Microbiome alterations in HIV infection a review

Recent developments in molecular techniques have allowed researchers to identify previously uncultured organisms, which has propelled a vast expansion of our knowledge regarding our commensal microbiota. Interest in the microbiome specific to HIV grew from earlier findings suggesting that bacterial translocation from the intestines is the cause of persistent immune activation despite effective viral suppression with antiretroviral therapy (ART). Studies of SIV infected primates have demonstrated that Proteobacteria preferentially translocate and that mucosal immunity can be restored with probiotics. Pathogenic SIV infection results in a massive expansion of the virome, whereas non‐pathogenic SIV infection does not. Human HIV infected cohorts have been shown to have microbiota distinctive from that of HIV negative controls and efforts to restore the intestinal microbiome via probiotics have often had positive results on host markers. The microbiota of the genital tract may play a significant role in acquisition and transmission of HIV. Modification of commensal microbial communities likely represents an important therapeutic adjunct to treatment of HIV. Here we review the literature regarding human microbiome in HIV infection.     

Potential role of chitinases and chitin-binding proteins in host-microbial interactions during the development of intestinal inflammation

The small and large intestines contain an abundance of luminal antigens derived from food products and enteric microorganisms. The function of intestinal epithelial cells is tightly regulated by several factors produced by enteric bacteria and the epithelial cells themselves. Epithelial cells actively participate in regulating the homeostasis of intestine, and failure of this function leads to abnormal and host-microbial interactions resulting in the development of intestinal inflammation. Major determinants of host susceptibility against luminal commensal bacteria include genes regulating mucosal immune responses, intestinal barrier function and microbial defense. Of note, it has been postulated that commensal bacterial adhesion and invasion on/into host cells may be strongly involved in the pathogenesis of inflammatory bowel disease (IBD). During the intestinal inflammation, the composition of the commensal flora is altered, with increased population of aggressive and detrimental bacteria and decreased populations of protective bacteria. In fact, some pathogenic bacteria, including Adherent-Invasive Escherichia coli, Listeria monocytogenes and Vibrio cholerae are likely to initiate their adhesion to the host cells by expressing accessory molecules such as chitinases and/or chitin-binding proteins on themselves. In addition, several inducible molecules (e.g., chitinase 3-like 1, CEACAM6) are also induced on the host cells (e.g. epithelial cells, lamina proprial macrophages) under inflammatory conditions, and are actively participated in the host-microbial interactions. In this review, we will summarize and discuss the potential roles of these important molecules during the development of acute and chronic inflammatory conditions.     

Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease

Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body’s response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.     

Human Pharyngeal Microbiome May Play A Protective Role in Respiratory Tract Infections

The human pharyngeal microbiome, which resides at the juncture of digestive and respiratory tracts, may have an active role in the prevention of respiratory tract infections, similar to the actions of the intestinal microbiome against enteric infections. Recent studies have demonstrated that the pharyngeal microbiome comprises an abundance of bacterial species that interacts with the local epithelial and immune cells, and together, they form a unique micro-ecological system. Most of the microbial species in microbiomes are obligate symbionts constantly adapting to their unique surroundings. Indigenous commensal species are capable of both maintaining dominance and evoking host immune responses to eliminate invading species. Temporary damage to the pharyngeal microbiome due to the impaired local epithelia is also considered an important predisposing risk factor for infections. Therefore, reinforcement of microbiome homeostasis to prevent invasion of infection-prone species would provide a novel treatment strategy in addition to antibiotic treatment and vaccination. Hence continued research efforts on evaluating probiotic treatment and developing appropriate procedures are necessary to both prevent and treat respiratory infections.     

The intestinal flora: the scales without the sword

The intestine is colonised by a vast population of resident bacteria which have established mutualistic relationships with their host throughout evolution, progressing from commensalism to symbiotic interactions. Intestinal bacteria benefit from resources available in their host, but reciprocally provide advantages to their host, by supplying enzymatic activities not encoded in the host genome, by promoting maturation of the intestine and of the gut associated immune system as well as by modifying the host metabolism. The commensal bacteria, although deprived of pathogenic attributes, might however become a danger for the host in case of translocation, acquisition of pathogenic features or via the inappropriate activation of intestinal inflammation. Remarkably, the commensal flora promotes the onset of innate and adaptive immune defences which, in turn, allow to set up a subtle balance between the host and the flora that promotes the symbiosis.     

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.     

