Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology

Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.     

How Microbes Shape Their Communities? A Microbial Community Model Based on Functional Genes

Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction(FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage(AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping(CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.     

肠道微生物对肥胖影响

肠道微生物是哺乳动物最密集的微生物群落,也是最多样化的微生物群落之一。随着宏基因组学的不断发展,肠道微生物成为热门的研究领域。肠道微生物具有保护和代谢等功能,在胰岛素抵抗和肥胖等疾病中发挥重要作用。本文介绍了肠道微生物及其代谢物通过调节食欲、神经递质合成分泌、炎性反应进而调节肥胖,探讨了肠道微生物的影响因素,展望了肠道微生物对治疗人类肥胖的应用前景。     

土壤动物肠道微生物多样性研究进展

随着分子生物学技术方法的快速发展,动物肠道微生物已成为医学、动物生理学与微生物生态学等研究领域热点。土壤动物种类繁多,分布广泛,其作为陆地生态系统重要组分,是驱动生态系统功能的关键因子。土壤动物体内的微生物由于与宿主长期共存,在与宿主协同进化中形成了丰富多样的群落结构,能够影响土壤动物本身的健康,进而介导土壤动物生态功能的实现。近些年,土壤动物肠道微生物工作方兴未艾,日渐得到重视。总结了四个部分内容：1)首先总结了土壤动物肠道微生物多样性领域的研究现状,该领域年发文量逐年增长,且近十年增长快速。土壤模式生物肠道微生物多样性研究较多且更为深入。土壤动物肠道微生物多样性组成与驱动机制、共存机制及群落构建的理论研究是该领域前沿;2)进而展示了土壤动物肠道微生物多样性组成和研究方法,土壤动物肠道菌群组成以变形菌门、厚壁菌门、放线菌门和拟杆菌门为主。早期工作基于传统分离培养,近年来新一代测序技术推动了该领域发展;3)接着关注了土壤动物肠道微生物的生态学功能,总体上体现在肠道微生物能帮助宿主分解食物基质、参与营养利用、影响寿命和繁殖及提高宿主免疫能力,且其能够影响土壤动物的气体排放及介导其对生态系...     

Short-Term Effect of Antibiotics on Human Gut Microbiota

From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002). At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016). Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04). The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.     

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.     

Bacteria,phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations

Disturbance of the beneficial gut microbial community is a potential collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Understanding antibiotic effects on bacterial communities at different intestinal locations is essential to realize the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (ileum) and large intestine (cecum and colon) plus feces, and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine and penicillin (ASP250)) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded numerous genes to degrade plant cell wall components, and these genes were lacking in the ileum. The mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar membership to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The collateral effects on the microbiota of antibiotic-fed animals caused divergence from that of control animals, with notable changes being increases in Escherichia coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. Characterizing the differential metabolic capacities and response to perturbation at distinct intestinal locations will inform strategies to improve gut health and food safety.     

Decipher enzymes from human microbiota for drug discovery and development

The human microbiota plays an important role in human health and contributes to the metabolism of therapeutic drugs affecting their potency. However, the current knowledge on human gut bacterial metabolism is limited and lacks an understanding of the underlying mechanisms of observed drug biotransformations. Despite the complexity of the gut microbial community, genomic and metagenomic sequencing provides insights into the diversity of chemical reactions that can be carried out by the microbiota and poses new challenges to functionally annotate thousands of bacterial enzymes. Here, we outline methods to systematically address the structural and functional space of the human microbiome, highlighting a combination of in silico and in vitro approaches. Systematic knowledge about microbial enzymes could eventually be applied for personalized therapy, the development of prodrugs and modulators of unwanted bacterial activity, and the further discovery of new antibiotics.     

