Primate microbial endocrinology: An uncharted frontier

Gut microbial communities communicate bidirectionally with the brain through endocrine, immune, and neural signaling, influencing the physiology and behavior of hosts. The emerging field of microbial endocrinology offers innovative perspectives and methods to analyze host‐microbe relationships with relevance to primate ecology, evolution, and conservation. Herein we briefly summarize key findings from microbial endocrinology and explore how applications of a similar framework could inform our understanding of primate stress and reproductive physiology and behavior. We conclude with three guiding hypotheses to further investigate endocrine signaling between gut microbes and the host: (a) host‐microbe communication systems promote microbe‐mediated stability, in which the microbes are using endocrine signaling from the host to maintain a functioning habitat for their own fitness, (b) host‐microbe communication systems promote host‐mediated stability, in which the host uses the endocrine system to monitor microbial communities and alter these communities to maintain stability, or (c) host‐microbe systems are simply the product of coincidental cross‐talk between the host and microbes due to similar molecules from shared ancestry. Utilizing theory and methodology for studying relationships between the microbiome, hormones, and behavior of wild primates is an uncharted frontier with many promising insights when applied to primatology.     

More than words: the chemistry behind the interactions in the plant holobiont

Plants and microbes have evolved sophisticated ways to communicate and coexist. The simplest interactions that occur in plant-associated habitats, i.e., those involved in disease detection, depend on the production of microbial pathogenic and virulence factors and the host's evolved immunological response. In contrast, microbes can also be beneficial for their host plants in a number of ways, including fighting pathogens and promoting plant growth. In order to clarify the mechanisms directly involved in these various plant–microbe interactions, we must still deepen our understanding of how these interkingdom communication systems, which are constantly modulated by resident microbial activity, are established and, most importantly, how their effects can span physically separated plant compartments. Efforts in this direction have revealed a complex and interconnected network of molecules and associated metabolic pathways that modulate plant–microbe and microbe–microbe communication pathways to regulate diverse ecological responses. Once sufficiently understood, these pathways will be biotechnologically exploitable, for example, in the use of beneficial microbes in sustainable agriculture. The aim of this review is to present the latest findings on the dazzlingly diverse arsenal of molecules that efficiently mediate specific microbe–microbe and microbe–plant communication pathways during plant development and on different plant organs.     

Microbial endocrinology: how stress influences susceptibility to infection

A holistic approach to understanding the mechanisms by which stress influences the pathogenesis of infectious disease has resulted in the development of the field of microbial endocrinology. This transdisciplinary field represents the intersection of microbiology with mammalian endocrinology and neurophysiology, and is based on the tenet that microorganisms have evolved systems for using neurohormones, which are widely distributed throughout nature, as environmental cues to initiate growth and pathogenic processes. This review reveals that responsiveness to human stress hormones is widespread in the microbial world and documents recent advances in microbial endocrinology.     

Microbial Endocrinology

Microbial Endocrinology is a new microbiology research discipline that represents the intersection of microbiology and endocrinology with neurophysiology. It has as its main tenet that through their long co-existence with animals and plants, micro-organisms have evolved sensory systems for detecting host-associated hormones. These sensing systems allow the microbe to determine that they are within proximity of a suitable host, and that is time to initiate expression of genes involved in host colonisation. Microbial Endocrinology therefore provides a new paradigm with which to examine and understand the interactions of micro-organisms with their host under conditions present in both health and disease. This article will focus on microbial interactions with the fight and flight family of catecholamine stress hormones.     

Pushing the envelope: extracytoplasmic stress responses in bacterial pathogens

Despite being nutrient rich, the tissues and fluids of vertebrates are hostile to microorganisms, and most bacteria that attempt to take advantage of this environment are rapidly eliminated by host defences. Pathogens have evolved various means to promote their survival in host tissues, including stress responses that enable bacteria to sense and adapt to adverse conditions. Many different stress responses have been described, some of which are responsive to one or a small number of cues, whereas others are activated by a broad range of insults. The surface layers of pathogenic bacteria directly interface with the host and can bear the brunt of the attack by the host armoury. Several stress systems that respond to perturbations in the microbial cell outside of the cytoplasm have been described and are known collectively as extracytoplasmic or envelope stress responses (ESRs). Here, we review the role of the ESRs in the pathogenesis of Gram-negative bacterial pathogens.     

Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics

I hypothesize here that the ability of probiotics to synthesize neuroactive compounds provides a unifying microbial endocrinology-based mechanism to explain the hitherto incompletely understood action of commensal microbiota that affect the host's gastrointestinal and psychological health. Once ingested, probiotics enter an interactive environment encompassing microbiological, immunological, and neurophysiological components. By utilizing a trans-disciplinary framework known as microbial endocrinology, mechanisms that would otherwise not be considered become apparent since any candidate would need to be shared among all three components. The range of neurochemicals produced by probiotics includes neurochemicals for which receptor-based targets on immune and neuronal elements (intestinal and extra-intestinal) have been well characterized. Production of neurochemicals by probiotics therefore allows for their consideration as delivery vehicles for neuroactive compounds. This unifying microbial endocrinology-based hypothesis, which may facilitate the selection and design of probiotics for clinical use, also highlights the largely unrecognized role of neuroscience in understanding how microbes may influence health.     

Role of neuromediators in the functioning of the human microbiota: “Business talks” among microorganisms and the microbiota-host dialogue

Current concepts concerning the social behavior of microorganisms inhabiting the human gastrointestinal (GI) tract and their role in the formation of integrated supracellular structures and in intercellular communication in the host–microbiota system are reviewed. The analysis of the literature data and of the results obtained by the authors indicates an important role of neuromediators (biogenic amines, amino acids, peptides, and nitric oxide) in intra- and interspecies microbial communication, as well as in the microbiota–host dialogue. The role of this dialogue for human health, its effect on the human psyche and social behavior, and the possibility of construction of probiotic preparations with a target-oriented neurochemical effect are discussed.     

The cryptic role of biodiversity in the emergence of host–microbial mutualisms

The persistence of mutualisms in host‐microbial – or holobiont – systems is difficult to explain because microbial mutualists, who bear the costs of providing benefits to their host, are always prone to being competitively displaced by non‐mutualist ‘cheater’ species. This disruptive effect of competition is expected to be particularly strong when the benefits provided by the mutualists entail costs such as reduced competitive ability. Using a metacommunity model, we show that competition between multiple cheaters within the host's microbiome, when combined with the spatial structure of host–microbial interactions, can have a constructive rather than a disruptive effect by allowing the emergence and maintenance of mutualistic microorganisms within the host. These results indicate that many of the microorganisms inhabiting a host's microbiome, including those that would otherwise be considered opportunistic or even potential pathogens, play a cryptic yet critical role in promoting the health and persistence of the holobiont across spatial scales.     

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.     

The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept

Along the human gastrointestinal tract, microorganisms are confronted with multiple barriers. Besides selective physical conditions, the epithelium is regularly replaced and covered with a protective mucus layer trapping immune molecules. Recent insights into host defense strategies show that the host selects the intestinal microbiota, particularly the mucosa-associated microbial community. In this context, humans coevolved with thousands of intestinal microbial species that have adapted to provide host benefits, while avoiding pathogenic behavior that might destabilize their host interaction. While mucosal microorganisms would be crucial for immunological priming, luminal microorganisms would be important for nutrient digestion. Further, we propose that the intestinal microorganisms also coevolved with each other, leading to coherently organized, resilient microbial associations. During disturbances, functionally redundant members become more abundant and are crucial for preserving community functionality. The outside of the mucus layer, where host defense molecules are more diluted, could serve as an environment where microorganisms are protected from disturbances in the lumen and from where they can recolonize the lumen after perturbations. This might explain the remarkable temporal stability of microbial communities. Finally, commensals that become renegade or a decreased exposure to essential coevolved microorganisms may cause particular health problems such as inflammatory bowel diseases, obesity or allergies.     

Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens

The gastrointestinal tract is a complex ecosystem that associates a resident microbiota and cells of various phenotypes lining the epithelial wall expressing complex metabolic activities. The resident microbiota in the digestive tract is a heterogeneous microbial ecosystem containing up to 1 x 10(14) colony-forming units (CFUs) of bacteria. The intestinal microbiota plays an important role in normal gut function and maintaining host health. The host is protected from attack by potentially harmful microbial microorganisms by the physical and chemical barriers created by the gastrointestinal epithelium. The cells lining the gastrointestinal epithelium and the resident microbiota are two partners that properly and/or synergistically function to promote an efficient host system of defence. The gastrointestinal cells that make up the epithelium, provide a physical barrier that protects the host against the unwanted intrusion of microorganisms into the gastrointestinal microbiota, and against the penetration of harmful microorganisms which usurp the cellular molecules and signalling pathways of the host to become pathogenic. One of the basic physiological functions of the resident microbiota is that it functions as a microbial barrier against microbial pathogens. The mechanisms by which the species of the microbiota exert this barrier effect remain largely to be determined. There is increasing evidence that lactobacilli and bifidobacteria, which inhabit the gastrointestinal microbiota, develop antimicrobial activities that participate in the host's gastrointestinal system of defence. The objective of this review is to analyze the in vitro and in vivo experimental and clinical studies in which the antimicrobial activities of selected lactobacilli and bifidobacteria strains have been documented.     

The zebrafish as a model for gastrointestinal tract–microbe interactions

The zebrafish (Danio rerio) has become a widely used vertebrate model for bacterial, fungal, viral, and protozoan infections. Due to its genetic tractability, large clutch sizes, ease of manipulation, and optical transparency during early life stages, it is a particularly useful model to address questions about the cellular microbiology of host–microbe interactions. Although its use as a model for systemic infections, as well as infections localised to the hindbrain and swimbladder having been thoroughly reviewed, studies focusing on host–microbe interactions in the zebrafish gastrointestinal tract have been neglected. Here, we summarise recent findings regarding the developmental and immune biology of the gastrointestinal tract, drawing parallels to mammalian systems. We discuss the use of adult and larval zebrafish as models for gastrointestinal infections, and more generally, for studies of host–microbe interactions in the gut.     

Host‐microbiome interactions in acute and chronic respiratory infections

Respiratory infection is a leading cause of global morbidity and mortality. Understanding the factors that influence risk and outcome of these infections is essential to improving care. We increasingly understand that interactions between the microbial residents of our mucosal surfaces and host regulatory systems is fundamental to shaping local and systemic immunity. These mechanisms are most well defined in the gastrointestinal tract, however analogous systems also occur in the airways. Moreover, we now appreciate that the host–microbiota interactions at a given mucosal surface influence systemic host processes, in turn, affecting the course of infection at other anatomical sites. This review discusses the mechanisms by which the respiratory microbiome influences acute and chronic airway disease and examines the contribution of cross‐talk between the gastrointestinal and respiratory compartments to microbe–mucosa interactions.     

The Enteric Two‐Step: nutritional strategies of bacterial pathogens within the gut

The gut microbiota is a dense and diverse microbial community governed by dynamic microbe–microbe and microbe–host interactions, the status of which influences whether enteric pathogens can cause disease. Here we review recent insights into the key roles that nutrients play in bacterial pathogen exploitation of the gut microbial ecosystem. We synthesize recent findings to support a five‐stage model describing the transition between a healthy microbiota and one dominated by a pathogen and disease. Within this five‐stage model, two stages are critical to the pathogen: (i) an initial expansion phase that must occur in the absence of pathogen‐induced inflammation, followed by (ii) pathogen‐promoting physiological changes such as inflammation and diarrhoea. We discuss how this emerging paradigm of pathogen life within the lumen of the gut is giving rise to novel therapeutic strategies.     

Emerging roles of low-molecular-weight thiols at the host–microbe interface

Low-molecular-weight (LMW) thiols are an abundant class of cysteine-derived small molecules found in all forms of life that maintain reducing conditions within cells. While their contributions to cellular redox homeostasis are well established, LMW thiols can also mediate other aspects of cellular physiology, including intercellular interactions between microbial and host cells. Here we discuss emerging roles for these redox-active metabolites at the host–microbe interface. We begin by providing an overview of chemical and computational approaches to LMW-thiol discovery. Next, we highlight mechanisms of virulence regulation by LMW thiols in infected cells. Finally, we describe how microbial metabolism of these compounds may influence host physiology.     

