肠道微生物菌群分型的研究进展

人体肠道内存在着处于动态平衡中的复杂微生物群体,包含1000多种细菌和古生菌等共生微生物。它们广泛参与人体的营养、代谢和免疫等生理过程,是影响健康最重要的因素之一。同一个体不同胃肠道部位的微生物群落组成显著不同,而在不同个体的肠道微生物群落组成也存在很大差异。肠道微生物群落结构受到饮食习惯、药物干预以及生活环境等因素影响,形成了不同个体间菌群组成的差异。通过菌群测序分析和群体分型,可以将不同个体的肠道微生物群落组成分为拟杆菌、普氏菌和瘤胃球菌三种肠型。确定肠道微生物群落结构的分型,将复杂的肠道微生物系统模式化,有利于对大样本肠道微生物菌群进行分析,更好地指导相关疾病的诊断和治疗。本文综述了肠道微生物的分型和相关影响因素的进展。     

肠道菌群与孤独症谱系障碍儿童功能性便秘的关系

目的 探讨孤独症谱系障碍（autism spectrum disorder,ASD）儿童肠道菌群组成与功能性便秘之间的关系,为该类患者的治疗提供参考。方法 选择101例2～7岁ASD儿童和82例年龄、性别相匹配健康儿童为研究对象,采用罗马Ⅳ标准评估便秘,将所有儿童分为ASD便秘组（ASD constipated,AD-C）、ASD非便秘组（ASD non-constipated,AD-NC）、正常便秘组（neurotypical constipated,NT-C）、正常非便秘组（neurotypical non-constipated,NT-NC）。对所有粪便样本中细菌16S rRNA基因V3-V4高变区进行测序,检测肠道菌群。结果 与NT组相比,AD组儿童肠道菌群α多样性指数（Chao1）显著升高（t=2.258,P=0.006）,组间β多样性差异有统计学意义（R=0.210,P<0.001）。AD组儿童肠道优势菌群为双歧杆菌属、柯林斯菌属、脱硫弧菌属等。与NT-NC组相比,AD-NC组患儿肠道菌群Chao1指数显著升高（t=2.170,P=0.021）,组间β多样性差异有统计...     

肠道微生物与线粒体之间的互作

肠道微生物与肠道细胞线粒体功能之间的关系十分密切。一方面,肠道微生物可直接或通过短链脂肪酸、硫化氢和一氧化氮等代谢产物间接影响与线粒体相关的能量代谢过程,调节线粒体活性氧的产生,调控线粒体甚至整个机体的免疫反应。另一方面,肠道细胞线粒体功能紊乱和基因组的遗传变异也会影响肠道微生物的组成和功能。本文主要介绍了肠道微生物和线粒体之间的互作关系的最新研究进展,为靶向作用于肠道菌群和线粒体以调节肠道健康提供理论依据。     

昆虫肠道微生物的研究进展和应用前景

昆虫肠道的独特结构和理化性质为多种多样的微生物定殖提供了特殊环境,肠道微生物的群落组成与宿主昆虫的生长发育、代谢繁殖等生命活动密切相关。种类丰富多样、生态位分布广泛的昆虫体内含有大量特化的肠道微生物群落,经过长期协同进化形成的共生关系具有多方面无可替代的优势。这种相对稳定的共生关系对昆虫整个生命周期具有极其重要的作用,肠道微生物不仅为宿主提供重要的营养物质、协助消化食物、提高宿主防御和解毒能力,还影响宿主昆虫的寿命、发育周期以及交配与繁殖能力等。同时,昆虫肠道微生物在农业、生态、医药以及能源环保等多个学科领域也显示出了巨大的应用前景。本文就昆虫肠道微生物群落的多样性、功能和影响肠道微生物生存因素,以及应用前景等方面进行综述,讨论了昆虫肠道微生物的最新研究进展。     

微生物组学与肠道肿瘤

肠道肿瘤的发病是宿主、环境等多因素共同作用的结果。宿主与其体内生活的肠道微生物有着密不可分的互利共生关系。随着高通量测序等研究技术的进一步成熟,肠道微生态的功能、组成以及与肠道肿瘤发生、发展、诊治间的关系日趋明朗。确定的和肿瘤相关微生物的异质性可能被开发为筛选肠道肿瘤风险的有力工具,而对菌群的干预和改变可能成为肠道肿瘤预防和治疗策略的重要环节之一。     

