Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.

Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gaps in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN.

Amelioration of the physio-biochemical responses to salinity stress and computing the primary germination index components in cauliflower on seed priming.

The significant horticultural crop, cauliflower (Brassica oleracea L. var. botrytis) is vulnerable to the excessive salt concentration in the soil, which contributes to its scaled-down growth and productivity, among other indices. The current study examines the efficacy of hydropriming, halopriming, and osmopriming on the physio-biochemical attributes and tolerance to salinity (100 mM NaCl) in cauliflower under controlled conditions. The results showed that the salinity (100 mM NaCl) has significant deleterious impacts on cauliflower seed germination, seedling growth, and photosynthetic attributes, and provoked the production of reactive oxygen species. In contrast, different priming approaches proved beneficial in mitigating the negative effects of salinity and boosted the germination, vigor indices, seedling growth, and physio-biochemical attributes like photosynthetic pigments, protein, and proline content while suppressing oxidative damage and MDA content in cauliflower seedlings in treatment- and dose-dependent manner. PCA revealed 61% (PC1) and 15% (PC2) of the total variance with substantial positive relationships and high loading conditions on all germination attributes on PC1 with greater PC1 scores for PEG treatments showing the increased germination indices in PEG-treated seeds among all the priming treatments tested. All 13 distinct priming treatments tried clustered into three groups as per Ward's approach of systematic categorization, clustering the third group showing relatively poor germination performances. Most germination traits exhibited statistically significant associations at the p < 0.01 level. Overall, the results established the usefulness of the different priming approaches facilitating better germination, survival, and resistance against salinity in the cauliflower to be used further before sowing in the salt-affected agro-ecosystems.

Plasma metabolites with mechanistic and clinical links to the neurovascular disease cavernous angioma.

BACKGROUND: Cavernous angiomas (CAs) affect 0.5% of the population, predisposing to serious neurologic sequelae from brain bleeding. A leaky gut epithelium associated with a permissive gut microbiome, was identified in patients who develop CAs, favoring lipid polysaccharide producing bacterial species. Micro-ribonucleic acids along with plasma levels of proteins reflecting angiogenesis and inflammation were also previously correlated with CA and CA with symptomatic hemorrhage. METHODS: The plasma metabolome of CA patients and CA patients with symptomatic hemorrhage was assessed using liquid-chromatography mass spectrometry. Differential metabolites were identified using partial least squares-discriminant analysis (p < 0.05, FDR corrected). Interactions between these metabolites and the previously established CA transcriptome, microbiome, and differential proteins were queried for mechanistic relevance. Differential metabolites in CA patients with symptomatic hemorrhage were then validated in an independent, propensity matched cohort. A machine learning-implemented, Bayesian approach was used to integrate proteins, micro-RNAs and metabolites to develop a diagnostic model for CA patients with symptomatic hemorrhage. RESULTS: Here we identify plasma metabolites, including cholic acid and hypoxanthine distinguishing CA patients, while arachidonic and linoleic acids distinguish those with symptomatic hemorrhage. Plasma metabolites are linked to the permissive microbiome genes, and to previously implicated disease mechanisms. The metabolites distinguishing CA with symptomatic hemorrhage are validated in an independent propensity-matched cohort, and their integration, along with levels of circulating miRNAs, enhance the performance of plasma protein biomarkers (up to 85% sensitivity and 80% specificity). CONCLUSIONS: Plasma metabolites reflect CAs and their hemorrhagic activity. A model of their multiomic integration is applicable to other pathologies.

Cavernous angiomas (CAs) are clusters of abnormal blood vessels found in the brain or spinal cord. A blood test that could identify people with CAs that have recently bled would help determine who need surgery or closer medical monitoring. We looked at the blood of people with CAs to compare the levels of metabolites, a type of small molecule produced within the body, in those who had recently bled and those who had not. We found that some metabolites may contribute to CA and have an impact on CA symptoms. Monitoring the levels of these metabolites can determine whether there had been a recent bleed. In the future, drugs or other therapies could be developed that would block or change the levels of these molecules and possibly be used to treat CA disease.

Microbiome response in an urban river system is dominated by seasonality over wastewater treatment upgrades.

