Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.

BACKGROUND: Following descriptive studies on skin microbiota in health and disease, mechanistic studies on the interplay between skin and microbes are on the rise, for which experimental models are in great demand. Here, we present a novel methodology for microbial colonization of organotypic skin and analysis thereof. RESULTS: An inoculation device ensured a standardized application area on the stratum corneum and a homogenous distribution of bacteria, while preventing infection of the basolateral culture medium even during prolonged culture periods for up to 2 weeks at a specific culture temperature and humidity. Hereby, host-microbe interactions and antibiotic interventions could be studied, revealing diverse host responses to various skin-related bacteria and pathogens. CONCLUSIONS: Our methodology is easily transferable to a wide variety of organotypic skin or mucosal models and different microbes at every cell culture facility at low costs. We envision that this study will kick-start skin microbiome studies using human organotypic skin cultures, providing a powerful alternative to experimental animal models in pre-clinical research. Video Abstract.

Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies.

Many systemically administered cancer therapies exhibit dose-limiting toxicities that reduce their effectiveness. To increase efficacy, bacterial delivery platforms have been developed that improve safety and prolong treatment. Bacteria are a unique class of therapy that selectively colonizes most solid tumors. As delivery vehicles, bacteria have been genetically modified to express a range of therapies that match multiple cancer indications. In this review, we describe a modular "build-a-bug" method that focuses on five design characteristics: bacterial strain (chassis), therapeutic compound, delivery method, immune-modulating features, and genetic control circuits. We emphasize how fundamental research into gut microbe pathogenesis has created safe bacterial therapies, some of which have entered clinical trials. The genomes of gut microbes are fertile grounds for discovery of components to improve delivery and modulate host immune responses. Future work coupling these delivery vehicles with insights from gut microbes could lead to the next generation of microbial cancer therapy.

Race between virus and inflammasomes: inhibition or escape, intervention and therapy.

The inflammasome is a multiprotein complex that further regulates cell pyroptosis and inflammation by activating caspase-1. The assembly and activation of inflammasome are associated with a variety of diseases. Accumulative studies have shown that inflammasome is a key modulator of the host's defense response to viral infection. Indeed, it has been established that activation of inflammasome occurs during viral infection. At the same time, the host has evolved a variety of corresponding mechanisms to inhibit unnecessary inflammasome activation. Therefore, here, we review and summarize the latest research progress on the interaction between inflammosomes and viruses, highlight the assembly and activation of inflammosome in related cells after viral infection, as well as the corresponding molecular regulatory mechanisms, and elucidate the effects of this activation on virus immune escape and host innate and adaptive immune defenses. Finally, we also discuss the potential therapeutic strategies to prevent and/or ameliorate viral infection-related diseases via targeting inflammasomes and its products.

L-arginine metabolism as pivotal interface of mutual host-microbe interactions in the gut.

L-arginine (L-arg) is a versatile amino acid and a central intestinal metabolite in mammalian and microbial organisms. Thus, L-arg participates as precursor of multiple metabolic pathways in the regulation of cell division and growth. It also serves as a source of carbon, nitrogen, and energy or as a substrate for protein synthesis. Consequently, L-arg can simultaneously modify mammalian immune functions, intraluminal metabolism, intestinal microbiota, and microbial pathogenesis. While dietary intake, protein turnover or de novo synthesis usually supply L-arg in sufficient amounts, the expression of several key enzymes of L-arg metabolism can change rapidly and dramatically following inflammation, sepsis, or injury. Consequently, the availability of L-arg can be restricted due to increased catabolism, transforming L-arg into an essential amino acid. Here, we review the enzymatic pathways of L-arg metabolism in microbial and mammalian cells and their role in immune function, intraluminal metabolism, colonization resistance, and microbial pathogenesis in the gut.

Dissecting skin microbiota and microenvironment for the development of therapeutic strategies.

The skin is a pivotal barrier between the human body and the environment, and is a habitat for numerous microorganisms. While host-microbiota interactions in the skin are essential for homeostasis, disturbances in microbial composition and the abnormal growth of certain bacteria are associated with various diseases. Here, we identify strains and communities of skin commensals that contribute to or impair skin barrier function. Furthermore, we discuss the skin microenvironments suitable for specific microbiota that exert therapeutic effects and suggest focus areas for the prospective development of therapeutic strategies using bacterial agents. Finally, we highlight recent efforts to treat skin diseases associated with live bacteria.