肠道菌群代谢物对甲酚和对乙酚与孤独症谱系障碍的相关性及其潜在致病机制

孤独症谱系障碍(autism spectrum disorder, ASD)是一类患病率高且病因复杂的神经发育障碍性疾病，患者主要特征为社会交往与交流障碍并表现出兴趣狭窄与重复刻板行为。临床证据表明肠道菌群失衡普遍存在于ASD患者群体中并参与ASD的发病，但其中机制还有待明确。近期研究发现肠道菌群可能间接通过其代谢产物影响ASD的发展。本综述将重点阐述两种肠道菌群代谢物——对甲酚和对乙酚与ASD之间的相关性及其潜在致病机制，以期发掘肠道菌群在ASD发病过程中的潜在作用与机理，并为ASD的诊断与治疗提供新思路。     

孤独症谱系障碍与胃肠道疾病研究进展

孤独症谱系障碍(autistic spectrum disorder,ASD)是指一系列的神经系统发育障碍,根据美国《精神障碍诊断和统计手册》(第五版)(DSM-5),其主要特征为社会交往和交流障碍、重复和刻板行为。随着对该疾病的深入了解,发现ASD儿童存在多系统的共患疾病,其中最常见的就是ASD儿童广泛存在的胃肠道症状(gastrointestinal issues,GI),如腹痛、腹泻、呕吐、慢性便秘和胃食管反流等。胃肠道疾病严重影响ASD儿童的饮食、睡眠和日常行为。事实上,部分ASD儿童的一些行为问题(如自我伤害、易激惹等)与胃肠道疾病有密切的关系。因此,ASD儿童的胃肠道疾病引起了父母和研究者越来越多的关注。同时,肠-脑轴的作用、肠道菌群失调可能造成的影响也受到关注。本文综述了ASD与胃肠道疾病的新近研究进展,介绍了ASD儿童胃肠道疾病的临床表现及其可能的原因,展望了通过治疗胃肠道疾病、调整肠道菌群对改善ASD儿童生理健康和行为症状的意义。     

肠道微生物及益生菌治疗对2型糖尿病的影响

2型糖尿病(type 2 diabetes mellitus,T2DM)是严重影响人类身体健康和生活质量的慢性疾病。研究发现其与肠道微生物的组成密切相关。随着目前肠道微生物的作用受到广泛关注,我们对2型糖尿病患者肠道菌群的变化有了更深入了解,许多功能强大的有益菌如阿克曼氏菌、柔嫩梭菌被发现,并发现由多种厌氧菌产生的不同短链脂肪酸对2型糖尿病患者的有益影响。补充有益菌和摄入益生菌制剂等通过调节肠道微生物群可能对预防和治疗2型糖尿病有效,但由于肠道微生物的复杂性和益生菌的局限性,需要进一步研究来评估益生菌的最佳剂量反应效应,并应用多组学方法提高基于微生物干预的个性化治疗,缓解和治疗2型糖尿病等代谢疾病。     

仔猪肠道微生物研究进展

肠道菌群在哺乳动物及人类健康的作用正日益受到重视。仔猪的健康生长需要一个动态平衡的肠道微生态环境。然而,在猪的生命周期中,从食管到直肠的微生物分布与组成存在时间和空间的变化。健康的肠道菌群具有促进猪的营养代谢,维持肠黏膜屏障,调节免疫应答,抑制病原菌感染等功能。多种因素对猪肠道菌群的形成与稳定具有重要的作用,包括分娩方式(经过产道或剖宫产)、幼龄时期饮食(母乳或配方饲料)、抗生素或抗生素样分子的使用等。本文主要从仔猪肠道微生物组成与定植、功能、影响肠道微生物的因素等方面论述了仔猪肠道微生物与仔猪肠道健康的关系,从而加深肠道微生物对维护仔猪肠道健康作用的认识。     

肠道微生态与白血病的研究进展

微生物群与人体的健康密切相关,约20%的恶性肿瘤与微生态失调有关。研究显示肠道微生物可以调节造血,其与血液系统疾病的关系逐渐得到研究者的关注,肠道微生物参与白血病的发生发展,影响白血病的治疗效果。较早的暴露于微生物群是儿童白血病的保护性因素,化疗会引起肠道微生物紊乱,肠道微生物可以改变化疗药物的疗效和毒性,其多样性和组成能够预测化疗相关的并发症,通过微生态制剂和粪菌移植可以减少化疗相关的并发症。本文从肠道微生态与白血病及其并发症的关系,以及调节肠道微生态对白血病的影响两个方面的最新进展进行综述。     

Correlation of Gut Microbiome Between ASD Children and Mothers and Potential Biomarkers for Risk Assessment

