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肠道菌群 3

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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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Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2019年 第13卷 第4期   页码 461-470 doi: 10.1007/s11684-019-0695-7

摘要： The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal–luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in which is a butyrate-producing genera of bacteria, and a significant increase in in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to and may serve as a promising biomarker for the early detection of CRC.

关键词： colorectal cancer (CRC)     gut microbiota     intestinal     Eubacterium     Devosia    

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Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels

LIN Ji, YAN Guangtao, HAO Xiuhua, ZHANG Kai, GAO Xiaoning, LIAO Jie

《医学前沿（英文）》 2007年 第1卷 第1期   页码 87-92 doi: 10.1007/s11684-007-0017-3

摘要： The aim of this paper is to explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and to examine the roles of leptin and orexin-A in acute inflammatory responses. An intestinal I/R injury model of rats was made; the rats were grouped according to the time of after 60 min ischemia. Radioimmunoassay was employed to detect the levels of leptin in serum and adipose tissue and orexin-A levels in plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was used to detect mRNA expressions of adipose leptin and hypothalamus orexin-A. Compared with the levels before the injury, serum leptin in 60 min ischemia/30 min reperfusion (I60´R30´) group decreased and that of I60´R360´ group increased. Compared with sham-operation group (sham group) after injury, serum leptin level of I60´R360´ group increased, adipose leptin levels of I60´R30´ and I60´R90´ decreased, and adipose leptin in I60´R360´ group increased. After the injury, adipose leptin mRNA expressions of I60´R30´, I60´R240´ and I60´R360´ increased, whereas that of I60´R150´ group decreased as compared with the sham group. There was no significant difference in the protein levels of orexin-A, either between plasma and hypothalamus or between pre- and post-I/R injury. Compared with sham group, hypothalamus orexin-A mRNA expressions of I60´R30´ and I60´R90´ decreased gradually after the injury, with that of I60´R150´ group reaching the lowest, and those of I60´R240´ and I60´R360´ recovering gradually, although they were still significantly lower than that of sham group. Leptin and orexin-A respond to intestinal I/R injury in a time-dependent manner, with leptin responding more quickly than orexin-A does, and both of them may contribute to the metabolic disorders in acute inflammation.

关键词： significant difference     intestinal I/R     transcriptase-polymerase     metabolic     central secretory    

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Structural shifts in the intestinal microbiota of rats treated with cyclosporine A after orthotropic

Junjun Jia, Xinyao Tian, Jianwen Jiang, Zhigang Ren, Haifeng Lu, Ning He, Haiyang Xie, Lin Zhou, Shusen Zheng

《医学前沿（英文）》 2019年 第13卷 第4期   页码 451-460 doi: 10.1007/s11684-018-0675-3

摘要： Understanding the effect of immunosuppressive agents on intestinal microbiota is important to reduce the mortality and morbidity from orthotopic liver transplantation (OLT). We investigated the relationship between the commonly used immunosuppressive agent cyclosporine A (CSA) and the intestinal microbial variation in an OLT model. The rat samples were divided as follows: (1) N group (normal control); (2) I group (isograft LT, Brown Norway [BN] rat to BN); (3) R group (allograft LT, Lewis to BN rat); and (4) CSA group (R group treated with CSA). The intestinal microbiota was assayed by denaturing gradient gel electrophoresis profiles and by using real-time polymerase chain reaction. The liver histopathology and the alanine/aspartate aminotransferase ratio after LT were both ameliorated by CSA. In the CSA group, the numbers of rDNA gene copies of cluster I, cluster XIV, and Enterobacteriaceae decreased, whereas those of increased compared with the R group. Cluster analysis indicated that the samples from the N, I, and CSA groups were clustered, whereas the other clusters contained the samples from the R group. Hence, CSA ameliorates hepatic graft injury and partially restores gut microbiota following LT, and these may benefit hepatic graft rejection.

