肺部菌群与呼吸道疾病的相互关系

由于呼吸道黏膜免疫系统具有很好的防御保护作用和强大的清除病原体的能力,过去学术界曾经一度认为健康机体的肺是无菌的。随着不依赖于体外培养的第二代测序技术的发展,关于肺部共生微生物的结构组成及其免疫调节功能的研究越来越受重视。肺部菌群的结构组成与出生方式、饮食结构、生活环境和抗生素使用等多种因素有关,生命早期的肺部菌群的形成和发育会影响全生命周期的呼吸道疾病的发生和发展。肺部菌群通过与宿主免疫系统相互作用调节肺部免疫稳态,还可以与肠道菌群、呼吸道病毒相互作用影响呼吸道感染。因此,干预生命早期肺部菌群的结构组成可以成为预防和控制呼吸道疾病的有效策略和新靶点。     

Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time

Genetics, diet, and other environmental exposures are thought to be major factors in the development and composition of the intestinal microbiota of animals. However, the relative contributions of these factors in adult animals, as well as variation with time in a variety of important settings, are still not fully understood. We studied a population of inbred, female mice fed the same diet and housed under the same conditions. We collected fecal samples from 46 individual mice over two weeks, sampling four of these mice for periods as long as 236 days for a total of 190 samples, and determined the phylogenetic composition of their microbial communities after analyzing 1,849,990 high-quality pyrosequencing reads of the 16S rRNA gene V3 region. Even under these controlled conditions, we found significant inter-individual variation in community composition, as well as variation within an individual over time, including increases in alpha diversity during the first 2 months of co-habitation. Some variation was explained by mouse membership in different cage and vendor shipment groups. The differences among individual mice from the same shipment group and cage were still significant. Overall, we found that 23% of the variation in intestinal microbiota composition was explained by changes within the fecal microbiota of a mouse over time, 12% was explained by persistent differences among individual mice, 14% by cage, and 18% by shipment group. Our findings suggest that the microbiota of controlled populations of inbred laboratory animals may not be as uniform as previously thought, that animal rearing and handling may account for some variation, and that as yet unidentified factors may explain additional components of variation in the composition of the microbiota within populations and individuals over time. These findings have implications for the design and interpretation of experiments involving laboratory animals.     

Short-Chain Fructo-Oligosaccharides Modulate Intestinal Microbiota and Metabolic Parameters of Humanized Gnotobiotic Diet Induced Obesity Mice

Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS) are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat)) or an isocaloric HF diet containing 10% of scFOS (HF-scFOS). Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids) as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full) but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia.     

Responses of gut microbiota to diet composition and weight loss in lean and obese mice

Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.     

Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity

The gut microbiota is a complex ecological community that plays multiple critical roles within a host. Known intrinsic and extrinsic factors affect gut microbiota structure, but the influence of host genetics is understudied. To investigate the role of host genetics upon the gut microbiota structure, we performed a longitudinal study in which we evaluated the hindgut microbiota and its association with animal growth and immunity across life. We evaluated three different growth stages in an Angus-Brahman multibreed population with a graduated spectrum of genetic variation, raised under variable environmental conditions and diets. We found the gut microbiota structure was changed significantly during growth when preweaning, and fattening calves experienced large variations in diet and environmental changes. However, regardless of the growth stage, we found gut microbiota is significantly influenced by breed composition throughout life. Host genetics explained the relative abundances of 52.2%, 40.0%, and 37.3% of core bacterial taxa at the genus level in preweaning, postweaning, and fattening calves, respectively. Sutterella, Oscillospira, and Roseburia were consistently associated with breed composition at these three growth stages. Especially, butyrate-producing bacteria, Roseburia and Oscillospira, were associated with nine single-nucleotide polymorphisms (SNPs) located in genes involved in the regulation of host immunity and metabolism in the hindgut. Furthermore, minor allele frequency analysis found breed-associated SNPs in the short-chain fatty acids (SCFAs) receptor genes that promote anti-inflammation and enhance intestinal epithelial barrier functions. Our findings provide evidence of dynamic and lifelong host genetic effects upon gut microbiota, regardless of growth stages. We propose that diet, environmental changes, and genetic components may explain observed variation in critical hindgut microbiota throughout life.Subject terms: Microbiome, Agricultural genetics     