Variation of maternal gut microbiota may increase the risk of autism spectrum disorders(ASDs) in offspring. Animal studies have indicated that maternal gut microbiota is related to neurodevelopmental abnormalities in mouse offspring, while it is unclear whether there is a correlation between gut microbiota of ASD children and their mothers. We examined the relationships between gut microbiome profiles of ASD children and those of their mothers, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. Gut microbiome was profiled and evaluated by 16S ribosomal RNA gene sequencing in stool samples of 59 mother–child pairs of ASD children and 30 matched mother–child pairs of healthy children. Significant differences were observed in the gut microbiome composition between ASD and healthy children in our Chinese cohort. Several unique bacterial biomarkers, such as Alcaligenaceae and Acinetobacter, were identified. Mothers of ASD children had more Proteobacteria, Alphaproteobacteria, Moraxellaceae, and Acinetobacter than mothers of healthy children. There was a clear correlation between gut microbiome profiles of children and their mothers; however, children with ASD still had unique bacterial biomarkers, such as Alcaligenaceae, Enterobacteriaceae, and Clostridium. Candidate biomarkers discovered in this study had remarkable discriminatory power. The identified patterns of mother–child gut microbiome profiles may be important for assessing risks during the early stage and planning of personalized treatment and prevention of ASD via microbiota modulation.     

肠道菌群及其代谢产物 与结肠腺瘤性息肉相关性的研究进展

结肠癌(colorectal cancer,CRC)是常见的消化道恶性肿瘤,其发病率和病死率都极高。从结肠息肉发展到结肠癌一般需要10～15年,且大多遵循息肉-腺瘤-癌症的发展过程,结肠腺瘤性息肉(colorectal adenomatous polyps,CAP)被认为是结肠癌的癌前病变。有研究显示肠道菌群的改变与肠道腺瘤性息肉样变及癌症的发生发展有密切的相关性。根据肠道菌群在不同病理状态下的富集程度,可以进一步分析其与结肠病变之间的关系。本文就肠道菌群的构成,CAP患者粪便和腺瘤组织中肠道菌群富集的改变,以及肠道菌群代谢产物对CAP患者的影响等内容进行综述,为结肠腺瘤性息肉的早期诊断和治疗提供依据。     

Microbiota-gut-brain axis in autism spectrum disorder

Extensive studies, largely during the past decade, identify the dynamic and bidirectional interaction between the bacteria resident in the intestines and their host brain along the "microbiota-gut-brain axis". This interaction modulates the development and function of the central nervous system and is implicated in neurological disorders. As a neurodevelopmental disorder, autism spectrum disorder (ASD) is considered a historically defect in the brain. With accumulating evidence showing how the microorganisms modulate neural activities, more and more research is focusing on the role of the gut microbiota in mitigating ASD symptoms and the underlying mechanisms. In this review, we describe the intricate and crucial pathways via which the gut microbiota communicates with the brain, the microbiota-gut-brain axis, and summarize the specific pathways that mediate the crosstalk of the gut microbiota to the brain in ASD.     

Gut microbiota in patients after surgical treatment for colorectal cancer

Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.     

The Microbiota‐Inflammasome Hypothesis of Major Depression

We propose the “microbiota‐inflammasome” hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long‐lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro‐inflammatory pathways mediated by the Nod‐like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress‐induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive‐like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co‐morbid conditions. A number of testable predictions surface from this microbiota‐gut‐inflammasome‐brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.     

Intestinal microbiota composition in fishes is influenced by host ecology and environment

The digestive tracts of vertebrates are colonized by complex assemblages of micro-organisms, collectively called the gut microbiota. Recent studies have revealed important contributions of gut microbiota to vertebrate health and disease, stimulating intense interest in understanding how gut microbial communities are assembled and how they impact host fitness (Sekirov et al. 2010). Although all vertebrates harbour a gut microbiota, current information on microbiota composition and function has been derived primarily from mammals. Comparisons of different mammalian species have revealed intriguing associations between gut microbiota composition and host diet, anatomy and phylogeny (Ley et al. 2008b). However, mammals constitute <10% of all vertebrate species, and it remains unclear whether similar associations exist in more diverse and ancient vertebrate lineages such as fish. In this issue, Sullam et al. (2012) make an important contribution toward identifying factors determining gut microbiota composition in fishes. The authors conducted a detailed meta-analysis of 25 bacterial 16S rRNA gene sequence libraries derived from the intestines of different fish species. To provide a broader context for their analysis, they compared these data sets to a large collection of 16S rRNA gene sequence data sets from diverse free-living and host-associated bacterial communities. Their results suggest that variation in gut microbiota composition in fishes is strongly correlated with species habitat salinity, trophic level and possibly taxonomy. Comparison of data sets from fish intestines and other environments revealed that fish gut microbiota compositions are often similar to those of other animals and contain relatively few free-living environmental bacteria. These results suggest that the gut microbiota composition of fishes is not a simple reflection of the micro-organisms in their local habitat but may result from host-specific selective pressures within the gut (Bevins & Salzman 2011).     

