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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; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC 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. Axin1ΔIEC and Axin1ΔPC 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 Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC 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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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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Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 314-329 doi: 10.1007/s11684-018-0625-0

摘要： The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNF and IL-1 ) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

关键词： cytokines     inflammation     adipogenesis     type 2 diabetes mellitus     metabolic disorder    

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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

《医学前沿（英文）》 doi: 10.1007/s11684-023-1029-3

摘要： Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

关键词： tumor prognosis molecular     Microbiome subsets determine     center analysis microbiome     transcriptome data    

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Appendiceal inflammation affects the length of stay following appendicectomy amongst children: a myth

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 264-269 doi: 10.1007/s11684-013-0259-1

摘要：

The effect of the severity of appendiceal inflammation on post-operative stay in children following appendicectomy has shown conflicting results. This study was conducted to determine the association between the severity of appendiceal inflammation and post-operative stay amongst children undergoing open appendicectomy. A retrospective cohort study was conducted at a District General Hospital for two years. A total of 204 patients were included in the study with an age range between 3 and 16 years. Females were 54.9% while the rest were male. Mean age was 12.5±3 years. The association of the severity of appendiceal inflammation and post-operative stay was assessed by multivariable Cox Proportional hazards model. Mean post-operative stay was 2.32 days (95% CI 2.14–2.51). Macroscopically perforated appendix, histological inflammation and post-operative complications were significantly associated with post-operative stay on univariable analysis (P<0.05). Whereas, the multivariable analysis showed that the post-operative stay was significantly prolonged only in case of either perforated appendix or post-operative complications while it remained unaffected by the histological inflammation.

关键词： appendiceal inflammation     post-operative stay     paediatrics    

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Understanding building-occupant-microbiome interactions toward healthy built environments: A review

Shuai Li, Zhiyao Yang, Da Hu, Liu Cao, Qiang He

《环境科学与工程前沿（英文）》 2021年 第15卷 第4期 doi: 10.1007/s11783-020-1357-3

摘要： Abstract • The built environment, occupants, and microbiomes constitute an integrated ecosystem. • This review summarizes research progress which has focused primarily on microbiomes. • Critical research needs include studying impacts of occupant behaviors on microbiomes. Built environments, occupants, and microbiomes constitute a system of ecosystems with extensive interactions that impact one another. Understanding the interactions between these systems is essential to develop strategies for effective management of the built environment and its inhabitants to enhance public health and well-being. Numerous studies have been conducted to characterize the microbiomes of the built environment. This review summarizes current progress in understanding the interactions between attributes of built environments and occupant behaviors that shape the structure and dynamics of indoor microbial communities. In addition, this review also discusses the challenges and future research needs in the field of microbiomes of the built environment that necessitate research beyond the basic characterization of microbiomes in order to gain an understanding of the causal mechanisms between the built environment, occupants, and microbiomes, which will provide a knowledge base for the development of transformative intervention strategies toward healthy built environments. The pressing need to control the transmission of SARS-CoV-2 in indoor environments highlights the urgency and significance of understanding the complex interactions between the built environment, occupants, and microbiomes, which is the focus of this review.

关键词： Microbiome     Built Environment     Occupant     Health    

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for preventing peritoneal fibrosis in peritoneal dialysis patients: new insights based on peritoneal inflammation

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 349-358 doi: 10.1007/s11684-017-0571-2

摘要：

Peritoneal dialysis (PD) is an established form of renal replacement therapy. Long-term PD leads to morphologic and functional changes to the peritoneal membrane (PM), which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation and angiogenesis are key events during the pathogenesis of peritoneal fibrosis. This review discusses the pathophysiology of peritoneal fibrosis and recent research progress on key fibrogenic molecular mechanisms in peritoneal inflammation and angiogenesis, including Toll-like receptor ligand-mediated, NOD-like receptor protein 3/interleukin-1β, vascular endothelial growth factor, and angiopoietin-2/Tie2 signaling pathways. Furthermore, novel strategies targeting peritoneal inflammation and angiogenesis to preserve the PM are discussed in depth.

关键词： peritoneal dialysis     peritoneal fibrosis     inflammation     angiogenesis    

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Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

《环境科学与工程前沿（英文）》 2022年 第16卷 第5期 doi: 10.1007/s11783-022-1543-6

摘要：

● Riverine microbiomes exhibited hyperlocal variation within a single transect.

