肠道菌群代谢物在心血管疾病中的作用

肠道菌群在人体疾病的发生发展中具有重要作用。肠道菌群代谢宿主摄入饮食形成的代谢产物,穿透肠上皮屏障或以其他方式进入体循环,进而激活一系列信号通路影响宿主生理过程。肠道菌群代谢物多种多样,各种代谢物如何进入体循环影响心血管系统及其在心血管疾病中发挥作用的分子机制,目前已有大量研究报道。本文就几种常见肠道菌群代谢物在高血压、动脉粥样硬化及心力衰竭等心血管疾病中的作用和分子机制进行综述,为心血管疾病的治疗提供新的方向。     

Role of gut microbiota in postoperative complications and prognosis of gastrointestinal surgery: A narrative review

Gastrointestinal surgery is often challenging because of unexpected postoperative complications such as pouchitis, malabsorption, anastomotic leak, diarrhea, inflammatory responses, and life-threatening infections. Moreover, the gut microbiota has been shown to be associated with the complications described above. Major intestinal reconstruction, such as Roux-en-Y gastric bypass (RYGB) and ileal pouch-anal anastomosis surgery, could result in altered gut microbiota, which might lead to some of the benefits of these procedures but could also contribute to the development of postsurgical complications. Moreover, postsurgical reestablishment of the gut microbiota population is still poorly understood. Here, we review evidence outlining the role of gut microbiota in complications of gastrointestinal surgery, especially malabsorption, anastomotic leak, pouchitis, and infections. In addition, this review will evaluate the risks and benefits of live biotherapeutics in the complications of gastrointestinal surgery.     

基于微生物16S rDNA测序技术研究高脂血症豚鼠肠道菌群的变化

目的利用微生物16S rDNA测序技术研究高脂血症豚鼠肠道菌群的变化情况。方法豚鼠随机分为对照组和模型组,每组10只。高脂喂养8周复制高脂血症模型。第8周末测定豚鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDLC)水平;剖取肝脏、主动脉和结肠,HE染色观察肝脏、主动脉和结肠组织形态学变化; 16S rDNA测序检测豚鼠肠道内容物微生物组成和比例的变化情况。结果与对照组相比,模型组豚鼠血清TC、TG、LDLC和HDLC水平均显著升高(P0.01);组织形态学显示,模型组豚鼠均出现重度脂肪肝病变,但仅1只模型组豚鼠出现少量泡沫细胞聚集。16S rDNA基因序列分析显示,与对照组相比,在门分类学水平上,模型组豚鼠肠道互养菌门细菌比例显著增加(P0.05);在属分类学水平上,模型组豚鼠肠道毛螺旋菌NK4A136、瘤胃球菌、幽门螺杆菌、Odoribacter、Allobaculum和Caldicoprobacter细菌比例显著降低(P0.05),依赖杆菌、毛螺旋菌XPB1014、锥形杆菌和Enterorhabdus细菌比例明显升高(P0.05)。结论高脂血症豚鼠肠道菌群的组成及比例发生了明显变化。该实验结果为基于肠道菌群研究高脂血症作用机制奠定了理论基础。     

Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function

Evidence supporting the Developmental Origins of Health and Disease Hypothesis indicates that maternal nutrition in pregnancy has a significant impact on offspring disease risk later in life, likely by modulating developmental processes in utero. Gut microbiota have recently been explored as a potential mediating factor, as dietary components strongly influence microbiota abundance, function and its impact on host physiology. A growing body of evidence has additionally indicated that the intrauterine environment is not sterile as once presumed, indicating that maternal-fetal transmission of microbiota may occur during pregnancy. In this article, we will review the body of literature that supports this emerging hypothesis, as well as highlight the work in relevant animal models demonstrating associations with maternal gestational nutrition and the offspring gut microbiome that may influence offspring physiology and susceptibility to disease.     

The impact of in utero HIV exposure on gut microbiota,inflammation, and microbial translocation

ABSTRACT

HIV-exposed but uninfected (HEU) children represent a growing population and show a significantly higher number of infectious diseases, several immune alterations, compromised growth, and increased mortality rates when compared to HIV-unexposed children. Considering the impact that the gut microbiota has on general host homeostasis and immune system development and modulation, we hypothesized that HEU children present altered gut microbiota that is linked to the increased morbidity and the immune system disorders faced by them. Our experiments revealed no differences in beta and alpha diversity of the gut microbiota between HEU and unexposed children or between HIV-infected and uninfected mothers. However, there were differences in the abundance of several taxa from the gut microbiota between HEU and unexposed children and between HIV-infected and uninfected mothers. Functional prediction based on 16S rRNA sequences also indicated differences between HEU and unexposed children and between infected and uninfected mothers. In addition, we detected no differences between HEU and unexposed children in relation to weight, weight-for-age z scores, albumin serum levels, or microbial translocation and inflammation markers. In summary, HIV-infected mothers and their HIV-exposed children present alterations in the abundance of several taxa in the gut microbiome and the predicted functional metagenome when compared to uninfected mothers and unexposed children. Knowledge about the gut microbiome of HEU children in different settings is essential in order to determine better treatments for this susceptible population.     

