JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Mingxia Ma,Yanxin Wang,Siqing Fan,Yumeng Huang,Xiurong Su,Chenyang Lu
Urolithin A (UroA) is a microbial metabolite derived from ellagitannins and ellagic acid with good bioavailability. In this study, we explored the anticolitis activity of UroA and clarified the mechanism by 16S rDNA sequencing and metabonomics. UroA alleviated dextran sulfate sodium (DSS)-induced colitis in mice, characterized by a decreased disease activity index, increased colon length, and improved colonic histopathological lesions, along with inhibited phosphorylation of the mitogen-activated protein kinase signaling pathway. In addition, UroA improved gut microbiota dysbiosis and modulated the microbiota metabolome. Furthermore, targeted metabolomics focused on tryptophan catabolites showed that UroA significantly increased the production of indole-3-aldehyde (IAld) and subsequently led to increased colonic expression of aryl hydrocarbon receptor (AhR) and promoted the serum content of IL-22 in mice with colitis. Collectively, our data identified a novel anticolitis mechanism of UroA by improving gut microbiota dysbiosis, modulating microbial tryptophan metabolism, promoting IAld production, and triggering AhR/IL-22 axis activation. However, a limitation noted in this study is that these beneficial effects of UroA were found at 50 μM in vitro and 20 mg/kg in vivo, which were nonphysiological concentrations.
研究领域:
药理学
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免疫学
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微生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Juanhui Lin,Yuansong Wei,Xiaxian Gu,Miaoru Liu,Mengru Wang,Renxiang Zhou,Duowu Zou,Lichen Yin,Chunhua Zhou,Duanmin Hu
Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas accompanied with intestinal injury, and effective therapeutic modalities are still highly lacking. Herein, a facile and effective nanotherapeutics (pHA@IBNCs) is developed to alleviate pancreatic inflammation and restore intestinal barrier for SAP treatment. Epigallocatechin gallate (EGCG, an anti-oxidant), interleukin-22 (IL-22, an anti-inflammatory and epithelial barrier-protecting cytokine), and bovine serum albumin (a framework protein), are assembled via non-covalent interactions to form nanocomplexes (IBNCs). Then, phenylboronic acid-modified hyaluronic acid (pHA) is synthesized and coated onto IBNCs via formation of the reversible boronate ester bonds to obtain pHA@IBNCs. Upon intravenous injection, pHA@IBNCs could efficiently accumulate at the lesion sites of sodium taurocholate (STC)-induced SAP mice, based on their prolonged blood circulation time and pHA-mediated targeting of activated intestinal epithelial cells and macrophages. Inside the inflammatory microenvironment, over-produced reactive oxygen species (ROS) trigger the shedding of the pHA layer and release of the drug payloads. Thereby, EGCG cooperates with IL-22 to attenuate pancreatitis and restore the intestinal barrier by scavenging ROS, suppressing pro-inflammatory cytokines secretion, and promoting the repair of intestinal epithelia. Such a nano-therapeutic approach targeting multiple pathological events may serve as a promising paradigm for the effective management of SAP.
研究领域:
纳米医学
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炎症学
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胃肠病学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Ruopeng Yin,Tao Wang,Jingzu Sun,Huanqin Dai,Yuting Zhang,Ningning Liu,Hongwei Liu
Prolonged alcohol consumption disrupts the gut microbiota and the immune system, contributing to the pathogenesis of alcohol-associated liver disease (ALD). Probiotic-postbiotic intervention strategies can effectively relieve ALD by maintaining gut homeostasis. Herein, the efficacy of heat-killed Lactobacillus johnsonii (HKLJ) in mitigating alcoholic liver damage is demonstrated in mouse models of ALD. The gut-liver axis is identified as a pivotal pathway for the protective effects of L. johnsonii against ALD. Specifically, HKLJ is found to upregulate the expression of intestinal lysozymes, thereby enhancing the production of immunoregulatory substances from gut bacteria, which subsequently activated the Nucleotide-binding oligomerization domain 2 (NOD2)-interleukin (IL-23)-IL-22 innate immune axis. The elevated IL-22 upregulated the antimicrobial peptide synthesis to maintain intestinal homeostasis and moreover activated the Signal transducer and activator of Transcription3 (STAT3) pathway in the liver to facilitate the repair of hepatic injuries. The heat-killed L. johnsonii provoked immunity helps correct the gut microbiota dysbiosis, specifically by reversing the reduction of butyrate-producing bacteria (such as Faecalibaculum rodentium ) and the expansion of opportunistic pathogens (such as Helicobacter sp. and Pichia kudriavzevii ) induced by ethanol. The findings provide novel insights into the gut microbiota-liver axis that may be leveraged to enhance the treatment of ALD.
研究领域:
微生物学
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免疫学
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肝病学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 16
·7343-7357
·
IF 5.396
Songtao Fan,Zhihong Zhang,Yadong Zhong,Chang Li,Xiaojun Huang,Fang Geng,Shaoping Nie
Fructans such as fructo-oligosaccharides (FOS) and inulin have been reported to directly regulate ileal inflammatory responses in lipopolysaccharide (LPS)-induced endotoxemic mice, without alterations in the colonic microbiota. Firstly, we replicated this model and found that a single gavage of 10 mg g−1 of fructans directly promoted caecal acetate and propionate production. Thus, the previous understanding of microbiota-independent effects of prebiotic fructans in endotoxemic mice has been challenged. In parallel, we performed a daily gavage of 160 mg kg−1 of inulin, xylan, or Dendrobium officinale polysaccharides (DOP) for two weeks prior to LPS injection. The long-term intake of prebiotic fibres reduced the bacterial load in the spleen and mesenteric lymph nodes (MLNs), and in comparison, a single gavage of fructans increased that. However, the long-term intake was unable to improve the short-chain fatty acid (SCFA) synthesis and epithelial barrier function that were impaired by LPS. Notably, the three fibre types consistently reduced the expression of mucin 2 (MUC2) and variously modulated critical mediators (IL-18, IL-22, and HIF-1α) to regulate the host–commensal microbiota interactions in the ileum. In addition, the three fibre types consistently inhibited the inflammatory T helper (Th) cell response in the ileum, while they diversely modulated the peripheral and systemic Th cell responses. Overall, the prebiotic fibres displayed microbiota-related changes in endotoxemic mice, and the potential associations with the in vivo anti-inflammatory effects of prebiotic fibres need further investigation.
研究领域:
胃肠病学
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免疫学
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微生物学
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营养学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Xiudan Wang,Rui Tian,Chenghong Liang,Yifan Jia,Lingyun Zhao,Qinyuan Xie,Fenglian Huang,Huijuan Yuan
Insulin resistance and pancreatic β -cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H 2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β -cell and enhanced pancreatic β -cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.
研究领域:
纳米技术
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糖尿病研究
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胃肠病学
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药理学
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分子生物学
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免疫学
✓ 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）