Combined hormonal contraceptives are associated with minor changes in composition and diversity in gut microbiota of healthy women

Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC-related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre-menopausal women using the CHC pill, compared to the control group of nine age-matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive-related changes of the gut microbiota and the potential implications of these changes for women's health.     

Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing

Although pelvic irradiation is effective for the treatment of various cancer types, many patients who receive radiotherapy experience serious complications. Gut microbial dysbiosis was hypothesized to be related to the occurrence of radiation-induced complications in cancer patients. Given the lack of clinical or experimental data on the impact of radiation on gut microbiota, a prospective observational study of gut microbiota was performed in gynecological cancer patients receiving pelvic radiotherapy. In the current study, the overall composition and alteration of gut microbiota in cancer patients receiving radiation were investigated by 454 pyrosequencing. Gut microbial composition showed significant differences (P < 0.001) between cancer patients and healthy individuals. The numbers of species-level taxa were severely reduced after radiotherapy (P < 0.045), and the abundance of each community largely changed. In particular, the phyla Firmicutes and Fusobacterium were significantly decreased by 10% and increased by 3% after radiation therapy, respectively. In addition, overall gut microbial composition was gradually remolded after the full treatment course of pelvic radiotherapy. In this set of cancer patients, dysbiosis of the gut microbiota was linked to health status, and the gut microbiota was influenced by pelvic radiotherapy. Although further studies are needed to elucidate the relationship between dysbiosis and complications induced by pelvic radiotherapy, the current study may offer insights into the treatment of cancer patients suffering from complications after radiation therapy.     

Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome

The gut microbiota is increasingly considered as a symbiotic partner for the maintenance of health. The homeostasis of the gut microbiota is dependent on host characteristics (age, gender, genetic background...), environmental conditions (stress, drugs, gastrointestinal surgery, infectious and toxic agents...). Moreover, it is dependent on the day-to-day dietary changes. Experimental data in animals, but also observational studies in obese patients, suggest that the composition of the gut microbiota is a factor characterizing obese versus lean individuals, diabetic versus non diabetic patients, or patients presenting hepatic diseases such as non alcoholic steatohepatitis. Interestingly, the changes in the gut microbes can be reversed by dieting and related weight loss. The qualitative and quantitative changes in the intake of specific food components (fatty acids, carbohydrates, micronutrients, prebiotics, probiotics), have not only consequences on the gut microbiota composition, but may modulate the expression of genes in host tissues such as the liver, adipose tissue, intestine, muscle. This in turn may drive or lessen the development of fat mass and metabolic disturbances associated with the gut barrier function and the systemic immunity. The relevance of the prebiotic or probiotic approaches in the management of obesity in humans is supported by few intervention studies in humans up to now, but the experimental data obtained with those compounds help to elucidate novel potential molecular targets relating diet with gut microbes. The metagenomic and integrative metabolomic approaches could help elucidate which bacteria, among the trillions in human gut, or more specifically which activities/genes, could participate to the control of host energy metabolism, and could be relevant for future therapeutic developments.     

Habitat fragmentation is associated with dietary shifts and microbiota variability in common vampire bats

Host ecological factors and external environmental factors are known to influence the structure of gut microbial communities, but few studies have examined the impacts of environmental changes on microbiotas in free‐ranging animals. Rapid land‐use change has the potential to shift gut microbial communities in wildlife through exposure to novel bacteria and/or by changing the availability or quality of local food resources. The consequences of such changes to host health and fitness remain unknown and may have important implications for pathogen spillover between humans and wildlife. To better understand the consequences of land‐use change on wildlife microbiotas, we analyzed long‐term dietary trends, gut microbiota composition, and innate immune function in common vampire bats (Desmodus rotundus) in two nearby sites in Belize that vary in landscape structure. We found that vampire bats living in a small forest fragment had more homogenous diets indicative of feeding on livestock and shifts in microbiota heterogeneity, but not overall composition, compared to those living in an intact forest reserve. We also found that irrespective of sampling site, vampire bats which consumed relatively more livestock showed shifts in some core bacteria compared with vampire bats which consumed relatively less livestock. The relative abundance of some core microbiota members was associated with innate immune function, suggesting that future research should consider the role of the host microbiota in immune defense and its relationship to zoonotic infection dynamics. We suggest that subsequent homogenization of diet and habitat loss through livestock rearing in the Neotropics may lead to disruption to the microbiota that could have downstream impacts on host immunity and cross‐species pathogen transmission.