Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness

Epigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic (from stool), epigenetic (from blood), and exercise-related data from physically active individuals and, by applying epigenetic clocks, we examined the relationship between gut flora, blood-based epigenetic age acceleration, and physical fitness. We revealed that an increased entropy in the gut microbiome of physically active middle-aged/old individuals is associated with accelerated epigenetic aging, decreased fitness, or impaired health status. We also observed that a slower epigenetic aging and higher fitness level can be linked to altered abundance of some bacterial species often linked to anti-inflammatory effects. Overall our data suggest that alterations in the microbiome can be associated with epigenetic age acceleration and physical fitness.     

The bacterial and fungal nest microbiomes in populations of the social spider Stegodyphus dumicola

Social spiders of the species Stegodyphus dumicola live in communal nests with hundreds of individuals and are characterized by extremely low species-wide genetic diversity. The lack of genetic diversity in combination with group living imposes a potential threat for infection by pathogens. We therefore proposed that specific microbial symbionts inhabiting the spider nests may provide antimicrobial defense. To compare the bacterial and fungal diversity in 17 nests from three different locations in Namibia, we used 16S rRNA gene and internal transcribed spacer (ITS2) sequencing. The nest microbiomes differed between geographically distinct spider populations and appeared largely determined by the local environment. Nevertheless, we identified a core microbiome consisting of four bacterial genera (Curtobacterium, Modestobacter, Sphingomonas, Massilia) and four fungal genera (Aureobasidium, Didymella, Alternaria, Ascochyta), which likely are selected from surrounding soil and plants by the nest environment. We did not find indications for a strain- or species-specific symbiosis in the nests. Isolation of bacteria and fungi from nest material retrieved a few bacterial strains with antimicrobial activity but a number of antimicrobial fungi, including members of the fungal core microbiome. The significance of antimicrobial taxa in the nest microbiome for host protection remains to be shown.     

Alterations in the gut microbiota and metabolite profiles of patients with Kashin-Beck disease,an endemic osteoarthritis in China

Kashin-Beck disease (KBD) is a severe osteochondral disorder that may be driven by the interaction between genetic and environmental factors. We aimed to improve our understanding of the gut microbiota structure in KBD patients of different grades and the relationship between the gut microbiota and serum metabolites. Fecal and serum samples collected from KBD patients and normal controls (NCs) were used to characterize the gut microbiota using 16S rDNA gene and metabolomic sequencing via liquid chromatography-mass spectrometry (LC/MS). To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria in the KBD patients, metagenomic sequencing of fecal samples from grade I KBD, grade II KBD and NC subjects was performed. The KBD group was characterized by elevated levels of Fusobacteria and Bacteroidetes. A total of 56 genera were identified to be significantly differentially abundant between the two groups. The genera Alloprevotella, Robinsoniella, Megamonas, and Escherichia_Shigella were more abundant in the KBD group. Consistent with the 16S rDNA analysis at the genus level, most of the differentially abundant species in KBD subjects belonged to the genus Prevotella according to metagenomic sequencing. Serum metabolomic analysis identified some differentially abundant metabolites among the grade I and II KBD and NC groups that were involved in lipid metabolism metabolic networks, such as that for unsaturated fatty acids and glycerophospholipids. Furthermore, we found that these differences in metabolite levels were associated with altered abundances of specific species. Our study provides a comprehensive landscape of the gut microbiota and metabolites in KBD patients and provides substantial evidence of a novel interplay between the gut microbiome and metabolome in KBD pathogenesis.Subject terms: Metagenomics, Metabolomics     

Alterations in tear biochemistry associated with postanesthetic chronic dry eye syndrome