鸡肠道微生物菌群的建立发育、分布和生理学意义

鸡的胃肠道具有复杂的微生物菌群,该微生物菌群与宿主的肠道和整体健康密切相关,为了全面揭示鸡肠道微生物菌群的组成及其功能,本文对鸡肠道微生物菌群的建立发育、各肠段群落的分布及其生理学意义进行综述,从而为鸡肠道功能菌株的分离及有效利用,合理调控微生物菌群-宿主相互作用,提高饲料转化率和改善肠道健康提供理论依据。     

人类肠道微生物组与相关疾病研究进展

人体肠道共生着数以万亿计的微生物,肠道微生物在维持宿主正常生理功能中发挥重要作用,其成分和功能变化可导致严重的肠道和全身性疾病。以新一代测序技术和生物信息学分析为基础的元基因组学研究不仅极大地推动了对人类肠道微生物的整体认识,还加深了对肠道微生物代谢产物促进人类健康机理的理解,为肠道炎症、代谢性疾病和癌症等人类疾病的诊断与治疗提供了新思路。就肠道微生物元基因组学与肠道相关疾病的研究进展作一综述。     

Exploring the gut microbiota composition of Indian major carp,rohu (Labeo rohita), under diverse culture conditions

Gut microbiota of freshwater carps are often investigated for their roles in nutrient absorption, enzyme activities and probiotic properties. However, little is known about core microbiota, assembly pattern and the environmental influence on the gut microbiota of the Indian major carp, rohu. The gut microbial composition of rohu reared in different culture conditions was analysed by 16S rRNA amplicon sequencing. There was variation on gut microbial diversity and composition. A significant negative correlation between dissolved oxygen content (DO) and alpha diversity was observed, thus signifying DO content as one of the key environmental factors that regulated the diversity of rohu gut microbial community. A significant positive correlation was observed between phosphate concentration and abundance of Actinobacteria in different culture conditions. Two phyla, Proteobacteria and Actinobacteria along with OTU750868 (Streptomyces) showed significant (p < 0.05) differences in their abundance among all culture conditions. The Non-metric multidimensional scaling ordination (NMDS) analysis using Bray-Curtis distances, showed the presence of unique gut microbiota in rohu compared to other herbivorous fish. Based on niche breadth, 3 OTUs were identified as core generalists, persistent across all the culture conditions whereas the specialists dominated in the rohu gut microbiota assembly. Co-occurrence network analysis revealed positive interaction within core members while mutual exclusion between core and non-core members. Predicted microbiota function revealed that different culture conditions affected the metabolic capacity of gut microbiota of rohu. The results overall indicated the significant effect of different rearing environments on gut microbiota structure, assembly and inferred community function of rohu which might be useful for effective manipulation of gut microbial communities of rohu to promote better health and growth under different husbandry settings.     

Convergent dynamics of the juvenile European sea bass gut microbiota induced by poly-β-hydroxybutyrate

Poly-β-hydroxybutyrate (PHB) is a bacterial energy and carbon storage compound which exhibits a controlling effect on the gastrointestinal microbiota. Its beneficial activities for aquaculture have already been shown in terms of increased disease resistance and growth performance in a number of studies. However, the action of PHB on the intestinal microbial community in the treated animals has not yet been studied in depth. In this research, the effects of PHB on the microbiota composition in the intestinal tract of juvenile sea bass were examined. It was found that fish cohabiting in the same tank were on average 87% similar regarding the intestinal microbiota. When subjected to the same treatment and environmental conditions but reared in different tanks, the compositions of the enteric communities diverged. The provision of PHB overruled this tank effect by sustaining a microbial core community in the gut that represented 60% of the total bacterial diversity at the highest PHB level of 10%. The microbial community compositions converged between replicate tanks upon supplementation of PHB and were characterized by high dynamics and increased evenness. The results are discussed in the framework of hypotheses that try to relate the intestinal microbial community composition to the health status of the host organisms.     

Intestinal microbiota in fishes: what's known and what's not

High‐throughput sequencing approaches have enabled characterizations of the community composition of numerous gut microbial communities, which in turn has enhanced interest in their diversity and functional relationships in different groups of vertebrates. Although fishes represent the greatest taxonomic and ecological diversity of vertebrates, our understanding of their gut microbiota and its functional significance has lagged well behind that of terrestrial vertebrates. In order to highlight emerging issues, we provide an overview of research on fish gut microbiotas and the biology of their hosts. We conclude that microbial community composition must be viewed within an informed context of host ecology and physiology, and that this is of particular importance with respect to research planning and sampling design.     