An overview on monkeypox virus: Pathogenesis, transmission, host interaction and therapeutics.

Orthopoxvirus is one of the most notorious genus amongst the Poxviridae family. Monkeypox (MP) is a zoonotic disease that has been spreading throughout Africa. The spread is global, and incidence rates are increasing daily. The spread of the virus is rapid due to human-to-human and animals-to-human transmission. World Health Organization (WHO) has declared monkeypox virus (MPV) as a global health emergency. Since treatment options are limited, it is essential to know the modes of transmission and symptoms to stop disease spread. The information from host-virus interactions revealed significantly expressed genes that are important for the progression of the MP infection. In this review, we highlighted the MP virus structure, transmission modes, and available therapeutic options. Furthermore, this review provides insights for the scientific community to extend their research work in this field.

Over supplementation with vitamin B12 alters microbe-host interactions in the gut leading to accelerated Citrobacter rodentium colonization and pathogenesis in mice.

BACKGROUND: Vitamin B12 supplements typically contain doses that far exceed the recommended daily amount, and high exposures are generally considered safe. Competitive and syntrophic interactions for B12 exist between microbes in the gut. Yet, to what extent excessive levels contribute to the activities of the gut microbiota remains unclear. The objective of this study was to evaluate the effect of B12 on microbial ecology using a B12 supplemented mouse model with Citrobacter rodentium, a mouse-specific pathogen. Mice were fed a standard chow diet and received either water or water supplemented with B12 (cyanocobalamin: ~120 µg/day), which equates to approximately 25 mg in humans. Infection severity was determined by body weight, pathogen load, and histopathologic scoring. Host biomarkers of inflammation were assessed in the colon before and after the pathogen challenge. RESULTS: Cyanocobalamin supplementation enhanced pathogen colonization at day 1 (P < 0.05) and day 3 (P < 0.01) postinfection. The impact of B12 on gut microbial communities, although minor, was distinct and attributed to the changes in the Lachnospiraceae populations and reduced alpha diversity. Cyanocobalamin treatment disrupted the activity of the low-abundance community members of the gut microbiota. It enhanced the amount of interleukin-12 p40 subunit protein (IL12/23p40; P < 0.001) and interleukin-17a (IL-17A; P < 0.05) in the colon of naïve mice. This immune phenotype was microbe dependent, and the response varied based on the baseline microbiota. The cecal metatranscriptome revealed that excessive cyanocobalamin decreased the expression of glucose utilizing genes by C. rodentium, a metabolic attribute previously associated with pathogen virulence. CONCLUSIONS: Oral vitamin B12 supplementation promoted C. rodentium colonization in mice by altering the activities of the Lachnospiraceae populations in the gut. A lower abundance of select Lachnospiraceae species correlated to higher p40 subunit levels, while the detection of Parasutterella exacerbated inflammatory markers in the colon of naïve mice. The B12-induced change in gut ecology enhanced the ability of C. rodentium colonization by impacting key microbe-host interactions that help with pathogen exclusion. This research provides insight into how B12 impacts the gut microbiota and highlights potential consequences of disrupting microbial B12 competition/sharing through over-supplementation. Video Abstract.

The role of HMGB1 in COVID-19-induced cytokine storm and its potential therapeutic targets: A review.

Hyperinflammation characterized by elevated proinflammatory cytokines known as 'cytokine storms' is the major cause of high severity and mortality seen in COVID-19 patients. The pathology behind the cytokine storms is currently unknown. Increased HMGB1 levels in serum/plasma of COVID-19 patients were reported by many studies, which positively correlated with the level of proinflammatory cytokines. Dead cells following SARS-CoV-2 infection might release a large amount of HMGB1 and RNA of SARS-CoV-2 into extracellular space. HMGB1 is a well-known inflammatory mediator. Additionally, extracellular HMGB1 might interact with SARS-CoV-2 RNA because of its high capability to bind with a wide variety of molecules including nucleic acids and could trigger massive proinflammatory immune responses. This review aimed to critically explore the many possible pathways by which HMGB1-SARS-CoV-2 RNA complexes mediate proinflammatory responses in COVID-19. The contribution of these pathways to impair host immune responses against SARS-CoV-2 infection leading to a cytokine storm was also evaluated. Moreover, since blocking the HMGB1-SARS-CoV-2 RNA interaction might have therapeutic value, some of the HMGB1 antagonists have been reviewed. The HMGB1- SARS-CoV-2 RNA complexes might trigger endocytosis via RAGE which is linked to lysosomal rupture, PRRs activation, and pyroptotic death. High levels of the proinflammatory cytokines produced might suppress many immune cells leading to uncontrolled viral infection and cell damage with more HMGB1 released. Altogether these mechanisms might initiate a proinflammatory cycle leading to a cytokine storm. HMGB1 antagonists could be considered to give benefit in alleviating cytokine storms and serve as a potential candidate for COVID-19 therapy.