The effect of high-fat diet on the composition of the gut microbiota in cloned and non-cloned pigs of lean and obese phenotype

The aim of this study was to investigate the effect of high-far-high-energy diet on cloned and non-cloned domestic pigs of both lean and obese phenotype and to evaluate if the lean cloned pigs had a lower inter-individual variation as compared with non-cloned pigs. The microbiota of colon and terminal ileum was investigated in cloned and non-cloned pigs that received a high-far-high-energy diet with either restricted or ad libitum access to feed, resulting in lean and obese phenotypes, respectively. The fecal microbiota of lean pigs was investigated by terminal restriction fragment length polymorphism (T-RFLP). The intestinal microbiota of lean and obese cloned and non-cloned pigs was analyzed by quantitative real time PCR and a novel high-throughput qPCR platform (Fluidigm). Principal component analysis (PCA) of the T-RFLP profiles revealed that lean cloned and non-cloned pigs had a different overall composition of their gut microbiota. The colon of lean cloned pigs contained relatively more bacteria belonging to the phylum Firmicutes and less from the phylum Bacteroidetes than obese cloned pigs as estimated by qPCR. Fluidigm qPCR results revealed differences in specific bacterial groups in the gut microbiota of both lean and obese pigs. Our results suggest that high-far-high-energy diet is associated with changes in the gut microbiota even in the absence of obesity. Overall, the cloned pigs had a different gut microbiota from that of non-cloned pigs. To our knowledge this is the first study to investigate the gut microbiota of cloned domestic pigs of lean and obese phenotype.     

Effect of acupuncture on gut microbiota in participants with subjective cognitive decline

A close relationship has recently been described between subjective cognitive decline (SCD) and gut microbiota disorders. Herein, we aim to investigate the effect of electroacupuncture (EA) on gut microbiota in participants with SCD.We conducted a study of 60 participants with SCD. Sixty participants were allocated to either EA group (n = 30) or sham acupuncture group (n = 30). Both groups received 24 sessions of real acupuncture treatment or identical treatment sessions using the placebo needle. Global cognitive change based on a comprehensive neuropsychological test battery was evaluated to detect the clinical efficacy of acupuncture treatment at the baseline and the end of treatment. Faecal microbial analyses were carried out after collecting stools at T₀ and T₁₂ weeks. Microbiomes were analyzed by 16S ribosomal RNA gene sequencing. Correlation analyses were performed to investigate the relationships between the changes in gut microbiota and symptom improvement.Age is a particularly important factor leading to the severity of dementia. Compared with sham acupuncture group, the number of Escherichia–Shigella in EA group decreased after treatment. The number of Escherichia–Shigella in EA group decreased after treatment compared with EA group before treatment. Bifidobacterium is positively correlated with clinical efficacy Z-score and Montreal Cognitive Assessment Scale (both P < .005).Acupuncture could improve global cognitive change among SCD participants by regulating the intestinal flora. Dysbiosis was found in the gut microbiome in SCD and partially relieved by acupuncture. Our study suggests that gut microbiota could be a potential therapeutic target and diagnostic biomarker for SCD.     

Marshall and Warren Lecture 2019: A paradigm shift in pathophysiological basis of irritable bowel syndrome and its implication on treatment

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder (FGID), has often been considered rather inappropriately as psychogenic in the past. Though psychological issues are important comorbidities in a proportion of IBS patients, the evidences are far from enough to label this condition as psychogenic only. In the recent past, evidences are emerging that underscores the concept supporting pure psychogenic theory of IBS and suggest this disorder to be rather microorganic. Accordingly, a move of Rome IV Committee attempting to delete the term “functional” and designating these to be disorders of “gut-brain interaction” rather than that of “brain-gut interaction,” it emphasizes the importance of the gut over the brain in the pathogenesis. The introduction of the concept of multidimensional clinical profile in Rome IV requires attention to diagnostic category of FGID, overlap, severity, psychological issues, and physiological dysfunction or biomarkers; this attempts to recognize clinical variability and multidimensionality of pathophysiology and management of these disorders. The recognition of the biological factors in the pathogenesis of IBS is a significant paradigm shift in the recent time. This is somewhat similar to the progress in the pathogenesis of peptic ulcer disease from psychological factor to acid to Helicobacter pylori infection. It is expected that in the near future, therapeutic modalities targeting the different pathogenic mechanisms of different subtypes of IBS may bring revolution in management of the disorder.     