Myrothins A–F from Endophytic Fungus Myrothecium sp. BS-31 Harbored in Panax notoginseng

Endophytic fungi play important roles for host's stress tolerance including invasion by pathogenic microbes. Small molecules are common weapons in the microbe–microbe interactions. Panax notoginseng is a widely used traditional Chinese medicinal plant and harbors many endophytes, some exert functions against pathogens. Here, we report six new compounds named myrothins A–F ( 1 – 6 ) produced by Myrothecium sp. BS-31, an endophyte isolated from P. notoginseng, and their antifungal activities against pathogenic fungi causing host root-rot disease. Their structures were elucidated with analysis of spectroscopic data including 1D and 2D NMR, HR-ESI-MS. Myrothins B ( 2 ) and E ( 5 ) showed the weak activity against Fusarium oxysporum and Phoma herbarum, and myrothins F ( 6 ) showed weak activity against F. oxysporum.     

Effects of polymicrobial communities on host immunity and response

Microorganisms grow as members of microbial communities in unique niches, such as the mucosal surfaces of the human body. These microbial communities, containing both commensals and opportunistic pathogens, serve to keep individual pathogens 'in check' through a variety of mechanisms and complex interactions, both between the microorganisms themselves and the microorganisms and the host. Recent studies shed new light on the diversity of microorganisms that form the human microbial communities and the interactions these microbial communities have with the host to stimulate immune responses. This occurs through their recognition by dendritic cells or their ability to induce differential cytokine and defensin profiles. The differential induction of defensins by commensals and pathogens and the ability of the induced defensins to interact with the antigens from these microorganisms may attenuate proinflammatory signaling and trigger adaptive immune responses to microbial antigens in a multistep process. Such an activity may be a mechanism that the host uses to sense what is on its mucosal surfaces, as well as to differentiate among commensals and pathogens.     

AM真菌在植物病虫害生物防治中的作用机制

丛枝菌根(Arbuscular Mycorrhizae,AM)真菌是一类广泛分布于土壤生态系统中的有益微生物,能与大约80%的陆生高等植物形成共生体。由土传病原物侵染引起的土传病害被植物病理学界认定为最难防治的病害之一。研究表明,AM真菌能够拮抗由真菌、线虫、细菌等病原体引起的土传性植物病害,诱导宿主植物增强对病虫害的耐/抗病性。当前,利用AM真菌开展病虫害的生物防治已经引起生态学家和植物病理学家的广泛关注。基于此,围绕AM真菌在植物病虫害生物防治中的最新研究进展,从AM真菌改变植物根系形态结构、调节次生代谢产物的合成、改善植物根际微环境、与病原微生物直接竞争入侵位点和营养分配、诱导植株体内抗病防御体系的形成等角度,探究AM真菌在植物病虫害防治中的作用机理,以期为利用AM真菌开展植物病虫害的生物防治提供理论依据,并对本领域未来的发展方向和应用前景进行展望。     

Microbial considerations in genetically engineered mouse research

Microbial infections have long been of concern to scientists using laboratory rodents because of their potential to confound and invalidate research. With the explosion of genetically engineered mice (GEM), new concerns over the impact of microbial agents have emerged because these rodents in many cases are more susceptible to disease than their inbred or outbred counterparts. Moreover, interaction between microbe and host and the resulting manifestation of disease conceivably differ between GEM and their inbred and outbred counterparts. As a result, infections may alter the GEM phenotype and confound interpretation of results and conclusions about mutated gene function. In addition, because GEM are expensive to produce and maintain, contamination by pathogens or opportunists has severe economic consequences. This review addresses how microbial infections may influence phenotype, how immunomodulation of the host as the result of induced mutations may modify host susceptibility to microbial infections, how novel host:microbe interactions have led to the development of new animal models for disease, how phenotype changes have led to the discovery of new pathogens, and new challenges associated with prevention and control of microbial infections in GEM. Although the focus is on naturally occurring infections, extensive literature on the use of GEM in studies of microbial pathogenesis also exists, and the reader is referred to this literature if microbial infection is a suspected culprit in phenotype alteration.