Perioperative dry eye syndrome (DES) is a common ocular complication of long-term general anesthesia. Chronic DES can lead to permanent damage to the cornea and disturbance of visual function, up to total loss of vision. Here, a relationship between the duration of general anesthesia and the risk of chronic DES in patients was demonstrated. Using an experimental model of perioperative corneal abrasions in rabbits, it was found that introduction of animals to 3-h general anesthesia resulted in clinically significant chronic damage to the cornea in 50% of cases. The development of the complication was not associated with irreversible or long-term impairment of tear secretion, but it was accompanied by a decrease in tear film stability and growth of the total protein content as well as decrease in total antioxidant activity of the tear induced by low molecular weight antioxidants. In addition, anesthesia-induced changes in activity of tear antioxidant enzymes including superoxide dismutase and enzymes providing homeostasis of reduced glutathione (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) were observed. All these alterations were protracted (up to 1-2 weeks) and therefore might account for transition of the perioperative DES into the chronic form. These findings can be useful in the development of novel approaches for the prevention and treatment of chronic forms of DES in the postanesthetic period.     

Variations in inflammatory genes are associated with periodontitis

Background

Periodontitis is a multi-factorial disease and several risk-factors such as infections, inflammatory responses, oral hygiene, smoke, aging and individual predisposition are involved in the disease. Pathogens trigger chronic inflammation with cytokines release which in turn leads to the destruction of the connective and the teeth supporting bone. The identification of genetic factors controlling oral inflammation may increase our understanding of genetic predisposition to periodontitis.Single nucleotide polymorphisms in the promoter region of Vascular Endothelial Growth Factor, Alpha-1-Antichymotripsin, hydroxy-methyl-glutaryl CoA reductase, Interferon alpha, Interleukin-1 Beta, Interleukin 10, Interleukin 6 and Tumor Necrosis Factor- alpha genes from a case/control study were investigated.

Results

The C allele of Vascular Endothelial Growth Factor, A allele of Interleukin 10 and GG genotype of Tumor Necrosis Factor-α were individually associated with chronic periodontitis. However, the concomitant presence of the three genetic markers in the same subjects appeared to play a synergistic role and increased several folds the risk of the disease.

Conclusions

Our findings offer new tools to implement the screening of unaffected subjects with an increased susceptibility of periodontitis and increase our understanding regarding the genetic inflammatory background related to familiarity of the disease.

     

Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.Subject terms: Microbiome, Metagenomics, Next-generation sequencing, Metabolomics     

Dynamics of bacterial and fungal communities associated with eggshells during incubation

Microorganisms are closely associated with eggs and may play a determinant role in embryo survival. Yet, the majority of studies focusing on this association relied on culture‐based methodology, eventually leading to a skewed assessment of microbial communities. By targeting the 16S rRNA gene and internal transcribed spacer (ITS) region, we, respectively, described bacterial and fungal communities on eggshells of the homing pigeon Columba livia. We explored their structure, abundance, and composition. Firstly, we showed that sampling technique affected the outcome of the results. While broadly used, the egg swabbing procedure led to a lower DNA extraction efficiency and provided different profiles of bacterial communities than those based on crushed eggshell pieces. Secondly, we observed shifts in bacterial and fungal communities during incubation. At late incubation, bacterial communities showed a reduction in diversity, while their abundance increased, possibly due to the competitive advantage of some species. When compared to their bacterial counterparts, fungal communities also decreased in diversity at late incubation. In that case, however, the decline was associated with a diminution of their overall abundance. Conclusively, our results showed that although incubation might inhibit microbial growth when compared to unincubated eggs, we observed the selective growth of specific bacterial species during incubation. Moreover, we showed that fungi are a substantial component of the microbial communities associated with eggshells and require further investigations in avian ecology. Identifying the functional roles of these microorganisms is likely to provide news insights into the evolutionary strategies that control embryo survival.     