Contribution of diet to gut microbiota and related host cardiometabolic health: diet-gut interaction in human health

ABSTRACT

Obesity and cardiometabolic diseases in both developed and developing counties in a state of nutrition transition are often related to diet, which also play a major role in shaping human gut microbiota. The human gut harbors diverse microbes that play an essential role in the well-being of their host. Complex interactions between diet and microorganisms may lead to beneficial or detrimental outcomes to host cardiometabolic health. Despite numerous studies using rodent models indicated that high-fat diet may disrupt protective functions of the intestinal barrier and contribute to inflammatory processes, evidence from population-based study is still limited. In our recent study of a 6-month randomized controlled-feeding trial, we showed that high-fat, low-carbohydrate diet was associated with unfavorable changes in gut microbiota, fecal microbial metabolites, and plasma proinflammatory factors in healthy young adults. Here, we provide an overview and extended discussion of our key findings, and outline important future directions.     

Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice

The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet. Metformin treatment decreased the expression of IL-1β and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera. In addition, both fecal microbiota transplantation from metformin-treated mice and extracellular vesicles of Akkermansia muciniphila improved the body weight and lipid profiles of the mice. Our findings suggest that modulation of the gut microbiota by metformin results in metabolic improvements in aged mice, and that these effects are associated with inflammatory immune responses.     

饮食对非酒精性脂肪性肝病肠道微生物菌型相关菌群的影响

非酒精性脂肪性肝病(NAFLD)是一种典型的慢性肝病,与肠道微生态的失调密切相关。饮食因素可能是影响肠道细菌组成和功能的最重要的驱动因素。基于肠道微生物菌型的概念,总结了饮食对NAFLD肠道微生物菌型相关菌群的影响,包含厚壁菌门/拟杆菌门的比值、拟杆菌属、普雷沃菌属、瘤胃球菌属、变形菌门、放线菌门及其他菌。指出改善饮食进而调节肠道菌群是防治NAFLD的重要策略之一,具有良好的前景,但尚需进一步的机制和临床研究。     

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.     

T lymphocytes control microbial composition by regulating the abundance of Vibrio in the zebrafish gut

Dysbiosis of the intestinal microbial community is considered a risk factor for development of chronic intestinal inflammation as well as other diseases such as diabetes, obesity and even cancer. Study of the innate and adaptive immune pathways controlling bacterial colonization has however proven difficult in rodents, considering the extensive cross-talk between bacteria and innate and adaptive immunity. Here, we used the zebrafish to study innate and adaptive immune processes controlling the microbial community. Zebrafish lack a functional adaptive immune system in the first weeks of life, enabling study of the innate immune system in the absence of adaptive immunity. We show that in wild type zebrafish, the initial lack of adaptive immunity associates with overgrowth of Vibrio species (a group encompassing fish and human pathogens), which is overcome upon adaptive immune development. In Rag1-deficient zebrafish (lacking adaptive immunity) Vibrio abundance remains high, suggesting that adaptive immune processes indeed control Vibrio species. Using cell transfer experiments, we confirm that adoptive transfer of T lymphocytes, but not B lymphocytes into Rag1-deficient recipients suppresses outgrowth of Vibrio. In addition, ex vivo exposure of intestinal T lymphocytes to Rag1-deficient microbiota results in increased interferon-gamma expression by these T lymphocytes, compared to exposure to wild type microbiota. In conclusion, we show that T lymphocytes control microbial composition by effectively suppressing the outgrowth of Vibrio species in the zebrafish intestine.     

Recent progress on the role of gut microbiota in the pathogenesis of inflammatory bowel disease

In recent years investigations of inflammatory bowel disease (IBD) have advanced rapidly with regard to the relationship between the host immune response and gut microbiota. Patients with IBD have been shown to have an abnormal composition of gut microbiota and host immune dysregulation. Abnormal components of gut microbiota, to which the host mounts aberrant immune responses in genetically vulnerable individuals, appear to play a critical role in the pathogenesis of IBD. Therefore, inappropriate innate and adaptive host immune responses to abnormal components of gut microbiota and their products form the basis of IBD pathogenesis. Modern molecular genetic methods should be utilized to help to illuminate the pathogenetic mechanism of IBD and to develop personalized therapeutic strategies for this disease.     

Sex differences and hormonal effects on gut microbiota composition in mice

We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also examined a subset of mice on chow and high fat diets and observed sex-by-diet interactions. We further investigated the sex differences using gonadectomized and hormone treated mice from 3 different inbred strains. Principal coordinate analysis with unweighted UniFrac distances revealed very clear effects of gonadectomy and hormone replacement on microbiota composition in all 3 strains. Moreover, bile acid analyses showed gender-specific differences as well as effects of gonodectomy, providing one possible mechanism mediating sex differences in microbiota composition.