Comparative analysis of microbiota along the length of the gastrointestinal tract of two tree squirrel species (Sciurus aberti and S. niger) living in sympatry

Microbiota inhabiting the gastrointestinal (GI) tract of animals has important impacts on many host physiological processes. Although host diet is a major factor influencing the composition of the gut micro‐organismal community, few comparative studies have considered how differences in diet influence community composition across the length of the GI tract. We used 16S sequencing to compare the microbiota along the length of the GI tract in Abert's (Sciurus aberti) and fox squirrels (S. niger) living in the same habitat. While fox squirrels are generalist omnivores, the diet of Abert's squirrels is unusually high in plant fiber, particularly in winter when they extensively consume fiber‐rich inner bark of ponderosa pine (Pinus ponderosa). Consistent with previous studies, microbiota of the upper GI tract of both species consisted primarily of facultative anaerobes and was less diverse than that of the lower GI tract, which included mainly obligate anaerobes. While we found relatively little differentiation between the species in the microbiota of the upper GI tract, the community composition of the lower GI tract was clearly delineated. Notably, the Abert's squirrel lower GI community was more stable in composition and enriched for microbes that play a role in the degradation of plant fiber. In contrast, overall microbial diversity was higher in fox squirrels. We hypothesize that these disparities reflect differences in diet quality and diet breadth between the species.     

Association between the ABO blood group and the human intestinal microbiota composition

ABSTRACT: BACKGROUND: The mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved. RESULTS: In this study, we show that ABO blood group is involved in differences in relative proportion and overall profiles of intestinal microbiota. Specifically, the microbiota from the individuals harbouring the B antigen (secretor B and AB) differed from the non-B antigen groups and also showed higher diversity of the Eubacterium rectale-Clostridium coccoides (EREC) and Clostridium leptum (CLEPT) -groups in comparison with other blood groups. CONCLUSIONS: Our novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine.     

Enteric pathogen exploitation of the microbiota-generated nutrient environment of the gut

Residing within the intestine is a large community of commensal organisms collectively termed the microbiota. This community generates a complex nutrient environment by breaking down indigestible food products into metabolites that are used by both the host and the microbiota. Both the invading intestinal pathogen and the microbiota compete for these metabolites, which can shape both the composition of the flora, as well as susceptibility to infection. After infection is established, pathogen mediated inflammation alters the composition of the microbiota, which further shifts the makeup of metabolites in the gastrointestinal tract. A greater understanding of the interplay between the microbiota, the metabolites they generate, and susceptibility to enteric disease will enable the discovery of novel therapies against infectious disease.     

Living the high life: Could gut microbiota matter for adaptation to high altitude?

At high altitude, the reduced availability of thermal energy and oxygen poses major challenges to organisms. Different species or populations have evolved similar solutions to these challenges, such as blood flow regulation in animals (Bouverot, 1985). Previous studies investigating such convergent adaptations have primarily looked at changes in host genomes (e.g., see Scheinfeldt & Tishkoff, 2010), but have rarely considered the potential role of the gut microbiome in mediating host adaptation. As gut microbes can indirectly regulate host blood pressure (Pluznick, 2014) and energy intake efficiency, it has been hypothesized that they could help maintain normal energy production and/or optimize nutritional assimilation in high‐altitude hypoxic environments (e.g., Li & Zhao, 2015). However, it has been hard to (a) show that there is a direct effect of altitude on the gut microbiota, because of the many potential confounding effects of altitude (e.g., diet is correlated to altitude, as well as to the microbiome) and to (b) understand the mechanisms by which the microbiota could mediate host hypoxic and thermoregulatory stresses. In this issue of Molecular Ecology, Suzuki, Martins, and Nachman (2018) show that, independently of diet, taxonomic composition and functions of mouse gut microbiota converge in independent high‐altitude environments and propose the intriguing hypothesis that some of these functional convergences might be beneficial to their host.     