Crohn's Disease, Host-Microbiota Interactions, and Immunonutrition: Dietary Strategies Targeting Gut Microbiome as Novel Therapeutic Approaches.

Crohn's disease (CD) is a complex, disabling, idiopathic, progressive, and destructive disorder with an unknown etiology. The pathogenesis of CD is multifactorial and involves the interplay between host genetics, and environmental factors, resulting in an aberrant immune response leading to intestinal inflammation. Due to the high morbidity and long-term management of CD, the development of non-pharmacological approaches to mitigate the severity of CD has recently attracted great attention. The gut microbiota has been recognized as an important player in the development of CD, and general alterations in the gut microbiome have been established in these patients. Thus, the gut microbiome has emerged as a pre-eminent target for potential new treatments in CD. Epidemiological and interventional studies have demonstrated that diet could impact the gut microbiome in terms of composition and functionality. However, how specific dietary strategies could modulate the gut microbiota composition and how this would impact host-microbe interactions in CD are still unclear. In this review, we discuss the most recent knowledge on host-microbe interactions and their involvement in CD pathogenesis and severity, and we highlight the most up-to-date information on gut microbiota modulation through nutritional strategies, focusing on the role of the microbiota in gut inflammation and immunity.

Multi-omics analyses of airway host-microbe interactions in chronic obstructive pulmonary disease identify potential therapeutic interventions.

The mechanistic role of the airway microbiome in chronic obstructive pulmonary disease (COPD) remains largely unexplored. We present a landscape of airway microbe-host interactions in COPD through an in-depth profiling of the sputum metagenome, metabolome, host transcriptome and proteome from 99 patients with COPD and 36 healthy individuals in China. Multi-omics data were integrated using sequential mediation analysis, to assess in silico associations of the microbiome with two primary COPD inflammatory endotypes, neutrophilic or eosinophilic inflammation, mediated through microbial metabolic interaction with host gene expression. Hypotheses of microbiome-metabolite-host interaction were identified by leveraging microbial genetic information and established metabolite-human gene pairs. A prominent hypothesis for neutrophil-predominant COPD was altered tryptophan metabolism in airway lactobacilli associated with reduced indole-3-acetic acid (IAA), which was in turn linked to perturbed host interleukin-22 signalling and epithelial cell apoptosis pathways. In vivo and in vitro studies showed that airway microbiome-derived IAA mitigates neutrophilic inflammation, apoptosis, emphysema and lung function decline, via macrophage-epithelial cell cross-talk mediated by interleukin-22. Intranasal inoculation of two airway lactobacilli restored IAA and recapitulated its protective effects in mice. These findings provide the rationale for therapeutically targeting microbe-host interaction in COPD.

Virus-Host Interactions and Genetic Diversity of Antarctic Sea Ice Bacteriophages.

Although we know the generally appreciated significant roles of microbes in sea ice and polar waters, detailed studies of virus-host systems from such environments have been so far limited by only a few available isolates. Here, we investigated infectivity under various conditions, infection cycles, and genetic diversity of the following Antarctic sea ice bacteriophages: Paraglaciecola Antarctic GD virus 1 (PANV1), Paraglaciecola Antarctic JLT virus 2 (PANV2), Octadecabacter Antarctic BD virus 1 (OANV1), and Octadecabacter Antarctic DB virus 2 (OANV2). The phages infect common sea ice bacteria belonging to the genera Paraglaciecola or Octadecabacter. Although the phages are marine and cold-active, replicating at 0°C to 5°C, they all survived temporal incubations at ≥30°C and remained infectious without any salts or supplemented only with magnesium, suggesting a robust virion assembly maintaining integrity under a wide range of conditions. Host recognition in the cold proved to be effective, and the release of progeny viruses occurred as a result of cell lysis. The analysis of viral genome sequences showed that nearly one-half of the gene products of each virus are unique, highlighting that sea ice harbors unexplored virus diversity. Based on predicted genes typical for tailed double-stranded DNA phages, we suggest placing the four studied viruses in the class Caudoviricetes. Searching against viral sequences from metagenomic assemblies, we revealed that related viruses are not restricted to Antarctica but are also found in distant marine environments. IMPORTANCE Very little is known about sea ice microbes despite the significant role played by sea ice in the global oceans as well as microbial input into biogeochemical cycling. Studies on the sea ice viruses have been typically limited to -omics-based approaches and microscopic examinations of sea ice samples. To date, only four cultivable viruses have been isolated from Antarctic sea ice. Our study of these unique isolates advances the understanding of the genetic diversity of viruses in sea ice environments, their interactions with host microbes, and possible links to other biomes. Such information contributes to more accurate future sea ice biogeochemical models.