BACKGROUND: Microorganisms such as coliform-forming bacteria are commonly used to assess freshwater quality for drinking and recreational use. However, such organisms do not exist in isolation; they exist within the context of dynamic, interactive microbial communities which vary through space and time. Elucidating spatiotemporal microbial dynamics is imperative for discriminating robust community changes from ephemeral ecological trends, and for improving our overall understanding of the relationship between microbial communities and ecosystem health. We conducted a seven-year (2013-2019) microbial time-series investigation in the Chicago Area Waterways (CAWS): an urban river system which, in 2016, experienced substantial upgrades to disinfection processes at two wastewater reclamation plants (WRPs) that discharge into the CAWS and improved stormwater capture, to improve river water quality and reduce flooding. Using culture-independent and culture-dependent approaches, we compared CAWS microbial ecology before and after the intervention. RESULTS: Examinations of time-resolved beta distances between WRP-adjacent sites showed that community similarity measures were often consistent with the spatial orientation of site locations to one another and to the WRP outfalls. Fecal coliform results suggested that upgrades reduced coliform-associated bacteria in the effluent and the downstream river community. However, examinations of whole community changes through time suggest that the upgrades did little to affect overall riverine community dynamics, which instead were overwhelmingly driven by yearly patterns consistent with seasonality. CONCLUSIONS: This study presents a systematic effort to combine 16S rRNA gene amplicon sequencing with traditional culture-based methods to evaluate the influence of treatment innovations and systems upgrades on the microbiome of the Chicago Area Waterway System, representing the longest and most comprehensive characterization of the microbiome of an urban waterway yet attempted. We found that the systems upgrades were successful in improving specific water quality measures immediately downstream of wastewater outflows. Additionally, we found that the implementation of the water quality improvement measures to the river system did not disrupt the overall dynamics of the downstream microbial community, which remained heavily influenced by seasonal trends. Such results emphasize the dynamic nature of microbiomes in open environmental systems such as the CAWS, but also suggest that the seasonal oscillations remain consistent even when perturbed.

Impacts of COVID-19 on Glycemia and Risk of Diabetic Ketoacidosis.

Reports indicate that coronavirus disease 2019 (COVID-19) may impact pancreatic function and increase type 2 diabetes (T2D) risk, although real-world COVID-19 impacts on HbA1c and T2D are unknown. We tested whether COVID-19 increased HbA1c, risk of T2D, or diabetic ketoacidosis (DKA). We compared pre- and post-COVID-19 HbA1c and T2D risk in a large real-world clinical cohort of 8,755 COVID-19(+) patients and 11,998 COVID-19(-) matched control subjects. We investigated whether DKA risk was modified in COVID-19(+) patients with type 1 diabetes (T1D) (N = 701) or T2D (N = 21,830), or by race and sex. We observed a statistically significant, albeit clinically insignificant, HbA1c increase post-COVID-19 (all patients ΔHbA1c = 0.06%; with T2D ΔHbA1c = 0.1%) and no increase among COVID-19(-) patients. COVID-19(+) patients were 40% more likely to be diagnosed with T2D compared with COVID-19(-) patients and 28% more likely for the same HbA1c change as COVID-19(-) patients, indicating that COVID-19-attributed T2D risk may be due to increased recognition during COVID-19 management. DKA in COVID-19(+) patients with T1D was not increased. COVID-19(+) Black patients with T2D displayed disproportionately increased DKA risk (hazard ratio 2.46 [95% CI 1.48-6.09], P = 0.004) compared with White patients, suggesting a need for further clinical awareness and investigation.

A Multimodal Approach to Discover Biomarkers for Taxane-Induced Peripheral Neuropathy (TIPN): A Study Protocol.

