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。     

Intestinal Microbiota in Early Life and Its Implications on Childhood Health

Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods.Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal axis.This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.     

Early life feeding accelerates gut microbiome maturation and suppresses acute post-weaning stress in piglets

Early life microbiome perturbations can have important effects on host development, physiology and behaviour. In this longitudinal study, we evaluated the impact of early feeding on gut microbiome colonization in neonatal piglets. Early-fed (EF) piglets had access to a customized fibrous diet from 2 days after birth until weaning in addition to mother's milk, whereas control piglets suckled mother's milk only. Rectal swabs were collected at multiple time points until 6 weeks of age to investigate microbiota development using 16S rRNA gene profiling. The dynamic pre-weaning microbiota colonization was followed by a relatively stable post-weaning microbiota, represented by Prevotella, Roseburia, Faecalibacterium, Ruminococcus, Megasphaera, Catenibacterium and Subdoligranulum. EF piglets showed an accelerated microbiota maturation, characterized by increased microbial diversity, pre-weaning emergence of post-weaning-associated microbes and a more rapid decline of typical pre-weaning microbes. Furthermore, the individual eating behaviour scores of piglets quantitatively correlated with their accelerated microbiome. Importantly, EF piglets displayed a smoother relative weight gain and tended to reach a higher relative weight gain, in addition to reduced diarrhoea scores in the first week post-weaning. Overall, these findings demonstrate the beneficial impact of early feeding on microbiota development as well as pig health and performance during the weaning transition.     

The potential for probiotic manipulation of the gastrointestinal microbiome

Multiple internal and external sites of the healthy human body are colonized by a diversity of symbiotic microbes. The microbial assemblages found in the intestine represent some of the most dense and diverse of these human-associated ecosystems. Unsurprisingly, the enteric microbiome, that is the totality of microbes, their combined genomes, and their interactions with the human body, has a profound impact on physiological aspects of mammalian function, not least, host immune response. Lack of early-life exposure to certain microbes, or shifts in the composition of the gastrointestinal microbiome have been linked to the development and progression of several intestinal and extra-intestinal diseases, including childhood asthma development and inflammatory bowel disease. Modulating microbial exposure through probiotic supplementation represents a long-held strategy towards ameliorating disease via intestinal microbial community restructuring. This field has experienced somewhat of a resurgence over the past few years, primarily due to the exponential increase in human microbiome studies and a growing appreciation of our dependence on resident microbiota to modulate human health. This review aims to review recent regulatory aspects related to probiotics in food. It also summarizes what is known to date with respect to human gastrointestinal microbiota - the niche which has been most extensively studied in the human system - and the evidence for probiotic supplementation as a viable therapeutic strategy for modulating this consortium.     

Gut microbiome in gastrointestinal cancer: a friend or foe?

The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.     

Gut microbiome and the risk factors in central nervous system autoimmunity

Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process.     

On the origin of species: Factors shaping the establishment of infant's gut microbiota

The human gut microbiota is a complex and dynamic ecosystem, which naturally lives in a symbiotic relationship with the host. Perturbations of the microbial composition (dysbiosis) and reduced diversity may promote disease susceptibility and recurrence. In contrast to the mature intestinal microbiota of healthy adults, which appears relatively stable over time, the infant's microbiome only establishes and matures during the first years of life. In this respect, early childhood seems to represent a crucial age‐window in disease prevention, since microbial diversification and maturation of the microbiome primarily occurs during this period of life. A better understanding of ecological processes and pioneer consortia in microbial development is crucial, in order to support the development of a beneficial microbiota. Various deterministic and stochastic aspects seem to shape the microbiome in early life, including maternal, environmental, and host factors. Here, we review the current understanding of the origin of pioneer bacteria and the evolutionary factors that influence the development of the gut microbiota in infants. In addition, future perspectives, including manipulating and promoting the succession of initial bacteria during infancy, will be highlighted. Birth Defects Research (Part C) 105:240–251, 2015. © 2015 Wiley Periodicals, Inc.     

