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Gut microbial balance and liver transplantation: alteration, management, and prediction

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《医学前沿（英文）》 2018年第12卷第2期页码 123-129 doi: 10.1007/s11684-017-0563-2

摘要：

Liver transplantation is a conventional treatment for terminal stage liver diseases. However, several complications still hinder the survival rate. Intestinal barrier destruction is widely observed among patients receiving liver transplant and suffering from ischemia–reperfusion or rejection injuries because of the relationship between the intestine and the liver, both in anatomy and function. Importantly, the resulting alteration of gut microbiota aggravates graft dysfunctions during the process. This article reviews the research progress for gut microbial alterations and liver transplantation. Especially, this work also evaluates research on the management of gut microbial alteration and the prediction of possible injuries utilizing microbial alteration during liver transplantation. In addition, we propose possible directions for research on gut microbial alteration during liver transplantation and offer a hypothesis on the utilization of microbial alteration in liver transplantation. The aim is not only to predict perioperative injuries but also to function as a method of treatment or even inhibit the rejection of liver transplantation.

关键词： gut microbial balance liver transplantation ischemia–reperfusion acute rejection

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Integrated analysis of gut microbiome and host immune responses in COVID-19

《医学前沿（英文）》 2022年第16卷第2期页码 263-275 doi: 10.1007/s11684-022-0921-6

摘要： Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3⁺/CD4⁺/CD8⁺ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19 SARS-COV-2 gut microbiome immune response

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Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

Ruiting Han, Junli Ma, Houkai Li

《医学前沿（英文）》 2018年第12卷第6期页码 645-657 doi: 10.1007/s11684-018-0645-9

摘要： Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical “Two-hit” theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a “metabolic organ” that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

关键词： gut microbiota NAFLD obesity insulin resistance bile acids probiotic

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Calorie restriction and its impact on gut microbial composition and global metabolism

Xiaojiao Zheng, Shouli Wang, Wei Jia

《医学前沿（英文）》 2018年第12卷第6期页码 634-644 doi: 10.1007/s11684-018-0670-8

摘要：

Calorie restriction (CR) is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. It has long been recognized as a natural strategy for promoting health, extending longevity, and prevents the development of metabolic and age-related diseases. In the present review, we focus on the general effect of CR on gut microbiota composition and global metabolism. We also propose mechanisms for its beneficial effect. Results showed that probiotic and butyrate-producing microbes increased their relative abundance, whereas proinflammatory strains exhibited suppressed relative abundance following CR. Analyses of the gut microbial and host metabolisms revealed that most host microbial co-metabolites were changed due to CR. Examples of dramatic CR-induced changes in host metabolism included a decrease in the rate of lipid biosynthesis and an increase in the rates of fatty acid catabolism, β-oxidation, glycogenolysis, and gluconeogenesis. The observed phenotypes and the further verification of the direct link between gut microbiota and metabolome may benefit patients that are at risk for developing metabolic disease. Thus, improved gut microbiota composition and metabolome are potential biomarkers for determining the effectiveness of dietary interventions for age-related and metabolic diseases.

关键词： caloric restriction gut microbiota metabolome

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ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis

《医学前沿（英文）》页码 972-992 doi: 10.1007/s11684-023-0990-1

摘要： Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

关键词： inflammatory bowel disease ADT-OH intestinal permeability gut microbiota

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From gut changes to type 2 diabetes remission after gastric bypass surgeries

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《医学前沿（英文）》 2013年第7卷第2期页码 191-200 doi: 10.1007/s11684-013-0258-2

摘要：

Increasing evidence suggests that the gut may influence the host’s metabolism and ultimately change the outcomes of type 2 diabetes mellitus (T2DM). We review the evidence on the relationship between the gut and T2DM remission after gastric bypass surgery, and discuss the potential mechanisms underlying the above relationship: gut anatomical rearrangement, microbial composition changes, altered gut cells, and gut hormone modulation. However, the exact changes and their relative importance in the metabolic improvements after gastric bypass surgery remain to be further clarified. Elucidating the precise metabolic mechanisms of T2DM resolution after bypass surgery will help to reveal the molecular mechanisms of pathogenesis, and facilitate the development of novel diagnoses and preventative interventions for this common disease.