The gut microbiota of brood parasite and host nestlings reared within the same environment: disentangling genetic and environmental effects

Gut microbiota are essential for host health and survival, but we are still far from understanding the processes involved in shaping their composition and evolution. Controlled experimental work under lab conditions as well as human studies pointed at environmental factors (i.e., diet) as the main determinant of the microbiota with little evidence of genetic effects, while comparative interspecific studies detected significant phylogenetic effects. Different species, however, also differ in diet, feeding behavior, and environmental characteristics of habitats, all of which also vary interspecifically, and, therefore, can potentially explain most of the detected phylogenetic patterns. Here, we take advantage of the reproductive strategy of avian brood parasites and investigate gut microbiotas (esophageal (food and saliva) and intestinal) of great spotted cuckoo (Clamator glandarius) and magpie (Pica pica) nestlings that grow in the same nests. We also estimated diet received by each nestling and explored its association with gut microbiota characteristics. Although esophageal microbiota of magpies and great spotted cuckoos raised within the same environment (nest) did not vary, the microbiota of cloacal samples showed clear interspecific differences. Moreover, diet of great spotted cuckoo and magpie nestlings explained the microbiota composition of esophageal samples, but not of cloaca samples. These results strongly suggest a genetic component determining the intestinal microbiota of host and parasitic bird species, indicating that interspecific differences in gut morphology and physiology are responsible for such interspecific differences.Subject terms: Microbial ecology, Community ecology     

Genotype Is a Stronger Determinant than Sex of the Mouse Gut Microbiota

The mammalian gut microbiota is considered to be determined mostly by diet, while the effect of genotype is still controversial. Here, we examined the effect of genotype on the gut microbiota in normal populations, exhibiting only natural polymorphisms, and evaluated this effect in comparison to the effect of sex. DNA fingerprinting approaches were used to profile the gut microbiota of eight different recombinant inbred mouse lines of the collaborative cross consortium, whose level of genetic diversity mimics that of a natural human population. Analyses based on automated ribosomal internal transcribed spacer analysis demonstrated significant higher similarity of the gut microbiota composition within mouse lines than between them or within same-gender groups. Thus, genetic background significantly impacts the microbiota composition and is a stronger determinant than gender. These findings imply that genetic polymorphisms help shape the intestinal microbiota of mammals and consequently could affect host susceptibility to diseases.     

The development of human gut microbiota fermentation capacity during the first year of life

Fermentation capacity of microbial ecosystems intrinsically depends on substrate supply and the ability of a microbial community to deliver monomers for fermentation. In established microbial ecosystems, the microbial community is adapted to efficiently degrade and ferment available biopolymers which is often concurrently reflected in the richness of the microbial community and its functional potential. During the first year of life, the human gut microbial environment is a rather dynamic system that is characterized by a change in physiological conditions (e.g. from aerobic to anaerobic conditions, physical growth of the gastrointestinal tract, development of the intestinal immune system) but also by a change in nutrient supply from a compositionally limited liquid to a diverse solid diet, which demands major compositional and functional changes of the intestinal microbiota. How these transitions link to intestinal microbial fermentation capacity has gained comparatively little interest so far. This mini-review aims to collect evidence that already after birth, there is seeding of a hidden population of various fermentation organisms which remain present at low abundance until the cessation of breastfeeding removes nutritional restrictions of a liquid milk-based diet. The introduction of solid food containing plant and animal material is accompanied by an altering microbiota. The concurrent increases in the abundance of degraders and fermenters lead to higher intestinal fermentation capacity indicated by increased faecal levels of the final fermentation metabolites propionate and butyrate. Recent reports indicate that the development of fermentation capacity is an important step during gut microbiota development, as chronic disorders such as allergy and atopic dermatitis have been linked to lower degradation and fermentation capacity indicated by reduced levels of final fermentation metabolites at 1 year of age.     

Intestinal microbiota and the immune system in metabolic diseases

The intestinal microbiota is comprised of millions of microorganisms that reside in the gastrointestinal tract and consistently interact with the host. Host factors such as diet and disease status affect the composition of the microbiota, while the microbiota itself produces metabolites that can further manipulate host physiology. Dysbiosis of the intestinal microbiota has been characterized in patients with certain metabolic diseases, some of which involve damage to the host intestinal epithelial barrier and alterations in the immune system. In this review, we will discuss the consequences of dietdependent bacterial dysbiosis in the gastrointestinal tract, and how the associated interaction with epithelial and immune cells impacts metabolic diseases.     