关键词： microbial community     liver transplantation     immunosuppressive agents     cyclosporine A    

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具有泵送控释性能的肠靶向Janus型双腔室海藻酸钙基微胶囊 Article

温霜, 巨晓洁, 刘文英, 刘玉琼, 蒲兴群, 刘壮, 汪伟, 谢锐, Yousef Faraj, 褚良银

《工程（英文）》 2023年 第24卷 第5期   页码 114-125 doi: 10.1016/j.eng.2022.05.021

摘要：

本文成功开发了一种具有泵送控释特性的θ形双腔室肠靶向海藻酸钙基微胶囊，囊壁为海藻酸钙-壳聚糖/精蛋白/二氧化硅（ACPSi）复合壳，为封装的药物在胃环境中提供了良好保护，实现药物的肠靶向释放。该θ形微胶囊由含药室和助推室两个腔室组成：含药室负载疏水药物吲哚美辛，其囊壁内嵌肠溶性
羟丙甲基纤维素邻苯二甲酸酯（HPMCP）微球，作为“微阀门”（micro-valves）；助推室包封助推剂聚丙烯酸（PAA），在肠液环境中，PAA发生溶胀，可提高吲哚美辛释放速率。结果显示，载药的θ-ACPSi 微胶囊在模拟胃液（pH值为2.5）中，吲哚美辛的释放率小于1%。然而，进入模拟肠液（pH值为6.8）时，含药室囊壁中的HPMCP微球溶解，释药“微通道”（microchannel）被打开，同时助推室中的PAA发生溶胀，为药物的释放提供推动力。结果，吲哚美辛在小肠中以恒定的速度释放60%以上。因此，该θ-ACPSi 微胶囊具有良好的泵送和肠靶向控释性能，为口服肠道靶向给药系统的开发提供了一种新策略。

关键词： 微胶囊     海藻酸钙     肠靶向递送     泵送性能     控制释放    

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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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compound Sophorae Flavescentis Jiechangrong capsule on expression of NF-κB p65 and STAT6 in the intestinal

Heng FAN MD, Jia ZHAO MM, Lin SHEN BM, Qing TANG MD, Zhexin SHOU MM, Li LIANG BM, Yi LIAO BM, Xiaoyan CHEN BM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 480-484 doi: 10.1007/s11684-009-0083-9

摘要： The effects of compound Sophorae Flavescentis Jiechangrong capsule (CSFJC) on the expression of nuclear factor-κB p65 (NF-κB p65) and signal transducer and activator of transcription 6 (STAT6) in the intestinal mucosa of patients with ulcerative colitis and the possible mechanism were investigated. Eighteen patients with ulcerative colitis were randomly divided into a traditional Chinese medicine (TCM) group ( = 11) treated by CSFJC and a western medicine (WM) group ( = 7) treated by Sulfasalazine tablets. The treatment duration lasted eight weeks. Before and after the treatment, the symptoms and the physical signs were observed, and the routine stool test, the colonoscopy, and pathological examination were performed in the two groups. The expression levels of NF-κBp65 and STAT6 were detected by using immunohistochemistry. The results showed that the total effective rate of the curative effectiveness in TCM and WM groups was 100% and 71.4%, respectively, and the total effective rate of colonic mucosa lesion in TCM and WM groups was 90.9% and 71.4%, respectively, with the differences being significant (all < 0.05). The total effective rate of syndromes of damp-heat blocking according to the TCM in TCM and WM groups was 90.9% and 71.4%, respectively. After the treatment, the expression of NF-κB p65 and STAT6 in the two groups was decreased, and the decrease of NF-κB p65 and STAT6 expression in TCM group was more significant than in WM group ( < 0.05). It was concluded that CSFJC can inhibit the activation and expression of NF-κB p65 and STAT6 in the intestinal mucosa of patients with ulcerative colitis, which is a possible mechanism for CSFJC treating ulcerative colitis.