Introduction: Taxanes are a class of chemotherapeutics commonly used to treat various solid tumors, including breast and ovarian cancers. Taxane-induced peripheral neuropathy (TIPN) occurs in up to 70% of patients, impacting quality of life both during and after treatment. TIPN typically manifests as tingling and numbness in the hands and feet and can cause irreversible loss of function of peripheral nerves. TIPN can be dose-limiting, potentially impacting clinical outcomes. The mechanisms underlying TIPN are poorly understood. As such, there are limited treatment options and no tools to provide early detection of those who will develop TIPN. Although some patients may have a genetic predisposition, genetic biomarkers have been inconsistent in predicting chemotherapy-induced peripheral neuropathy (CIPN). Moreover, other molecular markers (eg, metabolites, mRNA, miRNA, proteins) may be informative for predicting CIPN, but remain largely unexplored. We anticipate that combinations of multiple biomarkers will be required to consistently predict those who will develop TIPN. Methods: To address this clinical gap of identifying patients at risk of TIPN, we initiated the Genetics and Inflammatory Markers for CIPN (GENIE) study. This longitudinal multicenter observational study uses a novel, multimodal approach to evaluate genomic variation, metabolites, DNA methylation, gene expression, and circulating cytokines/chemokines prior to, during, and after taxane treatment in 400 patients with breast cancer. Molecular and patient reported data will be collected prior to, during, and after taxane therapy. Multi-modal data will be used to develop a set of comprehensive predictive biomarker signatures of TIPN. Conclusion: The goal of this study is to enable early detection of patients at risk of developing TIPN, provide a tool to modify taxane treatment to minimize morbidity from TIPN, and improved patient quality of life. Here we provide a brief review of the current state of research into CIPN and TIPN and introduce the GENIE study design.

Gestational Insulin Resistance Is Mediated by the Gut Microbiome-Indoleamine 2,3-Dioxygenase Axis.

BACKGROUND & AIMS: Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction. METHODS: The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM was studied with the use of fecal microbial transplants (FMTs). RESULTS: Significant variation in GM alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time point specific, with the species enriched at gestation day 15/19 (G15/19), a point of heightened IR, being distinct from those enriched before or after pregnancy. Metabolomics revealed elevated plasma kynurenine at G15/19 in all 3 mouse strains. IDO1, the rate-limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine level effects on IR derive from the GM in both mouse and human pregnancy. CONCLUSIONS: GM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation, and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1. (Gestational Gut Microbiome-IDO1 Axis Mediates Pregnancy Insulin Resistance; EMBL-ENA ID: PRJEB45047. MetaboLights ID: MTBLS3598).

Suppression of local type I interferon by gut microbiota-derived butyrate impairs antitumor effects of ionizing radiation.

The antitumor effects of ionizing radiation (IR) are mediated in part through activation of innate and adaptive immunity. Here we report that gut microbiota influences tumor control following IR. Vancomycin decreased the abundance of butyrate-producing gut bacteria and enhanced antitumor responses to IR. Oral administration of Lachnospiraceae, a family of vancomycin-sensitive bacteria, was associated with increased systemic and intratumoral butyric acid levels and impaired the efficacy of IR in germ-free (GF) mice. Local butyrate inhibited STING-activated type I IFN expression in dendritic cells (DCs) through blockade of TBK1 and IRF3 phosphorylation, which abrogated IR-induced tumor-specific cytotoxic T cell immune responses without directly protecting tumor cells from radiation. Our findings demonstrate that the selective targeting of butyrate-producing microbiota may provide a novel therapeutic option to enhance tumor radiation sensitivity.

Draft Genome Sequence of Pseudarthrobacter sp. Strain ATCC 49442 (Formerly Micrococcus luteus), a Pyridine-Degrading Bacterium.

We present here the draft genome sequence of a pyridine-degrading bacterium, Micrococcus luteus ATCC 49442, which was reclassified as Pseudarthrobacter sp. strain ATCC 49442 based on its draft genome sequence. Its genome length is 4.98 Mbp, with 64.81% GC content.

COVID-19: Assessment of knowledge and awareness in Indian society.

COVID-19, which was initiated regionally at Wuhan of China, has become a global pandemic by infecting people of almost all the world. Human civilizations are facing threat for their survival and livelihood. No country are getting any substantial relief and solution from this pandemic rather to convince their citizens to make aware and taking precaution by changing their living style. In view of this, this study attempted to assess the awareness, threat, symptoms and its prevention among people of India about the COVID-19. A total of 522 responses from all over India were received. The respondents have adequate awareness for COVID-19 outbreak and its preventive measures, out of total, 98% (513) answered that the virus spreads from one person to another, 95% (494) answered that the disease is caused by a virus. Peoples understand the importance of social distancing and other preventive measures prescribed by the government with good attitude for coronavirus. Peoples are following trusted sources for corona information, having confidence to defeat disease but showed their concern for corona threat, are aware about the virus, its common symptoms and prevention, govt. testing and medical facilities. Principal component analysis was used to identify the latent dimensions regarding people's preventive measures and was found that they are majorly adopting three methods, that is, lockdown, naturopathy and social distancing. This study will help government and peoples to understand and handle this coronavirus pandemic effectively and in prevention of COVID-19, which is crucial for the awareness of society in coming time.