Significance of nervous system in inflammatory disease of the gut

The review is dedicated to the role of sensory nerve endings of the gut, vegetal and central nervous system (CNS) in the diseases of gastrointestinal tract. Molecular-cellular inter-relations of nerve endings of the gut and neurons of the CNS are a key axis that among with neuroendocrine and immune responses, define the clinical manifestation and rehabilitation potential of the patient in the development of infectious process in the gut. Infectious-inflammation processes in the gut of various etiologies promote the increase of permeability of the intestine barrier with consequent trans-intestinal translocation of toxins and molecular mediators of inflammation to the system bloodstream. Bacterial toxins including LPS and cytokine imbalance induce microglia damage that defines destabilization of the barrier and vulnerability of neurons. The consequence is the inadequate reaction from autonomous nervous system with the development of uncontrolled abdominal spasms and increasing muscular atrophy. Toxemia at the same time promotes the increase of hematoencephalic barrier permeability, intake of inflammatory cytokines into the brain that induce inflammation in the brain periventricular areas with the development of intestinal encephalopathy. The assumed pathogenetic mechanism dictates a new therapy strategy that is mainly directed at brain protection: administration of etiotropic and anti-inflammatory drags, myotropic spasmolytics and various neuroprotectors.     

Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes

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IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

Introduction

Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27.

Methods

IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters.

Results

Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction.

Conclusions

A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients.This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083     

Meta-analyses of human gut microbes associated with obesity and IBD

Recent studies have linked human gut microbes to obesity and inflammatory bowel disease, but consistent signals have been difficult to identify. Here we test for indicator taxa and general features of the microbiota that are generally consistent across studies of obesity and of IBD, focusing on studies involving high-throughput sequencing of the 16S rRNA gene (which we could process using a common computational pipeline). We find that IBD has a consistent signature across studies and allows high classification accuracy of IBD from non-IBD subjects, but that although subjects can be classified as lean or obese within each individual study with statistically significant accuracy, consistent with the ability of the microbiota to experimentally transfer this phenotype, signatures of obesity are not consistent between studies even when the data are analyzed with consistent methods. The results suggest that correlations between microbes and clinical conditions with different effect sizes (e.g. the large effect size of IBD versus the small effect size of obesity) may require different cohort selection and analysis strategies.     

Xanosporic acid,an intermediate in bacterial degradation of the fungal phototoxin cercosporin

The red fungal perylenequinone phototoxin cercosporin is oxidized by Xanthomonas campestris pv zinniae to a non-toxic, unstable green metabolite xanosporic acid, identified via its lactone as 1,12-bis(2'R-hydroxypropyl)-4,9-dihydroxy-6,7-methylenedioxy-11-methoxy-3-oxaperylen-10H-10-one-2-carboxylic acid. Xanosporolactone was isolated in approximately 2:1 ratio of M:P atropisomers.     

Functional profiling of the gut microbiomes in two different populations of the brown planthopper,Nilaparvata lugens

Previous studies have demonstrated that gut symbionts are involved in the detoxification metabolism of insect hosts, but the relationship between gut symbionts and host detoxification metabolism of the brown planthopper (Nilaparvata lugens, BPH) remains unclear. In the present study, an indoor population (NlIP) and a field population (NlFP) of the BPH were used to characterize the functional profiling of the gut microbiome based on 16S rDNA sequencing. The results show that the NlIP and NlFP strains of N. lugens had different symbiont compositions, and Proteobacteria, Actinobacteria, and Firmicutes were the dominate phyla, accounting for >75% of the total symbiont compositions. Additionally, the NlIP strain had more Pantoea and Stenotrophomonas, while the NlFP strain showed a higher Wolbachia, Actinobacteria, and Herbaspirillum relative abundance. Furthermore, functional content of the metagenome predicted by PICRUSt demonstrated no significant difference in metagenomic function between the NlIP and NlFP strains in the principal component analysis (PCA), and only three types of genes, namely, genes involved with metabolic diseases, poorly characterized genes, and genes involved in circulatory systems, were different between the strains based on KEGG pathway analysis, which also speculated that gut symbionts are not directly involved in the detoxification metabolism for insecticides in the BPH. These results will be helpful for further research into the mechanisms of gut symbionts involved in detoxification metabolism in the BPH.     

Anti-obesity effects of gut microbiota are associated with lactic acid bacteria

The prevalence of obesity is rapidly becoming endemic in industrialized countries and continues to increase in developing countries worldwide. Obesity predisposes people to an increased risk of developing metabolic syndrome. Recent studies have described an association between obesity and certain gut microbiota, suggesting that gut microbiota might play a critical role in the development of obesity. Although probiotics have many beneficial health effects in humans and animals, attention has only recently been drawn to manipulating the gut microbiota, such as lactic acid bacteria (LAB), to influence the development of obesity. In this review, we first describe the causes of obesity, including the genetic and environmental factors. We then describe the relationship between the gut microbiota and obesity, and the mechanisms by which the gut microbiota influence energy metabolism and inflammation in obesity. Lastly, we focus on the potential role of LAB in mediating the effects of the gut microbiota in the development of obesity.     