关键词： Microbiome     Freshwater     Taxon accumulation curve     Community assembly    

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Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

《医学前沿（英文）》 2021年 第15卷 第1期   页码 11-32 doi: 10.1007/s11684-019-0731-7

摘要： The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

关键词： microbiome     prostate cancer     prevention     treatment     molecular pathological epidemiology (MPE)     biomarker    

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Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating

《医学前沿（英文）》 2021年 第15卷 第5期   页码 750-766 doi: 10.1007/s11684-021-0839-4

摘要： Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

关键词： particulate matter 2.5     sirtuin 2     p65     airway inflammation     bronchial hyperresponsiveness     triptolide    

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Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

《环境科学与工程前沿（英文）》 2022年 第16卷 第6期 doi: 10.1007/s11783-022-1560-5

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Comparative analysis of impact of human occupancy on indoor microbiomes

《环境科学与工程前沿（英文）》 2021年 第15卷 第5期 doi: 10.1007/s11783-020-1383-1

摘要：

• Exposure to indoor microbiomes is a public health concern in educational facilities.

关键词： Built environment     Indoor microbiome     Occupant     Building     Sequencing    

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Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation

Weijian Hang, Chen Chen, Xin A. Zhang, Dao Wen Wang

《医学前沿（英文）》 2021年 第15卷 第4期   页码 638-643 doi: 10.1007/s11684-021-0831-z

摘要： The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

关键词： COVID-19     endothelial dysfunction     inflammation reaction     cytokine storm    

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Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

《医学前沿（英文）》 2019年 第13卷 第4期   页码 471-481 doi: 10.1007/s11684-019-0686-8

摘要： Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus . Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics     tacrolimus     glucose disorders     microbiome    

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微生物组分析技术的发展趋势：从单细胞功能成像到菌群大数据

徐健, 马波, 苏晓泉, 黄适, 徐欣, 周学东, 黄巍, Rob Knight

《工程（英文）》 2017年 第3卷 第1期   页码 66-70 doi: 10.1016/J.ENG.2017.01.020

摘要：

方法学创新一直是微生物组学研究的核心驱动力。我们认为在未来五到十年，微生物组的方法学体系在研究理念与技术平台方面将发生三大变革：①从监测菌群“结构”变化向监测菌群“功能/状态”变化的变革；②从细胞“群体”分析精度向细胞“个体”分析精度的转变；③从“数据分析”向“数据科学”的跨越。在这里我们针对实现上述三大方法学变革需要克服的关键科学或技术挑战，重点介绍了部分中国微生物组分析方法学研究团队及其国际合作伙伴的最新工作进展。我们相信中国微生物组计划应把握住当前这一重要机遇，通过在微生物组分析方法学前沿开展富有雄心、远见、创意与竞争力的交叉合作研究，为国际微生物组计划贡献一系列“中国制造”的新方法、新工具和新仪器。

关键词： 微生物组     方法学创新     单细胞分析     大数据     中国微生物组计划    

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标题 作者 时间 类型 操作

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

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

期刊论文

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

期刊论文

Cytokines and inflammation in adipogenesis: an updated review

Ning Jiang, Yao Li, Ting Shu, Jing Wang

期刊论文

Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

期刊论文

Appendiceal inflammation affects the length of stay following appendicectomy amongst children: a myth

null

期刊论文

Understanding building-occupant-microbiome interactions toward healthy built environments: A review

Shuai Li, Zhiyao Yang, Da Hu, Liu Cao, Qiang He

期刊论文

for preventing peritoneal fibrosis in peritoneal dialysis patients: new insights based on peritoneal inflammation

null

期刊论文

Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

期刊论文

Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

期刊论文

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating

期刊论文

Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome

期刊论文

Comparative analysis of impact of human occupancy on indoor microbiomes

期刊论文

Endothelial dysfunction in COVID-19 calls for immediate attention: the emerging roles of the endothelium in inflammation

Weijian Hang, Chen Chen, Xin A. Zhang, Dao Wen Wang

期刊论文

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

期刊论文

微生物组分析技术的发展趋势：从单细胞功能成像到菌群大数据

徐健, 马波, 苏晓泉, 黄适, 徐欣, 周学东, 黄巍, Rob Knight

期刊论文