Characterization of the human DNA gut virome across populations with different subsistence strategies and geographical origin

It is a matter of fact that the human gut microbiome also includes a non‐bacterial fraction represented by eukaryotic cells and viruses. To further explore the gut microbiome variation in human populations, here we characterized the human DNA viral community from publicly available gut metagenome data sets from human populations with different geographical origin and lifestyle. In particular, such data sets encompass microbiome information from two western urban societies (USA and Italy), as well as two traditional hunter‐gatherer communities (the Hadza from Tanzania and Matses from Peru) and one pre‐agricultural tribe (Tunapuco from Peru). Our results allowed for the first taxonomic reconstruction of the complex viral metacommunities within the human gut. The core virome structure included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses and anelloviruses. Using Random Forests and a co‐occurrence analysis approach, we identified the viruses that distinguished populations according to their geographical origin and/or lifestyle. This paves the way for new research aimed at investigating the biological role of the gut virome in human physiology, and the importance of our viral counterpart in the microbiome‐host co‐evolutionary process.     

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。     

人体肠道病毒组学研究进展

人体微生物组计划开展近10年来,大量的研究显示人体微生物通过各种方式深刻地影响着人体健康。人体肠道内丰富多样的病毒构成了肠道病毒组,是人体微生物组的重要组成部分,和人体健康密切相关。本文综述了近些年国际上人体肠道病毒组研究的最新进展,分别从人体肠道病毒组的组成特征、肠道病毒组-细菌组-人体间的相互作用及其对人体健康的影响、病毒组研究的技术策略及挑战等方面进行了论述,探讨了肠道病毒组在人体疾病预防和治疗领域应用的可行性。     

Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.     

The role of microbiota in infectious disease

The intestine harbors an ecosystem composed of the intestinal mucosa and the commensal microbiota. The microbiota fosters development, aids digestion and protects host cells from pathogens - a function referred to as colonization resistance. Little is known about the molecular basis of colonization resistance and how it can be overcome by enteropathogenic bacteria. Recently, studies on inflammatory bowel diseases and on animal models for enteric infection have provided new insights into colonization resistance. Gut inflammation changes microbiota composition, disrupts colonization resistance and enhances pathogen growth. Thus, some pathogens can benefit from inflammatory defenses. This new paradigm will enable the study of host factors enhancing or inhibiting bacterial growth in health and disease.     

Characterization of the rat oral microbiome and the effects of dietary nitrate

The nitrate–nitrite–NO pathway to nitric oxide (NO) production is a symbiotic pathway in mammals that is dependent on nitrate reducing oral commensal bacteria. Studies suggest that by contributing NO to the mammalian host, the oral microbiome helps maintain cardiovascular health. To begin to understand how changes in oral microbiota affect physiological functions such as blood pressure, we have characterized the Wistar rat nitrate reducing oral microbiome. Using 16S rRNA gene sequencing and analysis we compare the native Wistar rat tongue microbiome to that of healthy humans and to that of rats with sodium nitrate and chlorhexidine mouthwash treatments. We demonstrate that the rat tongue microbiome is less diverse than the human tongue microbiome, but that the physiological activity is comparable, as sodium nitrate supplementation significantly lowered diastolic blood pressure in Wistar rats and also lowers blood pressure (diastolic and systolic) in humans. We also show for the first time that sodium nitrate supplementation alters the abundance of specific bacterial species on the tongue. Our results suggest that the changes in oral nitrate reducing bacteria may affect nitric oxide availability and physiological functions such as blood pressure. Understanding individual changes in human oral microbiome may offer novel dietary approaches to restore NO availability and blood pressure.     

Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics

Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host–microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host–microbe interaction and successful commensalism to institute a human gut microbiome.     

Commensal bacteria modulate cullin-dependent signaling via generation of reactive oxygen species

The resident prokaryotic microflora of the mammalian intestine influences diverse homeostatic functions of the gut, including regulation of cellular growth and immune responses; however, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. We have shown that bacterial coculture with intestinal epithelial cells modulates ubiquitin-mediated degradation of important signaling intermediates, including beta-catenin and the NF-kappaB inhibitor IkappaB-alpha. Ubiquitination of these proteins as well as others is catalyzed by the SCF(betaTrCP) ubiquitin ligase, which itself requires regulated modification of the cullin-1 subunit by the ubiquitin-like protein NEDD8. Here we show that epithelia contacted by enteric commensal bacteria in vitro and in vivo rapidly generate reactive oxygen species (ROS). Bacterially induced ROS causes oxidative inactivation of the catalytic cysteine residue of Ubc12, the NEDD8-conjugating enzyme, resulting in complete but transient loss of cullin-1 neddylation and consequent effects on NF-kappaB and beta-catenin signaling. Our results demonstrate that commensal bacteria directly modulate a critical control point of the ubiquitin-proteasome system, and suggest how enteric commensal bacterial flora influences the regulatory pathways of the mammalian intestinal epithelia.     