Draft Genome Sequence of 2-Methylpyridine-, 2-Ethylpyridine-, and 2-Hydroxypyridine-Degrading Arthrobacter sp. Strain ATCC 49987.

Here, we report the draft genome sequence of Arthrobacter sp. strain ATCC 49987, consisting of three contigs with a total length of 4.4 Mbp. Based on the genome sequence, we suggest reclassification of Arthrobacter sp. strain ATCC 49987 as Pseudarthrobacter sp. strain ATCC 49987.

Correlation between weather and COVID-19 pandemic in India: An empirical investigation.

This study is an attempt to find and analyze the correlation between Covid-19 pandemic and weather conditions in Indian context. Secondary data analysis of surveillance data of COVID-19 is taken from Wikipedia (updating information from World Health Organization) & statista.com and weather data through Power Data Access Viewer (DAV) (power.Iarc.nasa.gov) from NASA after mentioning latitude and longitude of India. The minimum temperature (°C) at 2 metre, maximum temperature (°C) at 2 metre, temperature (°C) at 2 metre and relative humidity (%) are taken as component of weather. To find the association, Spearman's rank correlation test was applied. The minimum, maximum temperature (°C) at 2 m, temperatures (°C) at 2 m and humidity at 2 m are significantly correlated with COVID-19 pandemic cases (r = 0.93, 0.94, 0.83, and 0.30) at 99% two-tailed significance level. The findings serve as an initial evidence to reduce the incidence rate of COVID-19 in India and useful in policy making.

The early gut microbiome could protect against severe retinopathy of prematurity.

In this study, 6 infants with type 1 retinopathy of prematurity (ROP) were compared with 4 high-risk preterm neonates without any ROP but similar baseline neonatal comorbidities. The infants with type-1 ROP showed significant enrichment of Enterobacteriaceae at 28 weeks' postmenstrual age. Several metabolic pathways, including several amino acid metabolism pathways, were enriched in gut microbiota of infants without ROP. Based on these findings, we posit a possible association between early gut microbiome profile and ROP pathogenesis. Furthermore, it is possible that absence of Enterobacteriaceae overabundance, in addition to enrichment of amino acid biosynthesis pathways, may protect against severe ROP in high-risk preterm infants.

Permissive microbiome characterizes human subjects with a neurovascular disease cavernous angioma.

Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We here assess microbiome differences in a larger cohort of human subjects with and without CA, and among subjects with different clinical features, and conduct more definitive microbial analyses using metagenomic shotgun sequencing. Relative abundance of distinct bacterial species in CA patients is shown, consistent with postulated permissive microbiome driving CA lesion genesis via lipopolysaccharide signaling, in humans as in mice. Other microbiome differences are related to CA clinical behavior. Weighted combinations of microbiome signatures and plasma inflammatory biomarkers enhance associations with disease severity and hemorrhage. This is the first demonstration of a sensitive and specific diagnostic microbiome in a human neurovascular disease.

Microbiome profile associated with malignant pleural effusion.

INTRODUCTION: There is ongoing research into the development of novel molecular markers that may complement fluid cytology malignant pleural effusion (MPE) diagnosis. In this exploratory pilot study, we hypothesized that there are distinct differences in the pleural fluid microbiome profile of malignant and non-malignant pleural diseases. METHOD: From a prospectively enrolled pleural fluid biorepository, samples of MPE were included. Non-MPE effusion were included as comparators. 16S rRNA gene V4 region amplicon sequencing was performed. Exact Sequence Variants (ESVs) were used for diversity analyses. The Shannon and Richness indices of alpha diversity and UniFrac beta diversity measures were tested for significance using permutational multivariate analysis of variance. Analyses of Composition of Microbiome was used to identify differentially abundant bacterial ESVs between the groups controlled for multiple hypothesis testing. RESULTS: 38 patients with MPE and 9 with non-MPE were included. A subgroup of patients with metastatic adenocarcinoma histology were identified among MPE group (adenocarcinoma of lung origin (LA-MPE) = 11, breast origin (BA-MPE) = 11). MPE presented with significantly greater alpha diversity compared to non-MPE group. Within the MPE group, BA-MPE was more diverse compared to LA-MPE group. In multivariable analysis, ESVs belonging to family S24-7 and genera Allobaculum, Stenotrophomonas, and Epulopiscium were significantly enriched in the malignant group compared to the non-malignant group. CONCLUSION: Our results are the first to demonstrate a microbiome signature according to MPE and non-MPE. The role of microbiome in pleural effusion pathogenesis needs further exploration.

