Cell Host & Microbe
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2022
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IF 31.316
Haiyang Lu,Xiaoqiang Xu,Di Fu,Yubei Gu,Rong Fan,Hongmei Yi,Xiangyi He,Chaofu Wang,Binshen Ouyang,Ping Zhao,Li Wang,Pengpeng Xu,Shu Cheng,Zhifeng Wang,Duowu Zou,Lizhong Han,Weili Zhao
Summary Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale . Transfer of E. rectale -deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.
研究领域:
肿瘤学
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免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2026
·Vol. 15
·期 5
·e70293
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IF 21.7
Jiaqi Wang,Gulisudumu Maitiabula,Sirui Liu,Ruowen Li,Shijie Wang,Pinwen Zhou,Yufei Xia,Longchang Huang,Xin Chen,Xuejin Gao,Li Zhang,Xinying Wang
Cancer cachexia (CC) is a complex pathological condition associated with cancer progression and poor prognosis, particularly in gastrointestinal cancers, and is closely linked to the gut microbiota. Lipolysis in CC may play a key role in driving cachexia progression. However, the role of the gut microbiota in CC-induced lipolysis and the underlying mechanisms remains unclear. In this study, we found that significant gut microbiota dysbiosis in pancreatic cancer cachexia, characterized by diminished abundance of Eubacterium rectale ( E.rectale ), was negatively associated with lipolysis severity. Furthermore, we demonstrated for the first time that E. rectale derived extracellular vesicles (EVs) can ameliorate lipolysis across multiple CC models. Mechanistically, these effects are mediated by modulating pro-inflammatory macrophages through inhibition of NF-kB signalling, reducing macrophage polarization and inflammatory cytokine secretion. Our findings indicated E. rectale EVs could offer potential therapeutic benefits for CC and emphasize the importance of host-microbiota interactions. Trial Registration : This study was registered at ClinicalTrials.gov (NCT06378853).
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DOI
PubMed
高影响因子
Research
·
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
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DOI
高影响因子
Food Chemistry-X
·
2021
·
IF 5.182
Tao Xu,Weisu Huang,Jiajia Liang,Yongheng Zhong,Qi Chen,Fan Jie,Baiyi Lu
The different health effects between starch and whole flour from tubers are rarely studied. Here, we investigated the effects of cassava flour (CF), cassava starch (CS), potato flour (PF), and potato starch (PS) on gut health and gut microbiota of normal rats. Feed analysis showed that CF and PF diet provided significantly more slowly digestible and resistant starch, less rapidly digestible starch. Compared with rats fed with PS and CS diets, rats fed with PF and CF diets gained less body weight and have tighter intestinal barrier. Butyric acid contents were increased by tuber flours. CF and PF selectively promoted the relative abundance of Akkermansia and Eubacterium ruminantium in cecal and colonic content. In conclusion, tuber flour has intestinal protection, body weight control, and gut microbiota improving ability compared with starch. The different composition of starch might be the basis for these effects.
研究领域:
营养学
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胃肠病学
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微生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Yuanyuan Zhao,Jinfeng Bi,Jianyong Yi,Xinye Wu,Youchuan Ma,Ruiping Li
The intestinal fermentability of pectic polysaccharides is largely determined by its molecular size. In this study, fermentation properties of enzymatic-modified apple pectin (AP) and homogalacturonans (HG) with high, medium and low molecular weight (Mw) were evaluated by in vitro fermentation model , and their structural changes were also investigated. Results showed that Mw, monosaccharide contents and molecular linearity of the AP hydrolysates were reduced after microbial degradation . On the other hand, culture media supplemented with low-Mw AP (60,300 g/mol) and low-Mw HG (861 g/mol) exhibited lower pH (5.1 and 5.7, respectively) and produced higher total short-chain fatty acid contents (SCFA, 230.40 mmol/L and 187.19 mmol/L, respectively). However, reduced trends in abundance of the pectinolytic microorganisms Faecalibacterium and Eubacterium were showed as Mw of the HG decreased, whereas growth of the SCFA-producer genera Bifidobaacterium , Megasphaera and Allisonella were improved. This work confirmed that low-Mw pectin and homogalacturonan generated more beneficial metabolites, developing structure-microbiota-gut health relationship.
研究领域:
胃肠病学
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微生物学
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营养学
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食品科学
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产品关联
DOI
PubMed
高影响因子
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