The microbiota influences the Drosophila melanogaster life history strategy

Organisms are locally adapted when members of a population have a fitness advantage in one location relative to conspecifics in other geographies. For example, across latitudinal gradients, some organisms may trade off between traits that maximize fitness components in one, but not both, of somatic maintenance or reproductive output. Latitudinal gradients in life history strategies are traditionally attributed to environmental selection on an animal's genotype, without any consideration of the possible impact of associated microorganisms (“microbiota”) on life history traits. Here, we show in Drosophila melanogaster, a key model for studying local adaptation and life history strategy, that excluding the microbiota from definitions of local adaptation is a major shortfall. First, we reveal that an isogenic fly line reared with different bacteria varies the investment in early reproduction versus somatic maintenance. Next, we show that in wild fruit flies, the abundance of these same bacteria was correlated with the latitude and life history strategy of the flies, suggesting geographic specificity of the microbiota composition. Variation in microbiota composition of locally adapted D. melanogaster could be attributed to both the wild environment and host genetic selection. Finally, by eliminating or manipulating the microbiota of fly lines collected across a latitudinal gradient, we reveal that host genotype contributes to latitude‐specific life history traits independent of the microbiota and that variation in the microbiota can suppress or reverse the differences between locally adapted fly lines. Together, these findings establish the microbiota composition of a model animal as an essential consideration in local adaptation.     

蜜蜂肠道菌群结构功能研究进展

在长期的共同进化中,肠道菌群与其宿主形成了紧密的联系,为宿主提供了许多有益的作用。作为一种社会性昆虫,蜜蜂的生活习性为其肠道菌群提供了良好而稳定的传播途径,因此,蜜蜂与其肠道菌群形成了一种紧密的互惠互利共生关系。近年来,随着对蜜蜂肠道菌群了解的不断加深,对蜜蜂肠道菌群功能的研究也不断深入,大量研究表明蜜蜂的肠道菌群在宿主食物的消化代谢、宿主免疫的激活和抵抗致病菌、调节宿主生理等方面都有着重要的作用,同时破坏肠道菌群的稳定对蜜蜂的健康有着明显的负面影响。本文对近年来西方蜜蜂肠道菌群功能研究进行了总结,旨在为进一步深入探索蜜蜂肠道菌群与其宿主的相互作用及在养蜂生产上应用肠道菌群防控疾病提供参考。     

Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects

The colonic microbiota mediates many cellular and molecular events in the host that are important to health. These processes can be affected in the elderly, because in some individuals, the composition and metabolic activities of the microbiota change with age. Detailed characterizations of the major groups of fecal bacteria in healthy young adults, in healthy elderly people, and in hospitalized elderly patients receiving antibiotics were made in this study, together with measurements of their metabolic activities, by analysis of fecal organic acid and ammonia concentrations. The results showed that total anaerobe numbers remained relatively constant in old people; however, individual bacterial genera changed markedly with age. Reductions in numbers of bacteroides and bifidobacteria in both elderly groups were accompanied by reduced species diversity. Bifidobacterial populations in particular showed marked variations in the dominant species, with Bifidobacterium angulatum and Bifidobacterium adolescentis being frequently isolated from the elderly and Bifidobacterium longum, Bifidobacterium catenulatum, Bifidobacterium boum, and Bifidobacterium infantis being detected only from the healthy young volunteers. Reductions in amylolytic activities of bacterial isolates in healthy elderly subjects and reduced short-chain fatty acid concentrations supported these findings, since bifidobacteria and bacteroides are important saccharolytic groups in the colon. Conversely, higher numbers of proteolytic bacteria were observed with feces samples from the antibiotic-treated elderly group, which were also associated with increased proteolytic species diversity (fusobacteria, clostridia, and propionibacteria). Other differences in the intestinal ecosystem in elderly subjects were observed, with alterations in the dominant clostridial species in combination with greater numbers of facultative anaerobes.     