关键词： gastric bypass T2DM gut

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Pien Tze Huang Protects Against Non-Alcoholic Steatohepatitis by Modulating the Gut Microbiota and Metabolites

Xianyi Zeng,Xiang Zhang,Hao Su,Hongyan Gou,Harry Cheuk-Hay Lau,Xiaoxu Hu,Ziheng Huang,Yan Li,Jun Yu,

《工程（英文）》 doi: 10.1016/j.eng.2022.10.010

摘要： Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease without effective treatment. The traditional Chinese medicine formulation Pien Tze Huang (PTH) can suppress inflammatory diseases. Here, we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms. We found that PTH prevented the development of steatohepatitis induced by various dietary models, including a high-fat high-cholesterol (HFHC) diet, choline-deficient high-fat diet (CD-HFD), and methionine- and choline-deficient (MCD) diet, along with significant suppression of liver injury, hepatic triglyceride, and lipid peroxidation. Moreover, ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice. Through the metagenomic sequencing of stool samples, we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus (L. acidophilus), Lactobacillus plantarum, Lactococcus lactis, and Bacillus subtilis. The enriched L. acidophilus prevented MCD diet-induced steatohepatitis. In addition, PTH restored the gut barrier function in mice with steatohepatitis, as evidenced by reduced intestinal permeability, decreased serum lipopolysaccharides (LPS) level, and increased epithelial tight-junction protein E-cadherin expression. Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTH-treated mice. We further confirmed that an intact gut microbiota is necessary for PTH to exhibit anti-steatohepatitis effects. In conclusion, PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites. PTH is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang Non-alcoholic steatohepatitis Gut barrier function Gut microbiota

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Biodegradation of waste refrigerator polyurethane by mealworms

《环境科学与工程前沿（英文）》 2023年第17卷第3期 doi: 10.1007/s11783-023-1638-8

摘要：

● Waste refrigerator polyurethane (WRPU) was ingested and biodegraded by mealworms.

关键词： Waste refrigerator polyurethane Mealworms Biodegradation Carbon balance Gut microorganism

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病理状态下肠道微生态的调节

王玉兰, 王保红, 吴俊芳, 江向洋, 唐惠儒, Ole H. Nielsen

《工程（英文）》 2017年第3卷第1期页码 83-89 doi: 10.1016/J.ENG.2017.01.013

摘要：

人类微生态是寄居在人体中的微生物聚集体，且主要存在于胃肠道(GIT) 中。肠道微生态随着人体发育而演化，并在人类健康和疾病中起着重要作用。近年来，由于微生态会影响宿主代谢、生理学和免疫系统发育，而且微生态紊乱可能导致许多疾病，其越来越受到人们的关注。肠道微生态可能与恶性肿瘤有一定联系，如胃癌和结直肠癌；也可能与其他一些疾病有关，如非酒精性脂肪肝(NAFLD)、被称为工业化世界“生活方式疾病”的肥胖和糖尿病、冠心病以及中枢神经系统紊乱。虽然分子技术革命为我们更准确地研究肠道微生态提供了必要的工具，但是我们需要更精确地阐明其与某些人类疾病病理变化的关系，明确微生态在不同疾病中的作用是新的治疗策略发展的基础。本文概述了肠道微生态对人类健康的重要影响以及调整肠道菌群结构的潜在用途，如菌群移植用于治疗耐药艰难梭菌(C. difficile) 的感染。通过微生态干预调整肠道区域以改善人类健康的概念虽刚刚兴起，但其治疗意义显著。因此，抑制有害菌、促进有益菌可能会保护人类健康，并且这些努力将为探索发展更加合理的治疗方案打下基础。

关键词：肠道菌群疾病菌群调节

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Gut microbiota and its implications in small bowel transplantation

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《医学前沿（英文）》 2018年第12卷第3期页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要：

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词： gut microbiota small bowel transplantation acute rejection chronic rejection mucosal immunity biomarker microbiota-targeted therapy