Catching a glimpse of the bacterial gut community of companion animals: a canine and feline perspective

Dogs and cats have gained a special position in human society by becoming our principal companion animals. In this context, efforts to ensure their health and welfare have increased exponentially, with in recent times a growing interest in assessing the impact of the gut microbiota on canine and feline health. Recent technological advances have generated new tools to not only examine the intestinal microbial composition of dogs and cats, but also to scrutinize the genetic repertoire and associated metabolic functions of this microbial community. The application of high-throughput sequencing techniques to canine and feline faecal samples revealed similarities in their bacterial composition, with Fusobacteria, Firmicutes and Bacteroidetes as the most prevalent and abundant phyla, followed by Proteobacteria and Actinobacteria. Although key bacterial members were consistently present in their gut microbiota, the taxonomic composition and the metabolic repertoire of the intestinal microbial population may be influenced by several factors, including diet, age and anthropogenic aspects, as well as intestinal dysbiosis. The current review aims to provide a comprehensive overview of the multitude of factors which play a role in the modulation of the canine and feline gut microbiota and that of their human owners with whom they share the same environment.     

肠道微生物与昆虫的共生关系

昆虫肠道栖息着大量的微生物。随着近年来研究肠道微生物的方法不断进步,尤其是基于16S rDNA的分子生物学方法的应用,人们对肠道微生物的了解逐渐加深。昆虫肠道对于微生物的拓殖存在一定的选择作用。肠道微生物对昆虫寄主的作用包括提供营养、利用拓殖抗性抵抗外来微生物侵袭、参与多重营养关系、引起昆虫免疫反应。长期进化过程中肠道微生物与昆虫发展出紧密的共生关系,微生物发展出一系列手段适应昆虫肠道环境。文章从以上几个方面对近年来的研究进展进行总结,并对昆虫肠道微生态学的实践意义和将来可能的研究热点进行展望。     

Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes.

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes.     

Exploring the bovine rumen bacterial community from birth to adulthood

The mammalian gut microbiota is essential in shaping many of its host''s functional attributes. One such microbiota resides in the bovine digestive tract in a compartment termed as the rumen. The rumen microbiota is necessary for the proper physiological development of the rumen and for the animal''s ability to digest and convert plant mass into food products, making it highly significant to humans. The establishment of this microbial population and the changes occurring with the host''s age are important for understanding this key microbial community. Despite its importance, little information about colonization of the microbial populations in newborn animals, and the gradual changes occurring thereafter, exists. Here, we characterized the overall bovine ruminal bacterial populations of five age groups, from 1-day-old calves to 2-year-old cows. We describe the changes occurring in the rumen ecosystem after birth, reflected by a decline in aerobic and facultative anaerobic taxa and an increase in anaerobic ones. Some rumen bacteria that are essential for mature rumen function could be detected as early as 1 day after birth, long before the rumen is active or even before ingestion of plant material occurs. The diversity and within-group similarity increased with age, suggesting a more diverse but homogeneous and specific mature community, compared with the more heterogeneous and less diverse primary community. In addition, a convergence toward a mature bacterial arrangement with age was observed. These findings have also been reported for human gut microbiota, suggesting that similar forces drive the establishment of gut microbiotas in these two distinct mammalian digestive systems.     

Understanding the effects of diet on bacterial metabolism in the large intestine

Recent analyses of ribosomal RNA sequence diversity have demonstrated the extent of bacterial diversity in the human colon, and have provided new tools for monitoring changes in the composition of the gut microbial community. There is now an excellent opportunity to correlate ecological niches and metabolic activities with particular phylogenetic groups among the microbiota of the human gut. Bacteria that associate closely with particulate material and surfaces in the gut include specialized primary degraders of insoluble substrates, including resistant starch, plant structural polysaccharides and mucin. Butyrate-producing bacteria found in human faeces belong mainly to the clostridial clusters IV and XIVa. In vitro and in vivo evidence indicates that a group related to Roseburia and Eubacterium rectale plays a major role in mediating the butyrogenic effect of fermentable dietary carbohydrates. Additional cluster XIVa species can convert lactate to butyrate, while some members of the clostridial cluster IX convert lactate to propionate. The metabolic outputs of the gut microbial community depend not only on available substrate, but also on the gut environment, with pH playing a major role. Better understanding of the colonic microbial ecosystem will help to explain and predict the effects of dietary additives, including nondigestible carbohydrates, probiotics and prebiotics.     

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community–host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to ‘fingerprint'' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography–mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota''s metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest ‘personalized'' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.     

Beneficial modulation of the gut microbiota

The human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.