Aquacultured Rainbow Trout (Oncorhynchus mykiss) Possess a Large Core Intestinal Microbiota That Is Resistant to Variation in Diet and Rearing Density

As global aquaculture fish production continues to expand, an improved understanding of how environmental factors interact in fish health and production is needed. Significant advances have been made toward economical alternatives to costly fishmeal-based diets, such as grain-based formulations, and toward defining the effect of rearing density on fish health and production. Little research, however, has examined the effects of fishmeal- and grain-based diets in combination with alterations in rearing density. Moreover, it is unknown whether interactions between rearing density and diet impact the composition of the fish intestinal microbiota, which might in turn impact fish health and production. We fed aquacultured adult rainbow trout (Oncorhynchus mykiss) fishmeal- or grain-based diets, reared them under high- or low-density conditions for 10 months in a single aquaculture facility, and evaluated individual fish growth, production, fin indices, and intestinal microbiota composition using 16S rRNA gene sequencing. We found that the intestinal microbiotas were dominated by a shared core microbiota consisting of 52 bacterial lineages observed across all individuals, diets, and rearing densities. Variations in diet and rearing density resulted in only minor changes in intestinal microbiota composition despite significant effects of these variables on fish growth, performance, fillet quality, and welfare. Significant interactions between diet and rearing density were observed only in evaluations of fin indices and the relative abundance of the bacterial genus Staphylococcus. These results demonstrate that aquacultured rainbow trout can achieve remarkable consistency in intestinal microbiota composition and suggest the possibility of developing novel aquaculture strategies without overtly altering intestinal microbiota composition.     

Patterns of seasonality and group membership characterize the gut microbiota in a longitudinal study of wild Verreaux's sifakas (Propithecus verreauxi)

The intestinal microbiota plays a major role in host development, metabolism, and health. To date, few longitudinal studies have investigated the causes and consequences of microbiota variation in wildlife, although such studies provide a comparative context for interpreting the adaptive significance of findings from studies on humans or captive animals. Here, we investigate the impact of seasonality, diet, group membership, sex, age, and reproductive state on gut microbiota composition in a wild population of group‐living, frugi‐folivorous primates, Verreaux's sifakas (Propithecus verreauxi). We repeatedly sampled 32 individually recognizable animals from eight adjacent groups over the course of two different climatic seasons. We used high‐throughput sequencing of the 16S rRNA gene to determine the microbiota composition of 187 fecal samples. We demonstrate a clear pattern of seasonal variation in the intestinal microbiota, especially affecting the Firmicutes‐Bacteroidetes ratio, which may be driven by seasonal differences in diet. The relative abundances of certain polysaccharide‐fermenting taxa, for example, Lachnospiraceae, were correlated with fruit and fiber consumption. Additionally, group membership influenced microbiota composition independent of season, but further studies are needed to determine whether this pattern is driven by group divergences in diet, social contacts, or genetic factors. In accordance with findings in other wild mammals and primates with seasonally fluctuating food availability, we demonstrate seasonal variation in the microbiota of wild Verreaux's sifakas, which may be driven by food availability. This study adds to mounting evidence that variation in the intestinal microbiota may play an important role in the ability of primates to cope with seasonal variation in food availability.     

Chemopreventive Metabolites Are Correlated with a Change in Intestinal Microbiota Measured in A-T Mice and Decreased Carcinogenesis

Intestinal microbiota play a significant role in nutrient metabolism, modulation of the immune system, obesity, and possibly in carcinogenesis, although the underlying mechanisms resulting in disease or impacts on longevity caused by different intestinal microbiota are mostly unknown. Herein we use isogenic Atm-deficient and wild type mice as models to interrogate changes in the metabolic profiles of urine and feces of these mice, which are differing in their intestinal microbiota. Using high resolution mass spectrometry approach we show that the composition of intestinal microbiota modulates specific metabolic perturbations resulting in a possible alleviation of a glycolytic phenotype. Metabolites including 3-methylbutyrolactone, kyneurenic acid and 3-methyladenine known to be onco-protective are elevated in Atm-deficient and wild type mice with restricted intestinal microbiota. Thus our approach has broad applicability to study the direct influence of gut microbiome on host metabolism and resultant phenotype. These results for the first time suggest a possible correlation of metabolic alterations and carcinogenesis, modulated by intestinal microbiota in A-T mice.