Research
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2023
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IF 11
Nian Liu,Lihui Chen,Mingjie Yan,Qian Tao,Jie Wu,Jing Chen,Xiang Chen,Wei Zhang,Cong Peng
Natural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that Eubacterium rectale was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and that a high E. rectale abundance was related to longer survival in melanoma patients. Furthermore, administration of E. rectale remarkably improved the efficacy of anti-PD1 therapy and increased the overall survival of tumor-bearing mice; moreover, application of E. rectale led to a significant accumulation of NK cells in the tumor microenvironment. Interestingly, conditioned medium isolated from an E. rectale culture system dramatically enhanced NK cell function. Gas chromatography–mass spectrometry/ultrahigh performance liquid chromatography–tandem mass spectrometry-based metabolomic analysis showed that l-serine production was significantly decreased in the E. rectale group; moreover, administration of an l-serine synthesis inhibitor dramatically increased NK cell activation, which enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with l-serine or application of an l-serine synthesis inhibitor affected NK cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.
研究领域:
免疫学
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肿瘤学
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微生物学
✓ 已验证
DOI
高影响因子
Frontiers in Microbiology
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2022
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IF 6.064
Zheng Ya,Chen Juanjuan,Wang Xiaoxuan,Han Ling,Yang Yayuan,Wang Qi,Yu Qunli
Gut microbiome and heredity are two important factors affecting the intramuscular fat (IMF) of cattle, excluding age, sex, and nutrition. This study aimed at deciphering these two differences by analyzing the gut microbiome and intramuscular differentially expressed genes (DEGs) in the Angus and Chinese Simmental cattle. Feces and longissimus dorsi were collected from the two groups of animals (n = 20/group) for multiomics analysis. Angus holds a significantly higher diversity than Chinese Simmental, and the relative abundance of Roseburia, Prevotella, Coprococcus, etc., was obviously higher in Angus. Chinese Simmental had higher levels of isobutyrate, isovalerate, and valerate, although similar levels of acetate, propionate, and butyrate were observed for the two groups. The DEGs upregulated in Chinese Simmental were mainly involved in immune and inflammatory responses, while those in Angus were associated with the regulation of muscle system and myofibril. We finally identified 17 species, including Eubacterium rectale, etc., which were positively correlated to muscle and fat metabolism genes (MSTN, MYLPF, TNNT3, and FABP3/4) and illustrate the associations between them. Our study unveils the gut microbial differences and significant DEGs as well as their associations between the two breeds, providing valuable guidance for future mechanism research and development of intervention strategies to improve meat quality.
研究领域:
动物科学
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微生物学
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基因组学
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营养学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Xianghao Lin,Xiaojuan Zou,Baifei Hu,Dongyun Sheng,Tianxiang Zhu,Mingzhu Yin,Hui Xia,Haiming Hu,Hongtao Liu
This study aimed to evaluate the preventive effect of Bi Xie Fen Qing Yin (BXFQY) decoction on hyperuricemic nephropathy (HN). Using an HN mouse model induced by oral gavage of potassium oxonate and adenine, we found that BXFQY significantly reduced plasma uric acid levels and improved renal function. Further study shows that BXFQY suppressed the activation of the NLRP3 inflammasome and decreased the mRNA expressions of pro-inflammatory and fibrosis-associated factors in renal tissues of HN mice. Also, BXFQY prevented the damage to intestinal tissues of HN mice, indicative of suppressed colonic inflammation and increased gut barrier integrity. By 16 S rDNA sequencing, BXFQY significantly improved gut microbiota dysbiosis of HN mice. On the one hand, BXFQY down-regulated the abundance of some harmful bacteria, like Desulfovibrionaceae, Enterobacter , Helicobacter, and Desulfovibrio . On the other hand, BXFQY up-regulated the contents of several beneficial microbes, such as Ruminococcaceae, Clostridium sensu stricto 1 , and Streptococcus . Using gas or liquid chromatography-mass spectrometry (GC/LC-MS) analysis, BXFQY reversed the changes in intestinal bacterial metabolites of HN mice, including indole and BAs. The depletion of intestinal flora from HN or HN plus BXFQY mice confirmed the significance of gut microbiota in BXFQY-initiated treatment of HN. In conclusion, BXFQY can alleviate renal inflammation and fibrosis of HN mice by modulating gut microbiota and intestinal metabolites. This study provides new insight into the underlying mechanism of BXFQY against HN.
研究领域:
药理学
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肾病学
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微生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）