Roles of Probiotic Lactobacilli Inclusion in Helping Piglets Establish Healthy Intestinal Inter-environment for Pathogen Defense

The gastrointestinal tract of pigs is densely populated with microorganisms that closely interact with the host and with ingested feed. Gut microbiota benefits the host by providing nutrients from dietary substrates and modulating the development and function of the digestive and immune systems. An optimized gastrointestinal microbiome is crucial for pigs’ health, and establishment of the microbiome in piglets is especially important for growth and disease resistance. However, the microbiome in the gastrointestinal tract of piglets is immature and easily influenced by the environment. Supplementing the microbiome of piglets with probiotic bacteria such as Lactobacillus could help create an optimized microbiome by improving the abundance and number of lactobacilli and other indigenous probiotic bacteria. Dominant indigenous probiotic bacteria could improve piglets’ growth and immunity through certain cascade signal transduction pathways. The piglet body provides a permissive habitat and nutrients for bacterial colonization and growth. In return, probiotic bacteria produce prebiotics such as short-chain fatty acids and bacteriocins that benefit piglets by enhancing their growth and reducing their risk of enteric infection by pathogens. A comprehensive understanding of the interactions between piglets and members of their gut microbiota will help develop new dietary interventions that can enhance piglets’ growth, protect piglets from enteric diseases caused by pathogenic bacteria, and maximize host feed utilization.     

The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation

Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli. In addition, the physiological stress response also changes many aspects of gastrointestinal physiology that can impact microbial community composition. Thus, there are many routes through which microbial community composition might be disrupted during stressful periods. The implications of these disruptions in commensal microbial communities for host health are still not well understood, but the commensal microbiota have been linked to stressor-induced immunopotentiation. The role of the microbiota in stressor-induced immunopotentiation can be adaptive, such as when these microbes stimulate innate defenses against bacterial infection. However, the commensal microbiota can also lead to maladaptive immune responses during stressor-exposure. This is evident in animal models of colonic inflammation where stressor exposure increases the inflammation through mechanisms involving the microbiota. It is likely that during stressor exposure, immune cell functioning is regulated by combined effects of both neurotransmitters/hormones and commensal microbes. Defining this regulation should be a focus of future studies.     

Nutritional influences on the gut microbiota and the consequences for gastrointestinal health

The human colonic microbiota degrades dietary substrates that are indigestible in the upper GIT (gastrointestinal tract), releasing bacterial metabolites, some of which are important for gut health. Advances in molecular biology techniques have facilitated detailed analyses of the composition of the bacterial community resident in the lower GIT. Such analyses have indicated that more than 500 different bacterial species colonize an individual, and that, although there is much functional consistency in the resident bacterial groups, there is considerable inter-individual variation at the species/strain level. The bacterial community develops during early childhood until it reaches an adult-like composition. Whereas colonization and host factors influence the species composition, dietary factors also have an important impact, with specific bacterial groups changing in response to specific dietary interventions. Since bacterial species have different metabolic activities, specific diets have various consequences for health, dependent on the effect exerted on the bacterial population.     

Taxonomic Identification of Commensal Bacteria Associated with the Mucosa and Digesta throughout the Gastrointestinal Tracts of Preweaned Calves

Bacterial colonization in the gastrointestinal tracts (GIT) of preweaned calves is very important, since it can influence early development and postweaning performance and health. This study investigated the composition of the bacteria along the GIT (rumen, jejunum, ileum, cecum, and colon) of preweaned bull calves (3 weeks old) using pyrosequencing to understand the segregation of bacteria between the mucosal surface and digesta. Phylogenetic analysis revealed that a total of 83 genera belonging to 13 phyla were distributed throughout the GIT of preweaned calves, with the Firmicutes, Bacteroidetes, and Proteobacteria predominating. Quantitative PCR (qPCR) analysis of selected abundant bacterial genera (Prevotella, Bacteroides, Lactobacillus, and Faecalibacterium) revealed that their prevalence was significantly different among the GIT regions and between mucosa- and digesta-associated communities. Rumens contained the most diverse bacterial population, consisting of 47 genera, including 16 rumen-specific genera, followed by the large intestine and then the small intestine. Bacterial species richness was higher at the mucosal surface than in the local digesta, with the exception of the rumen. The majority of bacteria found on the rumen epithelial surface and within the small intestine could not be identified due to a lack of known genus-level information. Thus, future studies will be required to fully characterize the microbiome during the development of the rumens and the mucosal immune systems of newborn calves. This is the first study to analyze in depth the bacterial composition of the GIT microbiome in preweaned calves, which extends previous findings regarding early rumen colonization and bacterial segregation between mucosa- and digesta-associated microbial communities.     

