代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析

目的 探讨在不同高脂饮食喂养时期代谢相关性脂肪性肝病(MAFLD)小鼠血糖水平和肠道菌群的动态变化.方法 采用高脂食物饲喂12只C57BL/6小鼠24周,分别在喂养0周、8周、16周和24周行葡萄糖耐量试验(GTT)和胰岛素耐受试验(ITT).采集小鼠粪便进行16sRNA检测,分析肠道细菌结构和肠道菌群多样性的变化.结...     

A new era in gut research concerning interactions between microbiota and human health

The scope of this introduction is to make a small review of the texts presented here and to emphasize some points that are not developed but that concern human microbiota functions.     

糖基化黄酮类化合物与肠道菌群的相互作用影响机体健康的研究进展

［摘要］　黄酮类化合物广泛存在于中草药、水果和蔬菜等植物中,具有多种生物效应,在诸如肥胖、糖尿病、癌症等多种代谢性疾病的改善和防治中起着很重要的作用。由于黄酮糖苷类天然产物是植物中黄酮类化合物的主要存在形式,常见的糖基配体有葡萄糖基、鼠李糖基、新橙皮糖基和芸香糖基,因此,糖基数目及其链接的位置决定了其在体内的吸收、分布、代谢和生物活性。与此同时,黄酮类化合物进入体内之后,与肠道微生物相互作用直接影响它们的代谢和生物活性。该文重点综述糖基化黄酮类化合物的体内吸收、与肠道菌群互相作用、生物活性及其在临床疾病中的应用。     

Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota

BACKGROUND Obesity is a major risk factor for a variety of diseases such as diabetes,nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction(CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction(LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.AIM To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.METHODS We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57 BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet(ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57 BL/6 mice received fecal microbiota transplantation(FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet(HFD) ad libitum for 16 wk.Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.RESULTS We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND(28.71 ± 0.29 vs 28.05 ± 0.15, P 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFDfed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight(44.95 ± 1.02 vs 40.53 ± 0.97, P 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.CONCLUSION Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.     

Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health

The complex gut microbial flora harbored by individuals （microbiota） has long been proposed to contribute to intestinal health as well as disease. Preand probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap ＇Human Microbiome Project＇ and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade（s）.     

Comparison of methodological approaches to human gut microbiota changes in response to metabolic and bariatric surgery: A systematic review

Substantial differences in the response of gut microbial composition to metabolic and bariatric surgery have been reported. Therefore, the goal of the present review is to evaluate if methodological differences could be driving this lack of consistency. A search was conducted using PUBMED, Web of Science, Science Direct and COCHRANE using the following inclusion criteria: human studies written in English with a baseline sampling point, using gut microbiota as an outcome and either Roux‐n‐Y gastric bypass or sleeve gastrectomy. Sixteen articles were selected (total 221 participants). Roux‐n‐Y gastric bypass caused more alterations in gut microbial composition in comparison with sleeve gastrectomy. Substantial variability was found in study designs, data collection and analyses across studies. Increases in several families and genera from the phylum Proteobacteria and Bacteroidetes, the family Streptococcaceae, the species Akkermansia muciniphila and Streptococcus salivarius and a decrease in the phylum Firmicutes and the family Bifidobacteriaceae were reported. There is a need for standardization not only of microbial analysis but also of study designs when analysing the effect of bariatric surgery on the human gut microbiome. In addition, outcomes from different surgical procedures should not be combined as they produce distinctive effects on gut microbial composition.     

CONSORT-Characteristics and metabolic phenotype of gut microbiota in NAFLD patients

