和毛螺菌科，但减少了梭菌目_vadinBB60_组、脱硫弧菌科、螺杆菌科、毛螺菌科和瘤胃球菌科。最后，我们分析了代谢途径的变化，发现Tat降低了能量代谢和核苷酸代谢，并增加了脂质代谢和其他氨基酸的代谢，而可卡因在12个月大的雌性小鼠中增加了脂质代谢。这些结果表明，Tat表达和可卡因暴露以年龄和性别依赖的方式导致肠道微生物群发生显著变化，并为支持肠道-脑轴双向假说提供了额外证据。
