冬眠对达乌尔黄鼠盲肠菌群的影响

冬眠哺乳动物的肠道微生物会发生季节性变化,同时在冬眠期间动物处于禁食状态,对肠道微生物的多样性和组成也产生影响。本研究通过16S rRNA基因高通量测序分析达乌尔黄鼠育肥阶段 (起始育肥期、快速育肥期、育肥完成期) 和冬眠阶段 (冬眠早期、冬眠晚期、出眠期) 共6个时期盲肠菌群的多样性、组成和功能,并通过冗余分析 (RDA) 探究其生理特征与菌群组成和功能之间的关系,揭示达乌尔黄鼠盲肠菌群的季节性变化。菌群组成的分析显示达乌尔黄鼠盲肠菌群主要由厚壁菌门 (Firmicutes)、拟杆菌门 (Bacteroidetes) 和疣微菌门 (Verrucomicrobia) 组成。与其他时期相比,冬眠早期厚壁菌门的相对丰度减少,拟杆菌门和疣微菌门的相对丰度增加。在Alpha多样性中,起始育肥期、快速育肥期和冬眠早期的Chao1和ACE指数显著低于出眠期,育肥完成期的Simpson指数显著低于快速育肥期 (P < 0.05) 。通过加权和非加权的UniFrac距离矩阵的主坐标分析发现盲肠菌群均显示出了明显的季节性聚类。PICRUSt分析中,丁酸代谢等代谢通路在育肥阶段富集,冬眠阶段集中在氮代谢等相关通路中。RDA分析显示达乌尔黄鼠不同时期的生理特征与其盲肠菌群的组成和功能显著相关。本研究表明,冬眠使达乌尔黄鼠盲肠菌群的多样性和相对丰度发生改变,盲肠菌群组成和功能的变化调节了达乌尔黄鼠的生理代谢,使达乌尔黄鼠适应季节性的环境变化。     

Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse

The effects of the antibiotic vancomycin (2 x 100 mg/kg/day) on the gut microbiota of female mice (outbred NMRI strain) were studied, in order to assess the relative contribution of the gut microbiome to host metabolism. The host's metabolic phenotype was characterized using (1)H NMR spectroscopy of urine and fecal extract samples. Time-course changes in the gut microbiotal community after administration of vancomycin were monitored using 16S rRNA gene PCR and denaturing gradient gel electrophoresis (PCR-DGGE) analysis and showed a strong effect on several species, mostly within the Firmicutes. Vancomycin treatment was associated with fecal excretion of uracil, amino acids and short chain fatty acids (SCFAs), highlighting the contribution of the gut microbiota to the production and metabolism of these dietary compounds. Clear differences in gut microbial communities between control and antibiotic-treated mice were observed in the current study. Reduced urinary excretion of gut microbial co-metabolites phenylacetylglycine and hippurate was also observed. Regression of urinary hippurate and phenylacetylglycine concentrations against the fecal metabolite profile showed a strong association between these urinary metabolites and a wide range of fecal metabolites, including amino acids and SCFAs. Fecal choline was inversely correlated with urinary hippurate. Metabolic profiling, coupled with the metagenomic study of this antibiotic model, illustrates the close inter-relationship between the host and microbial "metabotypes", and will provide a basis for further experiments probing the understanding of the microbial-mammalian metabolic axis.     