Next steps after 15 stimulating years of human gut microbiome research

Gut microbiome research has bloomed over the past 15 years. We have learnt a lot about the complex microbial communities that colonize our intestine. Promising avenues of research and microbiome-based applications are being implemented, with the goal of sustaining host health and applying personalized disease management strategies. Despite this exciting outlook, many fundamental questions about enteric microbial ecosystems remain to be answered. Organizational measures will also need to be taken to optimize the outcome of discoveries happening at an extremely rapid pace. This article highlights our own view of the field and perspectives for the next 15 years.     

Microbes,the gut and ankylosing spondylitis

It is increasingly clear that the interaction between host and microbiome profoundly affects health. There are 10 times more bacteria in and on our bodies than the total of our own cells, and the human intestine contains approximately 100 trillion bacteria. Interrogation of microbial communities by using classic microbiology techniques offers a very restricted view of these communities, allowing us to see only what we can grow in isolation. However, recent advances in sequencing technologies have greatly facilitated systematic and comprehensive studies of the role of the microbiome in human health and disease. Comprehensive understanding of our microbiome will enhance understanding of disease pathogenesis, which in turn may lead to rationally targeted therapy for a number of conditions, including autoimmunity.     

Dynamic gut microbiome across life history of the malaria mosquito Anopheles gambiae in Kenya

The mosquito gut represents an ecosystem that accommodates a complex, intimately associated microbiome. It is increasingly clear that the gut microbiome influences a wide variety of host traits, such as fitness and immunity. Understanding the microbial community structure and its dynamics across mosquito life is a prerequisite for comprehending the symbiotic relationship between the mosquito and its gut microbial residents. Here we characterized gut bacterial communities across larvae, pupae and adults of Anopheles gambiae reared in semi-natural habitats in Kenya by pyrosequencing bacterial 16S rRNA fragments. Immatures and adults showed distinctive gut community structures. Photosynthetic Cyanobacteria were predominant in the larval and pupal guts while Proteobacteria and Bacteroidetes dominated the adult guts, with core taxa of Enterobacteriaceae and Flavobacteriaceae. At the adult stage, diet regime (sugar meal and blood meal) significantly affects the microbial structure. Intriguingly, blood meals drastically reduced the community diversity and favored enteric bacteria. Comparative genomic analysis revealed that the enriched enteric bacteria possess large genetic redox capacity of coping with oxidative and nitrosative stresses that are associated with the catabolism of blood meal, suggesting a beneficial role in maintaining gut redox homeostasis. Interestingly, gut community structure was similar in the adult stage between the field and laboratory mosquitoes, indicating that mosquito gut is a selective eco-environment for its microbiome. This comprehensive gut metatgenomic profile suggests a concerted symbiotic genetic association between gut inhabitants and host.     

Citrobacter rodentium of mice and man

The major classes of enteric bacteria harbour a conserved core genomic structure, common to both commensal and pathogenic strains, that is most likely optimized to a life style involving colonization of the host intestine and transmission via the environment. In pathogenic bacteria this core genome framework is decorated with novel genetic islands that are often associated with adaptive phenotypes such as virulence. This classical genome organization is well illustrated by a group of extracellular enteric pathogens, which includes enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Citrobacter rodentium, all of which use attaching and effacing (A/E) lesion formation as a major mechanism of tissue targeting and infection. Both EHEC and EPEC are poorly pathogenic in mice but infect humans and domestic animals. In contrast, C. rodentium is a natural mouse pathogen that is related to E. coli, hence providing an excellent in vivo model for A/E lesion forming pathogens. C. rodentium also provides a model of infections that are mainly restricted to the lumen of the intestine. The mechanism's by which the immune system deals with such infections has become a topic of great interest in recent years. Here we review the literature of C. rodentium from its emergence in the mid-1960s to the most contemporary reports of colonization, pathogenesis, transmission and immunity.     

Engineering the human gut commensal Bacteroides thetaiotaomicron with synthetic biology

The role of the microbiome in health and disease is attracting the attention of researchers seeking to engineer microorganisms for diagnostic and therapeutic applications. Recent progress in synthetic biology may enable the dissection of host–microbiota interactions. Sophisticated genetic circuits that can sense, compute, memorize, and respond to signals have been developed for the stable commensal bacterium Bacteroides thetaiotaomicron, dominant in the human gut. In this review, we highlight recent advances in expanding the genetic toolkit for B. thetaiotaomicron and foresee several applications of this species for microbiome engineering. We provide our perspective on the challenges and future opportunities for the engineering of human gut-associated bacteria as living therapeutic agents.