Patients with nonalcoholic fatty liver disease (NAFLD) have symptoms of a gut microbiota disorder with abnormal amino acid and glycolipid metabolism. This study was designed to analyze the characteristics of gut microbiota in patients with NAFLD, predict the gut microbiota phenotype, explore its role in the diagnosis of NAFLD, and establish its significance in disease progression.The characteristics of the gut microbiota in NAFLD patients (n = 28, 45.8 ± 14.2 years, male/female = 18/10) and healthy subjects (n = 20, 49.6 ± 4.8 years, male/female = 14/6) during March–May 2020 were analyzed using 16S rRNA sequencing technology and the phenotypes with large differences were predicted using the Tax4Fun method. The metabolites in the fecal samples of the patients were analyzed using mass spectrometry, and their correlation with different microorganisms was examined. The accuracy of the gut microbiota in diagnosing NAFLD was investigated by receiver operating characteristic curve analysis.We found that the microbial diversity and Bacteroides/Firmicutes (BF) ratio changed significantly (P < .05) in the feces of NAFLD patients. Phenotypic prediction showed that there were significant differences in the phenotypes of amino acid, glucose, and lipid metabolism of gut microbiota in the NAFLD group (P < .05). receiver operating characteristic curve analysis revealed that combination of Bacteroides and the BF ratio resulted in 88% and 100% sensitivity and specificity, respectively, when used for NAFLD diagnosis. Metabolomics and bioinformatics analysis revealed changes in the metabolism of nicotinate, nicotinamide, and pyrimidine; signaling pathways of calcium and oxytocin; pancreatic secretion with metabolites such as uracil, xanthine, and biliverdin; and enzymes such as xanthine dehydrogenase and xanthine oxidase (P < .05).Therefore, the phenotypic changes may be a potential marker for NAFLD and we considered that a combined analysis of Bacteroides and BF ratio had good diagnostic accuracy for NAFLD.     

肠道菌群与脓毒症相互关系的研究进展

脓毒症的发生发展与肠道菌群失调密切相关.肠道菌群失调可以通过肠黏膜屏障功能破坏、黏膜免疫功能破坏和细菌移位等环节诱导脓毒症的发生.同时脓毒症也可以加重肠道菌群失调,加重肠黏膜屏障功能破坏,导致机体多器官功能障碍.本文通过探讨肠道菌群和脓毒症之间的相互关系,为脓毒症临床干预提供思路.     

肠道菌群与动脉粥样硬化的关系

动脉粥样硬化(As)是心血管疾病(CVD)的主要病理基础且其发病机制具有多样性。肠道菌群失调可通过代谢和免疫系统导致代谢失调和炎症反应,导致斑块形成和破裂,细菌感染在As形成和斑块的发展也具有一定的影响。同时肠道菌群失调可改变胆固醇代谢和菌群代谢物如氧化三甲胺(TMAO)、胆汁酸(BAs)和短链脂肪酸(SCFAs)水平影响As发病进程。目前以肠道菌群为靶点治疗As的研究逐渐深入,益生菌、益生元、粪菌移植、中药可能是未来As治疗的潜在方法并使CVD患者获益。     

Reciprocal interactions between bile acids and gut microbiota in human liver diseases

The gut microbiota (GM) play a central role in their host's metabolism of bile acids (BAs) by regulating deconjugation, dehydroxylation, dehydrogenation, and epimerization reactions to generate unconjugated free BAs and secondary BAs. These BAs generated by the GM are potent signaling molecules that interact with BA receptors, such as the farnesoid X receptor and Takeda G‐protein‐coupled receptor 5. Each BA has a differential affinity to these receptors; therefore, alterations in BA composition by GM could modify the intensity of receptor signaling. Bile acids also act as antimicrobial agents by damaging bacterial membranes and as detergents by altering intracellular macromolecular structures. Therefore, BAs and the GM reciprocally control each other's compositions. In this review, we discuss the latest findings on the mutual effects of BAs and GM on each other; we also describe their roles in the pathophysiology of liver disease progression and potential therapeutic applications of targeting this cross‐talk.     

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.     

Improving healthspan via changes in gut microbiota and fermentation

Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism.     

人体寄生虫与肠道菌群相互作用的研究进展

人体寄生虫与人和哺乳动物肠道内的共生菌会发生一些重要的相互作用。肠道内寄生虫与肠道菌群的相互作用及产生的潜在影响已有较多报道,然而有些通常并不寄生在肠道内的寄生虫也会对肠道菌群产生影响。本文就人体肠道内和肠道外寄生虫对肠道菌群影响的研究进展作一综述。     

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.     

Dynamic alterations in the gut microbiota and metabolomeduring the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis

AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P 0.001 and P 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P 0.05,and P 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.