Do Maternal Microbes Shape Newborn Oral Microbes?

Strong evidence suggests that the early composition of the oral microbiota of neonates plays an important role for the postnatal development of the oral health or immune system. However, the relationship between the maternal microbiome and the initial neonatal microbiome remains unclear. In this study, 25 pregnant women and their neonates were recruited, and the samples were collected from the maternal oral cavity, amniotic fluid, placenta and neonatal oral cavity. High-throughput sequencing of 16S rRNA was performed using the Illumina MiSeq platform to analyze the correlation with microbial community structure between the maternal and the neonatal oral cavity. The results indicated that the number of shared OTUs was up to 635 in four groups. The PCoA showed that there were certain similarities in the microbial community structure of the four groups. The dominant bacterial genera of the shared OTUs were consistent with human oral microbes, including Streptococcus, Fusobacterium and Prevotella. The results showed that there might be a correlation between the maternal and neonatal oral microbiome, through the amniotic fluid and placenta.Electronic supplementary materialThe online version of this article (10.1007/s12088-020-00901-7) contains supplementary material, which is available to authorized users.     

Influence of the gastrointestinal microbiota on development of the immune system in young animals

The gastrointestinal tract (GIT) of adult mammals is colonized by a complex and dynamic community of microorganisms. Most protection against potential pathogens occurs via a mucosal immune system involving mechanisms of innate immunity as well as a secondary lymphoid organ, the gut-associated lymphoid tissue (GALT). However, the bacterial community also supports its host against invasion by potential pathogens, by a mechanism called 'colonization resistance'. Young animals need time to develop both a complex bacterial community and their immature GIT immune system, and until such developments have taken place, they are vulnerable to the presence of potential pathogens in their GIT. Initial protection against invading pathogens is provided by milk and colostrum, which contain antibodies and other bioactive components. At weaning, with the introduction of solid food and deprivation of the mother's milk, the young must also cope with a rapidly changing microbiota. The colonizing microbiota not only provides colonization resistance to potentially pathogenic bacteria. It also has a major role in the development of the intestinal immune system, both in terms of GALT development and mucosal immunity, and the induction of oral tolerance. Studies using gnotobiotic animal models have revealed that the presence of even limited numbers of the indigenous microbiota may influence the GIT immune system. Regulation of the composition of the GIT microbiota, e.g. by the use of pre- and probiotics, offers the possibility to influence the development of mucosal, and also systemic immunity.     

Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Background

Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity.

Methodology/Principal Findings

Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolator-reared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals.

Conclusions/Significance

Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.     

Microbial programming of health and disease starts during fetal life

The pioneer microbiota of the neonatal gut are essential for gut maturation, and metabolic and immunologic programming. Recent research has shown that early bacterial colonization may impact the occurrence of disease later in life (microbial programming). Despite early conflicting evidence, it has long been considered that the womb is a sterile environment and human microbial colonization begins at birth. In the last few years, several findings have reiterated the presence of microbes in infant first stool (meconium) and pointed to the existence of in utero microbial colonization of the infant gut. The dominant bacterial taxa detected in meconium specimens belong to the Enterobacteriaceae family (Escherichia genus) and lactic acid bacteria (notably members of the genera Leuconostoc, Enterococcus, and Lactococcus). Maternal atopy promotes dominance of Enterobacteriaceae in newborn meconium, which in turn may lead to respiratory problems in the infant. This microbial interaction with the host immune system may in fact, originate during fetal life. Our review evaluates the evidence for an intrauterine origin of meconium microbiota, their composition and influences, and potential clinical implications on infant health. Birth Defects Research (Part C) 105:265–277, 2015. © 2015 Wiley Periodicals, Inc.     