关键词： colitis     ulcerative     compound Sophorae Flavescentis Jiechangrong capsule     nuclear factor-κ     B p65 (NF-κ     B p65)     signal transducer and activator of transcription 6 (STAT6)    

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Endoscopic resection of a huge Brunner's gland adenoma

ZHANG Binbin, REN Xu, TANG Xiufen, CHI Yuxin, SHI Xuesong

《医学前沿（英文）》 2008年 第2卷 第4期   页码 414-418 doi: 10.1007/s11684-008-0080-4

摘要： Brunner’s gland adenoma is a rare tumour of the duodenum, which is usually benign. A 71-year-old woman presenting with epigastric pain, upper gastrointestinal haemorrhage and melaena was reported in this paper. Upper gastro-intestinal (GI) endoscopy revealed a large pedunculated tumour on the superior part of the duodenal bulb. Endoscopic polypectomy was successfully performed by clipping and nylon thread without any complications. Histological examination revealed a Brunner’s gland adenoma.

关键词： superior     Histological examination     endoscopy     gastro-intestinal     gastrointestinal haemorrhage    

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肠道优势菌群丰度变化与COVID-19严重程度相关性的临床意义 Article

汤灵玲,顾思岚,龚忆雯,李博,鲁海峰,李强,张如洪,高翔,吴正洁,张佳颖,张园园,李兰娟

《工程（英文）》 2020年 第6卷 第10期   页码 1178-1184 doi: 10.1016/j.eng.2020.05.013

摘要：

新冠病毒肺炎（COVID-19）是一种高度传染性疾病。与H7N9感染相似，COVID-19的典型临床表现是肺炎和细胞因子风暴。我们在既往研究中观察到H7N9患者存在肠道菌群失调。然而，肠道微生物菌群与COVID-19之间的关系尚未明确。本研究共纳入了57名COVID-19患者，其中包括20例普通型、19例重型以及18例危重型。本研究的目的是利用定量聚合酶链反应（q-PCR），研究COVID-19患者的10种主要肠道优势菌群的丰度变化，从而建立这些菌群与COVID-19临床指标之间的相关性。结果表明，COVID-19患者的10种主要肠道菌群丰度出现变化，这些肠道微生物菌群的变化与疾病严重程度和血液学指标有关。产丁酸菌，如普拉梭菌（Faecalibacterium prausnitzii）、酪酸梭菌（Clostridium butyricum）、柔嫩梭菌（Clostridium leptum）、直肠真杆菌（Eubacterium rectale）的丰度显著降低，细菌群落的这些变化有助于区分危重型与普通型和重型患者。此外，常见的条件致病菌肠球菌（Enterococcus, Ec）和肠杆菌科细菌（Enterobacteriaceae, E）的丰度在COVID-19患者中增加，尤其对于预后较差的危重型患者。这些结果表明，这些肠道优势菌群可作为COVID-19的诊断生物标志物，并且Ec/E值可用于预测危重型患者预后。

关键词： 肠道菌群     新冠病毒肺炎（COVID-19）     严重急性呼吸系统综合征冠状病毒2 （SARS-CoV-2）    

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Effect of salvia miltiorrhiza pretreatment on the CCK and VIP expression in hepatic ischemia-reperfusion-induced digestive tract congestion

Zhi-Yong ZHANG, Xiao-Ping CHEN, Qi-Ping LU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 317-322 doi: 10.1007/s11684-010-0035-4

摘要： The inhibitory effect of different reperfusion periods 45 min following hepatic ischemia on the expression of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the jejunum and the effect of salvia miltiorrhiza pretreatment were investigated, and the possible mechanism and implications were explored. Eighty rats were randomly divided into four groups: normal control group (CO group), sham-operated group (SO group), ischemia/reperfusion (I/R) injury group (IR group) and salvia miltiorrhiza pretreatment group (SM group). The rat model of I/R was established by using a non-invasive artery clamp to clip (45 min) or relax the hepatic pedicle. In the SM group, saline (40 mL/kg) and salvia miltiorrhiza injection (6 g/kg) were injected via the tail vein 30 min before clipping the hepatic pedicle. In the SO group only the porta hepatis was dissected after laparotomy without clamping the hepatic pedicle. At 0, 3, 12, 24 and 72 h post-reperfusion, respectively, upper jejunum samples were taken for immunohistochemistry of CCK and VIP. It was found that 0 h after I/R, the expression of CCK and VIP in the upper jejunum was upregulated. With prolongation of the reperfusion period, the expression of CCK and VIP was also increased, reached the peak at the 24th h, and gradually returned to the normal level at the 72nd h after reperfusion. The levels of both CCK and VIP in the SM group were lower than those in the IR group. It is suggested that the digestive tract congestion injury caused by liver ischemia can upregulate the expression of CCK and VIP in the jejunum following reperfusion. Salviae pretreatment can partly reduce the increased expression of CCK and VIP in the jejunum in the same period, which might contribute to the early recovery of gastrointestinal motility.