The Age of Next-Generation Therapeutic-Microbe Discovery: Exploiting Microbe-Microbe and Host-Microbe Interactions for Disease Prevention.

Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses.

Host genetic and environmental factors including age, biological sex, diet, geographical location, microbiome composition and metabolites converge to influence innate and adaptive immune responses to vaccines. Failure to understand and account for these factors when investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy may impair the development of the next generation of vaccines. Most studies aimed at identifying mechanisms of vaccine-mediated immune protection have focused on adaptive immune responses. It is well established, however, that mobilization of the innate immune response is essential to the development of effective cellular and humoral immunity. A comprehensive understanding of the innate immune response and environmental factors that contribute to the development of broad and durable cellular and humoral immune responses to SARS-CoV-2 and other vaccines requires a holistic and unbiased approach. Along with optimization of the immunogen and vectors, the development of adjuvants based on our evolving understanding of how the innate immune system shapes vaccine responses will be essential. Defining the innate immune mechanisms underlying the establishment of long-lived plasma cells and memory T cells could lead to a universal vaccine for coronaviruses, a key biomedical priority.

Coral-microbe interactions: their importance to reef function and survival.

Many different microorganisms associate with the coral host in a single entity known as the holobiont, and their interactions with the host contribute to coral health, thereby making them a fundamental part of reef function, survival, and conservation. As corals continue to be susceptible to bleaching due to environmental stress, coral-associated bacteria may have a potential role in alleviating bleaching. This review provides a synthesis of the various roles bacteria have in coral physiology and development, and explores the possibility that changes in the microbiome with environmental stress could have major implications in how corals acclimatize and survive. Recent studies on the interactions between the coral's algal and bacterial symbionts elucidate how bacteria may stabilize algal health and, therefore, mitigate bleaching. A summary of the innovative tools and experiments to examine host-microbe interactions in other cnidarians (a temperate coral, a jellyfish, two anemones, and a freshwater hydroid) is offered in this review to delineate our current knowledge of mechanisms underlying microbial establishment and maintenance in the animal host. A better understanding of these mechanisms may enhance the success of maintaining probiotics long-term in corals as a conservation strategy.

Metabolic modeling of host-microbe interactions for therapeutics in colorectal cancer.

The onset of colorectal cancer (CRC) is often attributed to gut bacterial dysbiosis, and thus gut microbiota are highly relevant in devising treatment strategies. Certain gut microbes, like Enterococcus spp., exhibit remarkable anti-neoplastic and probiotic properties, which can aid in silver nanoparticle (AgNPs) induced reactive oxygen species (ROS)-based CRC treatment. However, the effects of AgNPs on gut microbial metabolism have not been reported thus far. In this study, a detailed systems-level understanding of ROS metabolism in Enterococcus durans (E. durans), a representative gut microbe, was gained using constraint-based modeling, wherein, the critical association between ROS and folate metabolism was established. Experimental studies involving low AgNP concentration treatment of E. durans cultures confirmed these modeling predictions (an increased extracellular folate concentration by 52%, at the 9th h of microbial growth, was observed). Besides, the computational studies established various metabolic pathways involving amino acids, energy metabolites, nucleotides, and SCFAs as the key players in elevating folate levels on ROS exposure. The anti-cancer potential of E. durans was also studied through MTT analysis of HCT 116 cells treated with microbial culture (AgNP treated) supernatant. A decrease in cell viability by 19% implicated the role of microbial metabolites (primarily folate) in causing cell death. The genome-scale modeling approach was then extended to extensively model CRC metabolism, as well as CRC-E. durans interactions in the context of CRC treatment, using tissue-specific metabolic models of CRC and healthy colon. These findings on further validation can facilitate the development of robust and effective cancer therapy.