2016年动物胃肠道微生物组研究十大亮点成果

动物胃肠道微生物对生产性能提高具有重要的作用,因此营养、微生物组与生产表型的互作研究已经成为国际研究热点。综述了2016年动物胃肠道微生物组学研究取得的十项重要成果,这些成果通过组学方法,研究了瘤胃纤维分解菌和尿素分解菌的功能基因多样性,揭示了微生物群落与日粮营养素、宿主基因型、环境的互作关系,阐明了反刍动物生产表型相关的瘤胃微生物种类和功能;首次构建猪肠道微生物组参考基因集,解析猪全肠道黏膜微生物组成,阐明了猪增重相关肠道微生物种类。这十大亮点成果将为国内动物营养学家开展动物胃肠道微生物组学研究提供参考。     

Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance

Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host–microbe variation and coevolution, microbial biogeography, and disease risk, and have important implications for the use of animal models in studies of human sexual and reproductive diseases.     

Epigenome-Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease

Preterm birth is the leading cause of infant morbidity and mortality. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease affecting primarily premature infants, which can be lethal. Microbial intestinal colonization may alter epigenetic signatures of the immature gut establishing inflammatory and barrier properties predisposing to the development of NEC. We hypothesize that a crosstalk exists between the epigenome of the host and the initial intestinal colonizing microbiota at critical neonatal stages. By exposing immature enterocytes to probiotic and pathogenic bacteria, we showed over 200 regions of differential DNA modification, which were specific for each exposure. Reciprocally, using a mouse model of prenatal exposure to dexamethasone we demonstrated that antenatal treatment with glucocorticoids alters the epigenome of the host. We investigated the effects on the expression profiles of genes associated with inflammatory responses and intestinal barrier by qPCR-based gene expression array and verified the DNA modification changes in 5 candidate genes by quantitative methylation specific PCR (qMSP). Importantly, by 16S RNA sequencing-based phylogenetic analysis of intestinal bacteria in mice at 2 weeks of life, we showed that epigenome changes conditioned early microbiota colonization leading to differential bacterial colonization at different taxonomic levels. Our findings support a novel conceptual framework in which epigenetic changes induced by intrauterine influences affect early microbial colonization and intestinal development, which may alter disease susceptibility.     

A descriptive analysis of gut microbiota composition in differentially reared infant rhesus monkeys (Macaca mulatta) across the first 6 months of life

The gastrointestinal microbiome is recognized as a critical component in host immune function, physiology, and behavior. Early life experiences that alter diet and social contact also influence these outcomes. Despite the growing number of studies in this area, no studies to date have examined the contribution of early life experiences on the gut microbiome in infants across development. Such studies are important for understanding the biological and environmental factors that contribute to optimal gut microbial colonization and subsequent health. We studied infant rhesus monkeys (Macaca mulatta) across the first 6 months of life that were pseudo‐randomly assigned to one of two different rearing conditions at birth: mother‐peer‐reared (MPR), in which infants were reared in social groups with many other adults and peers and nursed on their mothers, or nursery‐reared (NR), in which infants were reared by human caregivers, fed formula, and given daily social contact with peers. We analyzed the microbiome from rectal swabs (total N = 97; MPR = 43, NR = 54) taken on the day of birth and at postnatal Days 14, 30, 90, and 180 using 16S rRNA gene sequencing. Bacterial composition differences were evident as early as 14 days, with MPR infants exhibiting a lower abundance of Bifidobacterium and a higher abundance of Bacteroides than NR infants. The most marked differences were observed at 90 days, when Bifidobacterium, Lactobacillus, Streptococcus, Bacteroides, Clostridium, and Prevotella differed across rearing groups. By Day 180, no differences in the relative abundances of the bacteria of interest were observed. These novel findings in developing primate neonates indicate that the early social environment as well as diet influence gut microbiota composition very early in life. These results also lay the groundwork for mechanistic studies examining the effects of early experiences on gut microbiota across development with the ultimate goal of understanding the clinical significance of developmental changes.