关键词： hepatic ischemia-reperfusion     digestive tract congestion     cholecystokinin     vasoactive intestinal peptide     salvia miltiorrhiza    

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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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植物化学物质的生物功能及其在家畜中的应用研究——以Nrf2/Keap1系统为目标

覃思, 侯德兴

《工程（英文）》 2017年 第3卷 第5期   页码 738-752 doi: 10.1016/J.ENG.2017.03.011

摘要：

活性氧（ROS）对人类和其他动物健康的负面影响非常值得关注。ROS可能由机械伤害、热刺激、感染和化学刺激产生。核转录相关因子（Nrf2）及其伴侣蛋白Keap1组成的Nrf2/Keap1系统在抗氧化作用中扮演着重要角色。Nrf2/Keap1系统通过与抗氧化反应元件（ARE）相互作用，调控一系列解毒酶和抗氧化酶基因的表达来维持机体氧化还原的平衡状态。膳食植物化学物质在蔬菜、水果、谷物和草药中普遍存在，研究发现其有益健康，还可通过多种途径调节Nrf2介导的II相酶来提高家畜的生长性能和肉质。然而，关于植物化学物质作用效果的大量数据有些混乱，需要根据植物化学物质的功能和作用机制进行相应的分类。在本文中，我们首先介绍了植物化学物质的抗氧化性及其与Nrf2/Keap1系统的关系，并总结了植物化学物质通过靶向Nrf2/Keap1系统，对家畜生长性能、肉质和肠道菌群的影响。这些详尽的数据有助于阐述植物化学物质在家畜中潜在的生物功能特性。

关键词： 植物化学物质     生物功能     Nrf2/Keap1 系统     生长性能     肉质     肠道菌群    

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一种基于Caco-2细胞单层膜的筛选抵抗特定代谢性疾病益生菌的模型 Article

刘阳, 彭江, 朱诗雅, 于雷雷, 田丰伟, 赵建新, 张灏, 陈卫, 翟齐啸

《工程（英文）》 2023年 第25卷 第6期   页码 222-233 doi: 10.1016/j.eng.2022.02.014

摘要：

最近的研究揭示了益生菌在缓解与肠道屏障功能障碍相关的代谢疾病方面的潜力。然而，目前还没有一种能高效筛选抵抗特定代谢疾病益生菌菌株的模型。本研究采用肿瘤坏死因子（TNF-α）和酒精处理的Caco-2细胞单层膜模型，评价了139株乳杆菌在体外对肠道屏障功能的影响。然后，我们选择了11株对肠道屏障具有不同调节能力的乳杆菌菌株，进一步在体内评价了它们对卵巢切除引起的骨质疏松症或慢性酒精性肝损伤的作用效果。体外细胞模型和体内动物模型数据的关联性分析显示，两种疾病模型下的Pearson系数分别为0.82和－0.97，表明使用体外细胞模型模拟益生菌在体内的保护作用是可靠的。本研究建立了一种基于Caco-2细胞单层膜模型的体外方法，用于高效筛选可以抵抗特定代谢疾病（如骨质疏松症和慢性酒精性肝病）的益生菌。

关键词： 乳杆菌     肠道屏障     Caco-2细胞     筛选模型     代谢性疾病    

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通过原位观察揭示人体肠道微生物组的重建和动态变化 Article

