Theranostics
·
2025
·Vol. 15
·期 5
·1741
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IF 13.3
Congcong Yu,Rongtai Sun,Wentao Yang,Tianyuan Gu,Xiaozhang Ying,Lin Ye,Yang Zheng,Shunwu Fan,Xiangjun Zeng,Shasha Yao
Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.
研究领域:
骨骼生物学
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微生物学
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代谢组学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 7
·597-605
·
IF 4.4
Ting Wu,Lu Li,Wenhong Zhou,Guofang Bi,Xiaowen Jiang,Manlan Guo,Xiao Yang,Jianhong Fang,Jianxin Pang,Shicheng Fan,Huichang Bi
Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly.
研究领域:
药理学
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微生物学
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肝脏病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Yajie Cai,Xiaojiaoyang Li,Qi Han,Jinzhao Bai,Qi Zheng,Rong Sun,Runping Liu
Ethnopharmacological relevance Ulcerative colitis (UC) is widely believed to be a leading risk factor of colorectal cancer . Gut microbiota is a known vital player in the progression of UC. Si–Ni-San (SNS) has been considered to effectively treat colitis in clinical practice during thousands of years, yet whether SNS ameliorated acute colitis mouse model by modulating intestinal flora has not been distinctly elucidated. Aim of the study Our study aimed to elucidate the effect of SNS against acute murine colitis and focused on the underlying mechanisms of SNS targeting gut microbiota . Materials and methods 16S RNA sequencing, molecular biological analysis, and fecal microbiota transplants (FMT) were conducted to reveal the mechanisms of SNS in regulating gut microbiota. Results In our study, SNS dramatically inhibited DSS-induced acute inflammatory responses by improving gut microbiota dysbiosis , as evidenced by decreased abundance proinflammatory species, upregulated abundance of anti-inflammatory species and potentially altered microbiota metabolite metabolism. Additionally, intestinal flora knockout and FMT experiments confirmed that the therapeutic effect of SNS on colitis was dependent on gut microbiota, and specifically on favoring the growth of potential probiotics , Akkermansia genus. Furthermore, we found that SNS alone and SNS combined with Akkermansia muciniphila ( A. muciniphila ) increased Mucin 2 (MUC2) production, thus enhancing the competitive edge of A. muciniphila among pathogenic gut microbiota. Conclusion Our study shed lights on the underlying mechanism of SNS in attenuating acute murine colitis from the perspective of intestinal flora and provides novel insights into the discovery of adjacent therapeutic strategy against colitis based on SNS and probiotics. Classification Gastro-intestinal system
研究领域:
消化系统
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药理学
·
微生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Lin Guo,Qijie Guan,Wenhui Duan,Yilin Ren,Xiao-Juan Zhang,Hong-Yu Xu,Jin-Song Shi,Fang-Zhou Wang,Ran Lu,Hui-Ling Zhang,Zheng-Hong Xu,Huazhong Li,Yan Geng
Diet is a major driver of the structure and function of the gut microbiota, which influences the host physiology. Alcohol abuse can induce liver disease and gut microbiota dysbiosis. Here, we aim to elucidate whether the well-known traditional health food Goji berry targets gut microbiota to prevent liver injury induced by acute alcohol intake. The results showed that Goji supplementation for 14 days alleviated acute liver injury as indicated by lowering serum aspartate aminotransferase, alanine aminotransferase, pro-inflammatory cytokines, as well as lipopolysaccharide content in the liver tissue. Goji maintained the integrity of the epithelial barrier and increased the levels of butyric acid in cecum contents. Furthermore, we established the causal relationship between gut microbiota and liver protection effects of Goji with the help of antibiotics treatment and fecal microbiota transplantation (FMT) experiments. Both Goji and FMT-Goji increased glutathione (GSH) in the liver and selectively enriched the butyric acid-producing gut bacterium Akkermansia and Ruminococcaceae by using 16S rRNA gene sequencing. Metabolomics analysis of cecum samples revealed that Goji and its trained microbiota could regulate retinoyl β-glucuronide, vanillic acid, and increase the level of glutamate and pyroglutamic acid, which are involved in GSH metabolism. Our study highlights the communication among Goji, gut microbiota, and liver homeostasis.
研究领域:
营养学
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微生物学
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肝病学
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代谢组学
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传统中药
✓ 已验证
DOI
PubMed
高影响因子
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