常见三种类型胆结石胆汁中细菌群落的检测

目的 探讨常见三种类型胆结石胆汁中所含微生物群落的差异性.方法 采用末端限制性片断长度多态性(T-RFLP)技术对50例三种类型胆结石患者的胆汁细菌群落进行基因序列分析.结果(1)细菌16S rDNA基因片段的阳性检出率为76％(38/50),三组之间阳性检出率差异无统计学意义;(2)三组细菌16S rDNA基因片段分析,纯胆固醇组的细菌群落主要以肺炎克雷伯氏菌和金黄色葡萄球菌为主;胆色素结石组主要包括普通变形杆菌、厌氧消化球菌等;混合性结石胆汁组主要为厌氧消化球菌、丙酸杆菌,其中还包括了胆色素结石胆汁组中未检测到的黄微杆菌和希氏短杆菌.结论 胆结石患者胆汁标本中细菌检出率较高,但各组细菌群落构成各有不同,且成分较为复杂.     

Metagenomic systems biology and metabolic modeling of the human microbiome

The human microbiome is a key contributor to health and development. Yet little is known about the ecological forces that are at play in defining the composition of such host-associated communities. Metagenomics-based studies have uncovered clear patterns of community structure but are often incapable of distinguishing alternative structuring paradigms. In a recent study, we integrated metagenomic analysis with a systems biology approach, using a reverse ecology framework to model numerous human microbiota species and to infer metabolic interactions between species. Comparing predicted interactions with species composition data revealed that the assembly of the human microbiome is dominated at the community level by habitat filtering. Furthermore, we demonstrated that this habitat filtering cannot be accounted for by known host phenotypes or by the metabolic versatility of the various species. Here we provide a summary of our findings and offer a brief perspective on related studies and on future approaches utilizing this metagenomic systems biology framework.     

Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.     

Characterisation and therapeutic manipulation of the gut microbiome in inflammatory bowel disease

Inflammatory bowel diseases are thought to develop as a result of dysregulation of the relationship that exists between the gut microbiota, host genetics and the immune system. The advent of culture‐independent techniques has revolutionised the ability to characterise the role of the gut microbiota in health and disease based on the microbiota's genetic make‐up. Inflammatory bowel diseases are characterised by dysbiosis which is an imbalance between pro‐ and anti‐inflammatory bacteria and a reduction in bacterial diversity. Emerging data suggest that it is not only the presence of the gut microbiota but the functional activity of the microbiota that appears to play an important role in health and disease. Current strategies to manipulate therapeutically the gut microbiota using dietary modification, prebiotics, probiotics, antibiotics and faecal microbiota transplantation aim to restore the balance to a state of normobiosis. However, the ability of such strategies to correct dysbiosis and thereby achieve therapeutic benefit is yet to be fully characterised.     

Vasopressin deletion is associated with sex-specific shifts in the gut microbiome

Brattleboro rats harbor a spontaneous deletion of the arginine-vasopressin (Avp) gene. In addition to diabetes insipidus, these rats exhibit low levels of anxiety and depressive behaviors. Recent work on the gut-brain axis has revealed that gut microbiota can influence anxiety behaviors. Therefore, we studied the effects of Avp gene deletion on gut microbiota. Since Avp gene expression is sexually different, we also examined how Avp deletion affects sex differences in gut microbiota. Males and females show modest but differentiated shifts in taxa abundance across 3 separate Avp deletion genotypes: wildtype (WT), heterozygous (Het) and AVP-deficient Brattleboro (KO) rats. For each sex, we found examples of taxa that have been shown to modulate anxiety behavior, in a manner that correlates with anxiety behavior observed in homozygous knockout Brattleboro rats. One prominent example is Lactobacillus, which has been reported to be anxiolytic: Lactobacillus was found to increase in abundance in inverse proportion to increasing gene dosage (most abundant in KO rats). This genotype effect of Lactobacillus abundance was not found when females were analyzed independently. Therefore, Avp deletion appears to affect microbiota composition in a sexually differentiated manner.     

The role of inflammation in temporal shifts in the inflammatory bowel disease mucosal microbiome

ABSTRACT

Studies of the human intestinal microbiome in patients with inflammatory bowel disease (IBD) consistently show that there are differences (an abnormal or unbalanced microbiome, “dysbiosis”) when compared to healthy subjects. We sought to describe changes in the microbiome in individual patients over time, and determine the clinical factors that are associated with significant alteration. Forty-two mucosal biopsies were collected from 20 patients that were spaced an average of 2.4 years apart. These were analysed using bacterial 16S rRNA gene high-throughput sequencing methods. Presence of active inflammation was determined endoscopically and histologically. Inferred metagenomics analysis was conducted using the PICRUSt package. We found that the differences in the microbiome over time in individual patients were greatest in the presence of ongoing intestinal inflammation, as determined by the Yue and Clayton theta distance between sample pairs (adjusted p = 0.00031). Samples from patients with previous abdominal surgery had lower alpha (within sample) diversity compared with those with no prior operations (mean Shannon index 2.083, 2.510 respectively, p = 0.017). There were no changes in the inferred bacterial metagenomic profile. The microbiome in IBD undergoes considerable fluctuation over time. These changes are greatest when there is histologically confirmed inflammation at both time-points.     

Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health

ABSTRACT

Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (n = 1,605) and healthy controls (n = 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health.     

Restoring the gut microbiome for the treatment of inflammatory bowel diseases

Fecal microbiota transplantation(FMT)is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection(CDI)based on recent clinical trials.The pathogenesis of inflammatory bowel diseases(IBD)is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis.FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD.Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting.Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit.The long term consequences of FMT with regards to infection,cancer,auto-immune,and metabolic diseases are not known and will require continued regulation and study.Despite these limitations,FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease,particularly those with concurrent CDI or with pouchitis.     

炎症性肠病肠道淋巴细胞归巢研究进展

炎症性肠病(inflammatory bowel disease,IBD)是慢性肠道炎症疾病,传统上分为溃疡性结肠炎(ulcerative colitis,uc)和克罗恩病(Crohn's disease,CD).诸多研究表明,IBD与肠道淋巴细胞归巢(lymphocyte homing,LH)密切相关,本文就IBD与LH研究进展作一综述.     

Metagenomic systems biology and metabolic modeling of the human microbiome: From species composition to community assembly rules

The human microbiome is a key contributor to health and development. Yet little is known about the ecological forces that are at play in defining the composition of such host-associated communities. Metagenomics-based studies have uncovered clear patterns of community structure but are often incapable of distinguishing alternative structuring paradigms. In a recent study, we integrated metagenomic analysis with a systems biology approach, using a reverse ecology framework to model numerous human microbiota species and to infer metabolic interactions between species. Comparing predicted interactions with species composition data revealed that the assembly of the human microbiome is dominated at the community level by habitat filtering. Furthermore, we demonstrated that this habitat filtering cannot be accounted for by known host phenotypes or by the metabolic versatility of the various species. Here we provide a summary of our findings and offer a brief perspective on related studies and on future approaches utilizing this metagenomic systems biology framework.     

Interaction of obesity and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management.     

Giant inflammatory polyps associated with idiopathic inflammatory bowel disease

Five cases of giant inflammatory polyps associated with idiopathic inflammatory bowel disease are reported. Polyps produced intestinal obstruction in three cases; consequently, surgery was performed. In a further two cases, intestinal bleeding was improved by endoscopic polypectomy. Electron microscopy showed fibroblasts, myofibroblasts, mast cells, lymphocytes, collagen fibers, capillaries, and venules. Remnants of the original mucosal epithelial cells, smooth muscle cells, and hypertrophic autonomous nerve plexuses were noted. Nerve fibers were interwoven with the matrix of the polyps. Mast cells were closely linked with vessels, nerves, and collagen fibers. They may have an important role in the excessive granulation, angiogenesis, and fibrotic process in giant inflammatory polyps.     

Vascular complications associated with inflammatory bowel disease

Thromboembolic episode is a well known extraintestinal manifestation of inflammatory bowel disease, but it is a clinical rare complication. Histological and hematological studies suggest that a hypercoagulable state is involved in the pathogenesis of inflammatory bowel disease. However, the exact mechanism of hypercoagulability is still unknown. During the acute recurrences there is an increase of factor VIII, fibrinogen, platelet, factor V and decrease of antithrombin III. Hematologic disorders seem markedly correlated with the activity of the disease. We report on two patients with Inflammatory bowel disease and hypercoagulable state. We review the literature and discuss about the pathogenic mechanisms of such complication.     

Idiopathic pancreatitis associated with inflammatory bowel disease

The list of extraintestinal manifestations of inflammatory bowel diseases does not classically include pancreatitis and pancreatic insufficiency. We report here six cases of unexplained pancreatitis associated with inflammatory bowel disease (five patients with Crohn's disease, one with indeterminate colitis). None of the classical etiologies for pancreatitis was found in our patients; moreover none of them had duodenal localization of Crohn's disease or sclerosing cholangitis, two conditions in which pancreatitis associated with inflammatory bowel disease has been previously described. Pancreatitis was painless (or was associated with moderate and atypical abdominal pain) in four of our six cases; no pancreatic calcification was found in any case; in three patients a total or subtotal exocrine pancreatic insufficiency was evidenced. Endoscopic retrograde pancreatography performed in four subjects showed normal or minimally altered pancreatic ducts even in those with severe pancreatic insufficiency. These cases emphasize the existence of a probably nonfortuitous association of inflammatory bowel disease with pancreatitis. Its recognition could make a significant contribution in the management of inflammatory bowel disease.