The Future of Microbiome-Based Therapeutics in Clinical Applications.

The microbiome, a collection of microorganisms, their genomes, and the surrounding environmental conditions, is akin to a human organ, and knowledge is emerging on its role in human health and diseases. The influence of the microbiome in drug response has only been investigated in detail for the last 10 years. The human microbiome is a complex and highly dynamic system, which varies dramatically between individuals, yet there exists a common core microbiome that is heritable and can be transmitted to progeny. Here, we review the role of the human microbiome, which is now widely accepted as a major factor that drives the interpersonal variation in therapeutic response. We describe examples in which the microbiome modifies drug action. Despite its complexity, the microbiome can be readily altered, with the potential to increase the benefits and reduce the toxicity and side effects associated with pharmaceutical drugs. The potential of new microbiome-based strategies, such as fecal microbiota transplant, probiotics, and phage therapy, as promising medical therapeutics are outlined. We also suggest a combination reductionist and system-level approaches that could be applied to further investigate the role of microbiota in drug metabolism modulation of drug response. Finally, we emphasize the importance of combining microbiome and pharmacology studies as a novel means to treat disease and reduce side effects.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1ß positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.

Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts.

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum ß-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota.IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.

Associations between fungal and bacterial microbiota of airways and asthma endotypes.

BACKGROUND: The relationship between asthma, atopy, and underlying type 2 (T2) airway inflammation is complex. Although the bacterial airway microbiota is known to differ in asthmatic patients, the fungal and bacterial markers that discriminate T2-high (eosinophilic) and T2-low (neutrophilic/mixed-inflammation) asthma and atopy are still incompletely identified. OBJECTIVES: The aim of this study was to demonstrate the fungal microbiota structure of airways in asthmatic patients associated with T2 inflammation, atopy, and key clinical parameters. METHODS: We collected endobronchial brush (EB) and bronchoalveolar lavage (BAL) samples from 39 asthmatic patients and 19 healthy subjects followed by 16S gene and internal transcribed spacer-based microbiota sequencing. The microbial sequences were classified into exact sequence variants. The T2 phenotype was defined by using a blood eosinophil count with a threshold of 300 cells/µL. RESULTS: Fungal diversity was significantly lower in EB samples from patients with T2-high compared with T2-low inflammation; key fungal genera enriched in patients with T2-high inflammation included Trichoderma species, whereas Penicillium species was enriched in patients with atopy. In BAL fluid samples the dominant genera were Cladosporium, Fusarium, Aspergillus, and Alternaria. Using generalized linear models, we identified significant associations between specific fungal exact sequence variants and FEV1, fraction of exhaled nitric oxide values, BAL fluid cell counts, and corticosteroid use. Investigation of interkingdom (bacterial-fungal) co-occurrence patterns revealed different topologies between asthmatic patients and healthy control subjects. Random forest models with fungal classifiers predicted asthma status with 75% accuracy for BAL fluid samples and 80% accuracy for EB samples. CONCLUSIONS: We demonstrate clear differences in bacterial and fungal microbiota in asthma-associated phenotypes. Our study provides additional support for considering microbial signatures in delineating asthma phenotypes.

Draft Genome Sequence of Rhodococcus sp. Strain ATCC 49988, a Quinoline-Degrading Bacterium.

We report here the 4.9-Mb genome sequence of a quinoline-degrading bacterium, Rhodococcus sp. strain ATCC 49988. The draft genome data will enable the identification of genes and future genetic modification to enhance traits relevant to heteroaromatic compound degradation.