Effects of long-term antibiotic treatment on mice urinary aromatic amino acid profiles

The gut microbiota–host co-metabolites are good indicators for representing the cross-talk between host and gut microbiota in a bi-direct manner. There is increasing evidence that levels of aromatic amino acids (AAAs) are associated with the alteration of intestinal microbial community though the effects of long-term microbial disturbance remain unclear. Here we monitored the gut microbiota composition and host–microbiota co-metabolites AAA profiles of mice after gentamicin and ceftriaxone treatments for nearly 4 months since their weaning to reveal the relationship between host and microbiome in long- term microbial disturbances. The study was performed employing targeted LC-MS measurement of AAA-related metabolites and 16S RNA sequence of mice cecal contents. The results showed obvious decreased gut microbial diversity and decreased Firmicutes/Bacteroidetes ratio in the cecal contents after long-term antibiotics treatment. The accumulated AAA (tyrosine, phenylalanine and tryptophan) and re-distribution of their downstreaming metabolites that produced under the existence of intestinal flora were found in mice treated with antibiotics for 4 months. Our results suggested that the long-term antibiotic treatment significantly changed the composition of the gut microbiota and destroyed the homeostasis in the intestinal metabolism. And the urinary AAA could be an indicator for exploring interactions between host and gut microbiota.     

Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes,Obesity, and Related Disorders

The past decade has been characterized by tremendous progress in the field of the gut microbiota and its impact on host metabolism. Although numerous studies show a strong relationship between the composition of gut microbiota and specific metabolic disorders associated with obesity, the key mechanisms are still being studied. The present review focuses on specific complex pathways as well as key interactions. For instance, the nervous routes are explored by examining the enteric nervous system, the vagus nerve, and the brain, as well as the endocrine routes (i.e., glucagon‐like peptide‐1, peptide YY, endocannabinoids) by which gut microbes communicate with the host. Moreover, the key metabolites involved in such specific interactions (e.g., short chain fatty acids, bile acids, neurotransmitters) as well as their targets (i.e., receptors, cell types, and organs) are briefly discussed. Finally, the review highlights the role of metabolic endotoxemia in the onset of metabolic disorders and the implications for alterations in gut microbiota‐host interactions and ultimately the onset of diseases.     

Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control

Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.     

Disparate Metabolic Responses in Mice Fed a High-Fat Diet Supplemented with Maize-Derived Non-Digestible Feruloylated Oligo- and Polysaccharides Are Linked to Changes in the Gut Microbiota

Studies have suggested links between colonic fermentation of dietary fibers and improved metabolic health. The objectives of this study were to determine if non-digestible feruloylated oligo- and polysaccharides (FOPS), a maize-derived dietary fiber, could counteract the deleterious effects of high-fat (HF) feeding in mice and explore if metabolic benefits were linked to the gut microbiota. C57BL/6J mice (n = 8/group) were fed a low-fat (LF; 10 kcal% fat), HF (62 kcal% fat), or HF diet supplemented with FOPS (5%, w/w). Pronounced differences in FOPS responsiveness were observed: four mice experienced cecal enlargement and enhanced short chain fatty acid production, indicating increased cecal fermentation (F-FOPS). Only these mice displayed improvements in glucose metabolism compared with HF-fed mice. Blooms in the gut microbial genera Blautia and Akkermansia were observed in three of the F-FOPS mice; these shifts were associated with reductions in body and adipose tissue weights compared with the HF-fed control mice. No improvements in metabolic markers or weights were detected in the four mice whose gut microbiota did not respond to FOPS. These findings demonstrate that FOPS-induced improvements in weight gain and metabolic health in mice depended on the ability of an individual’s microbiota to ferment FOPS.     

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment,febuxostat on the gut microbiota

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls. A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.     

Meta‐Omics‐ and Metabolic Modeling‐Assisted Deciphering of Human Microbiota Metabolism

The human microbiota is a complex community of commensal, symbiotic, and pathogenic microbes that play a crucial role in maintaining the homeostasis of human health. Such a homeostasis is maintained through the collective functioning of enzymatic genes responsible for the production of metabolites, enabling the interaction and signaling within microbiota as well as between microbes and the human host. Understanding microbial genes, their associated chemistries and functions would be valuable for engineering systemic metabolic pathways within the microbiota to manage human health and diseases. Given that there are many unknown gene metabolic functions and interactions, increasing efforts have been made to gain insights into the underlying functions of microbiota metabolism. This can be achieved through culture‐independent metagenomic approaches and metabolic modeling to simulate the microenvironment of human microbiota. In this article, the recent advances in metagenome mining and functional profiling for the discovery of the genetic and biochemical links in human microbiota metabolism as well as metabolic modeling for simulation and prediction of metabolic fluxes in the human microbiota are reviewed. This review provides useful insights into the understanding, reconstruction, and modulation of the human microbiota guided by the knowledge acquired from the basic understanding of the human microbiota metabolism.     