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肠道菌群与肿瘤发生及肝病

吕桂帅, 程宁涛, 王红阳

《工程（英文）》 2017年第3卷第1期页码 110-114 doi: 10.1016/J.ENG.2017.01.017

摘要：

一个多世纪以前，科学家们就首次发现了肿瘤区域中细菌的存在。但是，微生物在肿瘤发生中的作用近年来才被认识到。近几十年来，与肠道菌群失调相关的疾病代表了全世界最严重的一些公共卫生问题。大量的流行病学研究表明，肠道菌群与某些常见肿瘤密切相关。然而，肠道菌群与肿瘤相关联的具体分子机制仍不明确。研究表明，肠道菌群的改变有助于确定肝癌、酒精相关肝病、非酒精性脂肪肝和肝硬化的发生和发展。鉴于益生菌是一种可通过调节免疫系统促进人类健康的药物，其可能会为肝细胞癌(HCC) 和非酒精性脂肪肝的治疗提供新方向。本文总结了肠道菌群在肿瘤及肝病中的研究进展，综述了肠道菌群与肿瘤和肝病之间的关系。此外，考虑到细菌内稳态的重要性，我们也对益生菌进行了概述，旨在为相关疾病的治疗提供指导。

关键词：肠道菌群稳态失调肿瘤发生肝细胞癌非酒精性脂肪性肝病

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通过调控肠道菌群治疗慢性疾病

洪斌, 蒋建东

《工程（英文）》 2022年第18卷第11期页码 17-20 doi: 10.1016/j.eng.2021.08.015

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Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

《工程（英文）》 doi: 10.1016/j.eng.2023.06.007

摘要： Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1^Δ^IEC) and Paneth cell (PC; Axin1^Δ^PC) to compare with control (Axin1^LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1^Δ^IEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium-induced colitis in vivo. Axin1^Δ^IEC and Axin1^Δ^PC mice became more susceptible to dextran sulfate sodium (DSS)-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1^Loxp mice. However, the intestinal proliferative cells in Axin1^Δ^IEC mice with antibiotic treatment were reduced compared with those in Axin1^Δ^IEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

关键词： Axin1 Bacteria Microbiome inflammation Inflammatory bowel disease Immunity Microbiome Paneth cells Akkermansia muciniphila Wnt

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Analysis of interactions of immune checkpoint inhibitors with antibiotics in cancer therapy

《医学前沿（英文）》 2022年第16卷第3期页码 307-321 doi: 10.1007/s11684-022-0927-0

摘要： The discovery of immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4, has played an important role in the development of cancer immunotherapy. However, immune-related adverse events often occur because of the enhanced immune response enabled by these agents. Antibiotics are widely applied in clinical treatment, and they are inevitably used in combination with immune checkpoint inhibitors. Clinical practice has revealed that antibiotics can weaken the therapeutic response to immune checkpoint inhibitors. Studies have shown that the gut microbiota is essential for the interaction between immune checkpoint inhibitors and antibiotics, although the exact mechanisms remain unclear. This review focuses on the interactions between immune checkpoint inhibitors and antibiotics, with an in-depth discussion about the mechanisms and therapeutic potential of modulating gut microbiota, as well as other new combination strategies.

关键词： tumor immunotherapy immune checkpoint inhibitor antibiotics gut microbiota drug–drug interaction

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肠道菌群是调节神经系统功能紊乱的潜在靶点 Review

武万强, 孔庆敏, 田培郡, 翟齐啸, 王刚, 刘小鸣, 赵建新, 张灏, Yuan Kun Lee, 陈卫

《工程（英文）》 2020年第6卷第4期页码 415-423 doi: 10.1016/j.eng.2019.07.026

摘要：

众所周知，肠道菌群在调节宿主生理功能方面具有重要作用，如调节免疫和代谢平衡。近年来，越来越多证据表明肠道菌群能够通过肠-脑轴调节中枢神经系统功能，这为研究肠道和大脑间的相互作用关系开辟了一条新路径。本文首先介绍了肠道菌群与大脑相互作用的肠–脑轴分子机制，以及肠道菌群失调引发的神经系统功能紊乱；然后介绍了调节肠道菌群失衡是干预神经系统功能紊乱的潜在策略，如益生菌、益生元、合生元以及饮食等干预措施。目前关于肠道菌群–肠–脑轴方面的研究尚处在起步阶段，但继续深入阐明肠道菌群调节神经系统功能的分子机制不仅能揭示神经系统功能紊乱的新型病理机制，而且能够为神经系统功能紊乱提供潜在的诊断标志物和干预策略。

关键词：肠道菌群肠-脑轴神经系统功能紊乱干预策略