刘小林, 戴敏, Yue Ma, 赵娜, Ziyu Wang, Ying Yu, Yakun Xu, Huijie Zhang, Liyuan Xiang, He Tian, 税光厚, 张发明, 王军

《工程（英文）》 2022年 第15卷 第8期   页码 89-101 doi: 10.1016/j.eng.2021.03.015

摘要：

人体肠道微生物组主要通过使用粪便样本进行研究，这种做法已经得到了关于胃肠道微生物群落的组成和功能的重要知识。然而，这种对粪便材料的依赖限制了对胃肠道其他位置（原位）微生物动力学的研究，并且粪便样本不能随时获得，这也阻碍了在更精细的时间尺度（如小时）下进行分析。在我们的研究中，我们利用结肠途径经内镜肠内导管（一种最初为粪便微生物群移植开发的技术）每天两次对回盲部微生物组进行采样；然后对这些样品进行宏基因组和宏转录组学分析。从5 名健康志愿者身上共收集了43 份回盲部样本及28 份尿液和粪便样本。在5 名志愿者中分析的回盲部和粪便微生物组被发现在宏基因组分析中相似，但它们的活性基因（宏转录组）被发现高度不同。两种微生物组在泻药暴露后都受到干扰；随着时间的推移，它们表现出与治疗前状态的差异减少，从而证明了作为肠道微生物组的先天特性——恢复力，尽管它们在我们的观察时间窗口内没有完全恢复。白天和夜间对回盲部微生物组的采样显示，在一系列细菌种类和功能途径中存在昼夜节律，特别是与短链脂肪酸产生相关的细菌，如痤疮丙酸杆菌和辅酶A生物合成II。自相关分析和波动分解进一步表明了昼夜振荡的显著周期性。粪便和尿液样本中的代谢组学分析反映出了肠道微生物组的扰动和恢复，表明肠道微生物组对参与宿主健康的诸多关键代谢物的重要贡献。这项研究为人体肠道微生物组及其内在恢复力和昼夜节律以及这些对宿主的潜在后果提供了新的见解。

关键词： 昼夜节律     重建     宏基因组     宏转录组     代谢组     经内窥镜肠管    

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基于系统发育和比较基因组分析揭示与发酵乳杆菌缓解结肠炎相关的关键基因 Article

赵岩, 张程程, 于雷雷, 田丰伟, 赵建新, 张灏, 陈卫, 翟齐啸

《工程（英文）》 2022年 第17卷 第10期   页码 170-182 doi: 10.1016/j.eng.2020.09.016

摘要：

越来越多的研究表明，发酵乳杆菌可以用于溃疡性结肠炎的预防和治疗。本研究中，我们从中国不同地区的人群粪便样本中分离出了105 株发酵乳杆菌，并对其基因组草图进行了测序。我们分析了这些菌株的泛基因组和系统发育特征，并对4 个模型菌株（发酵乳杆菌3872、CECT5716、IFO3956 和VRI003）也进行了分析。系统发育分析表明，发酵乳杆菌基因组的进化方向与宿主的地理位置、性别、族群和年龄没有明显的关系。我们挑选了3 株来自不同的系统发育支系的发酵乳杆菌（FWXBH115、FGDLZR121和FXJCJ61）和发酵乳杆菌模式菌株CECT5716，通过构建右旋糖酐硫酸钠（DSS）诱导的结肠炎小鼠模型，
探究这几株菌的抗炎和免疫调节活性。发酵乳杆菌FXJCJ61 和CECT5716 可以通过缓解所有结肠炎相关的组织学指标，保护黏膜完整性，增加肠道短链脂肪酸（SCFA），显著减轻结肠炎，而其他两株菌未能提供类似的保护作用。发酵乳杆菌FXJCJ61 和CECT5716 的抗炎机制与核转录因子kappa-B（NF-κB）信号通路激活以及促进白细胞介素10（IL-10）的产生有关。比较基因组分析结果表明，这些有益发酵乳杆菌的抗炎作用可能与一些特定基因有关。

关键词： 发酵乳杆菌     结肠炎     抗炎     系统发育分析     比较基因组分析    

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