The footprints of gut microbial-mammalian co-metabolism

Gut microbiota are associated with essential various biological functions in humans through a "network" of microbial-host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum β-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole-melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies.     

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.     

Diet and phylogeny shape the gut microbiota of Antarctic seals: a comparison of wild and captive animals

The gut microbiota of mammals underpins the metabolic capacity and health of the host. Our understanding of what influences the composition of this community has been limited primarily to evidence from captive and terrestrial mammals. Therefore, the gut microbiota of southern elephant seals, Mirounga leonina, and leopard seals, Hydrurga leptonyx, inhabiting Antarctica were compared with captive leopard seals. Each seal exhibited a gut microbiota dominated by four phyla: Firmicutes (41.5 ± 4.0%), Fusobacteria (25.6 ± 3.9%), Proteobacteria (17.0 ± 3.2%) and Bacteroidetes (14.1 ± 1.7%). Species, age, sex and captivity were strong drivers of the composition of the gut microbiota, which can be attributed to differences in diet, gut length and physiology and social interactions. Differences in particular prey items consumed by seal species could contribute to the observed differences in the gut microbiota. The longer gut of the southern elephant seal provides a habitat reduced in available oxygen and more suitable to members of the phyla Bacteroidetes compared with other hosts. Among wild seals, 16 ‘core’ bacterial community members were present in the gut of at least 50% of individuals. As identified between southern elephant seal mother–pup pairs, ‘core’ members are passed on via vertical transmission from a young age and persist through to adulthood. Our study suggests that these hosts have co‐evolved with their gut microbiota and core members may provide some benefit to the host, such as developing the immune system. Further evidence of their strong evolutionary history is provided with the presence of 18 shared ‘core’ members in the gut microbiota of related seals living in the Arctic. The influence of diet and other factors, particularly in captivity, influences the composition of the community considerably. This study suggests that the gut microbiota has co‐evolved with wild mammals as is evident in the shared presence of ‘core’ members.     

Metagenomic analysis of taxonomic and functional changes in gut microbiota of patients with the alcohol dependence syndrome

The first metagenomic study of gut microbiota in patients with the alcohol dependence syndrome (ADS) has been performed in the whole-genome sequencing (“shotgun”) format. Taxonomic analysis revealed changes in the relative abundance of the predominant bacteria associated with inflammatioln (including increased levels of Ruminococcus gnavus and R. torques, and decreased levels of Faecalibacterium and Akkermansia genera). The microbiota of ADS patients was characterized by the presence of opportunistic pathogens rarely detected in metagenomes of healthy individuals from different countries. Comparative analysis of total metabolic potential revealed increased relative abundance of KEGG pathways associated with the response to oxidative stress. ADS patients also had increased levels of two specific groups of genes encoding enzymes involved in the metabolism of alcohol, as well as virulence factors. It is possible that gut microbiota of ADS patients demonstrating changes in both taxonomic and functional composition plays a role in modulating the effects of alcohol on the host body     

Physical Activity Differentially Affects the Cecal Microbiota of Ovariectomized Female Rats Selectively Bred for High and Low Aerobic Capacity