Alterations in gut microbiota and metabolites associated with altitude-induced cardiac hypertrophy in rats during hypobaric hypoxia challenge

The gut microbiota is involved in host responses to high altitude. However, the dynamics of intestinal microecology and their association with altitude-related illness are poorly understood. Here, we used a rat model of hypobaric hypoxia challenge to mimic plateau exposure and monitored the gut microbiome, short-chain fatty acids (SCFAs), and bile acids (BAs) over 28 d. We identified weight loss, polycythemia, and pathological cardiac hypertrophy in hypoxic rats, accompanied by a large compositional shift in the gut microbiota, which is mainly driven by the bacterial families of Prevotellaceae, Porphyromonadaceae, and Streptococcaceae. The aberrant gut microbiota was characterized by increased abundance of the Parabacteroides, Alistipes, and Lactococcus genera and a larger Bacteroides to Prevotella ratio. Trans-omics analyses showed that the gut microbiome was significantly correlated with the metabolic abnormalities of SCFAs and BAs in feces, suggesting an interaction network remodeling of the microbiome-metabolome after the hypobaric hypoxia challenge. Interestingly, the transplantation of fecal microbiota significantly increased the diversity of the gut microbiota, partially inhibited the increased abundance of the Bacteroides and Alistipes genera, restored the decrease of plasma propionate, and moderately ameliorated cardiac hypertrophy in hypoxic rats. Our results provide an insight into the longitudinal changes in intestinal microecology during the hypobaric hypoxia challenge. Abnormalities in the gut microbiota and microbial metabolites contribute to the development of high-altitude heart disease in rats.

     

An overview of major metagenomic studies on human microbiomes in health and disease

Many microbes are important symbiotes of human. They form specific microbiota communities, participate in various kinds of biological processes of their host and thus deeply affect human health status. Metagenomic sequencing has been widely used in human microbiota study due to its capacity of studying all genetic materials in an environment as a whole without any extra need of isolation or cultivation of microorganisms. Many efforts have been made by researchers in this area trying to dig out interesting knowledge from various metagenome data. In this review, we go through some prominent studies in the metagenomic area. We summarize them into three categories, constructing taxonomy and gene reference, characterization of microbiome distribution patterns, and detection of microbiome alternations associated with specific human phenotypes or diseases. Some available data resources are also provided. This review can serve as an entrance to this exciting and rapidly developing field for researchers interested in human microbiomes.     

难治性癫痫婴幼儿肠道菌群的变化

目的探讨难治性癫痫婴幼儿的肠道菌群特点。方法研究纳入年龄1~3岁的确诊难治性癫痫婴幼儿14例,同时匹配同年龄段健康婴幼儿30例作为对照。留取受试者的粪便标本,提取总DNA并扩增,对16S rRNA基因进行高通量测序,对测序结果进行生物学分析。结果两组婴幼儿样本门水平的优势菌群主要有厚壁菌、拟杆菌、变形菌和放线菌四类,癫痫组婴幼儿拟杆菌和放线菌所占比例明显低于健康组(28.60%vs 53.19%,2.58%vs 8.50%),而厚壁菌和变形菌的比例则明显高于健康组(43.19%vs 34.00%,24.87%vs 3.09%)。癫痫组婴幼儿Cronobacter属和Erysipelatoclostridium属的比例高于健康组(23.59%vs 0.86%,9.50%vs 0.76%),而拟杆菌和双歧杆菌的比例明显低于健康组(19.44%vs 42.84%,1.04%vs 7.85%)。结论婴幼儿难治性癫痫存在肠道微生态失衡,尚需进一步研究肠道菌群在难治性癫痫发病中的作用。