Essential oil from Lavandula angustifolia elicits expression of three SbWRKY transcription factors and defense-related genes against sorghum damping-off.

Sorghum damping-off, caused by Fusarium solani (Mart.) Sacc., is a serious disease which causes economic loss in sorghum production. In this study, antagonistic activity of lavender essential oil (EO) at 0.5, 0.75, 1.0, 1.25, 1.5, and 1.6% against F. solani was studied in vitro. Their effects on regulation of three SbWRKY transcription factors, the response factor JERF3 and eight defense-related genes, which mediate different signaling pathways, in sorghum were investigated. Effects of application under greenhouse conditions were also evaluated. The results showed that lavender EO possesses potent antifungal activity against F. solani. A complete inhibition in the fungal growth was recorded for lavender EO at 1.6%. Gas chromatography-mass spectrometric analysis revealed that EO antifungal activity is most likely attributed to linalyl anthranilate, α-terpineol, eucalyptol, α-Pinene, and limonene. Observations using transmission electron microscopy revealed many abnormalities in the ultrastructures of the fungal mycelium as a response to treating with lavender EO, indicating that multi-mechanisms contributed to their antagonistic behavior. Results obtained from Real-time PCR investigations demonstrated that the genes studied were overexpressed, to varying extents in response to lavender EO. However, SbWRKY1 was the highest differentially expressed gene followed by JERF3, which suggest they play primary role(s) in synchronously organizing the transcription-regulatory-networks enhancing the plant resistance. Under greenhouse conditions, treating of sorghum grains with lavender EO at 1.5% prior to infection significantly reduced disease severity. Moreover, the growth parameters evaluated, the activities of antioxidant enzymes, and total phenolic and flavonoid contents were all enhanced. In contrast, lipid peroxidation was highly reduced. Results obtained from this study support the possibility of using lavender EO for control of sorghum damping-off. However, field evaluation is highly needed prior to any usage recommendation.

Exploring tea (Camellia sinensis) microbiome: Insights into the functional characteristics and their impact on tea growth promotion.

Tea (Camellia sinensis) is perhaps the most popular and economic beverage in the globe due to its distinctive fragrance and flavour generated by the leaves of commercially farmed tea plants. The tea microbiome has now become a prominent topic of attention for microbiologists in recent years as it can help the plant for soil nutrient acquisition as well as stress management. Tea roots are well known to be colonized by Arbuscular Mycorrhizal Fungi (AMF) and many other beneficial microorganisms that boost the growth of the tea which increases leaf amino acids, protein, caffeine, and polyphenols content. One of the primary goals of rhizosphere microbial biology is to aid in the establishment of agricultural systems that provide high quantities of the food supply while minimizing environmental effects and anthropogenic activities. The present review is aimed to highlight the importance of microbes (along with their phylogeny) derived from cultivated and natural tea rhizospheres to understand the role of AMF and rhizospheric bacterial population to improve plant growth, enhancement of tea quality, and protecting tea plants from pathogens. This review also summarizes recent advances in our understanding of the diversity and profile of tea-associated bacteria. The utilization of the tea microbiome as a "natural resource" could provide holistic development in tea cultivation to ensure sustainability, highlighting knowledge gaps and future microbiome research.

Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis.

The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. IMPORTANCE Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics-based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.

Plant growth-promoting activities of bacterial endophytes isolated from the medicinal plant Pairs polyphylla var. yunnanensis.

Pairs polyphylla var. yunnanensis (Paris L.) is a valuable medicinal plant used in traditional Chinese medicine. The market demand for P. polyphylla has increased over time, but it has slow growth and a low natural propagation rate. Endophytic bacteria are bioactive microorganisms that form a mutualistic relationship with host plants in long-term coordinated evolution, and they can promote the growth and accumulation of effective components in host plants. The aims of this study were to identify endophytic bacteria of P. polyphylla and to characterize their properties in promoting plant growth. A total of 10 endophytic bacteria were isolated from rhizomes of P. polyphylla. The isolated endophytes exhibited a variable capacity for indole acetic acid production, phosphate solubilization and nitrogen fixation. To investigate the effects of the endophytes on plant growth, four endophyte strains, G5, J2, G20, and Y2, were selected to compare their ability to promote plant growth. The results indicated that microbial endophytes isolated from P. polyphylla rhizomes play a vital role in improving P. polyphylla plant growth and could be used as inoculants to establish a sustainable crop production system.