The gut microbiota is considered a relevant factor in obesity and associated metabolic diseases, for which postmenopausal women are particularly at risk. Increasing physical activity has been recognized as an efficacious approach to prevent or treat obesity, yet the impact of physical activity on the microbiota remains under-investigated. We examined the impacts of voluntary exercise on host metabolism and gut microbiota in ovariectomized (OVX) high capacity (HCR) and low capacity running (LCR) rats. HCR and LCR rats (age = 27wk) were OVX and fed a high-fat diet (45% kcal fat) ad libitum and housed in cages equipped with (exercise, EX) or without (sedentary, SED) running wheels for 11wk (n = 7-8/group). We hypothesized that increased physical activity would hinder weight gain, increase metabolic health and shift the microbiota of LCR rats, resulting in populations more similar to that of HCR rats. Animals were compared for characteristic metabolic parameters including body composition, lipid profile and energy expenditure; whereas cecal digesta were collected for DNA extraction. 16S rRNA gene-based amplicon Illumina MiSeq sequencing was performed, followed by analysis using QIIME 1.8.0 to assess cecal microbiota. Voluntary exercise decreased body and fat mass, and normalized fasting NEFA concentrations of LCR rats, despite only running one-third the distance of HCR rats. Exercise, however, increased food intake, weight gain and fat mass of HCR rats. Exercise clustered the gut microbial community of LCR rats, which separated them from the other groups. Assessments of specific taxa revealed significant (p<0.05) line by exercise interactions including shifts in the abundances of Firmicutes, Proteobacteria, and Cyanobacteria. Relative abundance of Christensenellaceae family was higher (p = 0.026) in HCR than LCR rats, and positively correlated (p<0.05) with food intake, body weight and running distance. These findings demonstrate that exercise differentially impacts host metabolism and gut microbial communities of female HCR and LCR rats without ovarian function.     

Metabolomics characterization of energy metabolism reveals glycogen accumulation in gut-microbiota-lacking mice

Microbiota in the gut are considered an important environmental factor associated with host metabolism and physiology. Although gut microbiota are known to contribute to hepatic lipogenesis and fat storage, little is known about how the condition influences the deposition of glycogen in the liver. To better understand and characterize the host energy metabolism in guts lacking microbiota, we compared the liver metabolome of specific pathogen-free and germ-free mice by gas chromatography-mass spectrometry combined with partial least-squares discriminant analysis. We identified 30 of 52 highly reproducible peaks in chromatograms of liver tissue extracts from the two groups of mice. The two groups showed significant differences in metabolic profile. Changes in liver metabolism involved metabolites such as amino acids, fatty acids, organic acids and carbohydrates. The metabolic profile of germ-free mice suggests that they synthesize glycogen and accumulate it in the liver through gluconeogenesis and glycogenesis. Our findings shed light on a new perspective of the role of gut microbiota in energy metabolism and will be useful to help study probiotics, obesity and metabolic diseases.     

Dynamics of Gut Microbiota in Autoimmune Lupus

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility- and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.     

Characteristics of gut microbiota in pigs with different breeds,growth periods and genders

Gut microbiota plays important roles in host nutrition, metabolism and immunity, and is affected by multiple factors. However, the understandings of the gut microbiota in pigs within different breeds, growth periods and genders from a large cohort remain largely undefined. In the present study, the characteristics of the gut microbiota in 120 pigs of different breeds, growth periods and genders were investigated using the Illumina MiSeq PE300 combined with QIIME2 platform. A total of 7 388 636 raw reads and 16 411 features were obtained. Additionally, the microbial diversity, compositions and phenotypes were described. 66.53% microbiota belonged to the top 10 most abundant genera (pan gut bacteria), and 28 species were commonly identified (core gut bacteria, commonality ≥ 75%) among the pigs. Besides, the correlations within pan and core gut microbiota were firstly investigated. The metagenomic function was predicted by using PICRUSt2. Furthermore, the explanatory effects of the influencing factors suggested that growth period was the greatest contributor to the gut microbiota in pigs. These results expanded our knowledge of mammalian gut microbiota within different influencing factors and microbial-related biological features in swine, which contributes to improving animal production and assisting animal model research.     

肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。