Epithelial Na+ Channel Activation after Bile Duct Ligation with Mineralocorticoid Receptor Blockade.

BACKGROUND: Sodium and fluid retention in liver disease are classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). However, evidence of fluid retention in patients without RAAS activation suggests the involvement of additional mechanisms. In vitro, bile acids activate the epithelial Na+ channel (ENaC) found in the aldosterone-sensitive distal nephron. If this occurs in vivo, ENaC may become activated in liver disease even with antagonism of aldosterone signaling. METHODS: To test this, we performed bile duct ligation to induce liver disease and increase circulating bile acids in mice given spironolactone to antagonize aldosterone signaling. We analyzed effects on blood, urine and body composition. We also determined the effects of taurocholic acid, a primary conjugated bile acid elevated in liver disease, on ion fluxes in microperfused rabbit collecting ducts. RESULTS: Bile duct ligation increased benzamil-sensitive natriuresis compared to sham, indicating ENaC activation. These effects were not explained by effects on ENaC expression, cleavage, or localization. Bile duct ligated mice also gained significantly more fluid than sham-operated animals. Blocking ENaC reversed fluid gains in bile duct ligated mice but had no effect in shams. In dissected collecting ducts from rabbits, which express ENaC, taurocholic acid stimulated net Na+ absorption. CONCLUSIONS: Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease.

Euglycemic Diabetic Ketoacidosis Induced by Sodium-Glucose Cotransporter-2 Inhibitor Use and Coronary Angiography: A Case Report.

Euglycemic diabetic ketoacidosis (EDKA) is an uncommon subtype of diabetic ketoacidosis (DKA) which presents with similar laboratory findings to classic DKA with the exception of blood glucose levels being under 250 mg/dl. EDKA has several etiologies including pregnancy, starvation and the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2). SGLT-2 inhibitors such as empagliflozin and dapagliflozin are increasing in popularity due to their positive benefits for patients with diabetes mellitus and cardiac disease. EDKA is underdiagnosed as it presents with blood sugar levels lower than expected in classic DKA. This case report describes a well-controlled type 2 diabetic patient prescribed an SGLT-2 inhibitor who developed EDKA after undergoing coronary angiography for acute heart failure.

Multi-Omics Profiling of Candida albicans Grown on Solid Versus Liquid Media.

Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.

Functional alterations and predictive capacity of gut microbiome in type 2 diabetes.

The gut microbiome plays a significant role in the development of Type 2 Diabetes Mellitus (T2DM), but the functional mechanisms behind this association merit deeper investigation. Here, we used the nanopore sequencing technology for metagenomic analyses to compare the gut microbiome of individuals with T2DM from the United Arab Emirates (n = 40) with that of control (n = 44). DMM enterotyping of the cohort resulted concordantly with previous results, in three dominant groups Bacteroides (K1), Firmicutes (K2), and Prevotella (K3) lineages. The diversity analysis revealed a high level of diversity in the Firmicutes group (K2) both in terms of species richness and evenness (Wilcoxon rank-sum test, p value < 0.05 vs. K1 and K3 groups), consistent with the Ruminococcus enterotype described in Western populations. Additionally, functional enrichment analyses of KEGG modules showed significant differences in abundance between individuals with T2DM and controls (FDR < 0.05). These differences include modules associated with the degradation of amino acids, such as arginine, the degradation of urea as well as those associated with homoacetogenesis. Prediction analysis with the Predomics approach suggested potential biomarkers for T2DM, including a balance between a depletion of Enterococcus faecium and Blautia lineages with an enrichment of Absiella spp or Eubacterium limosum in T2DM individuals, highlighting the potential of metagenomic analysis in predicting predisposition to diabetic cardiomyopathy in T2DM patients.

Transforming medical device biofilm control with surface treatment using microfabrication techniques.

Biofilm deposition on indwelling medical devices and implanted biomaterials is frequently attributed to the prevalence of resistant infections in humans. Further, the nature of persistent infections is widely believed to have a biofilm etiology. In this study, the wettability of commercially available indwelling medical devices was explored for the first time, and its effect on the formation of biofilm was determined in vitro. Surprisingly, all tested indwelling devices were found to be hydrophilic, with surface water contact angles ranging from 60° to 75°. First, we established a thriving Candida albicans biofilm growth at 24 hours. in YEPD at 30°C and 37°C plus serum in vitro at Cyclic olefin copolymer (COC) modified surface, which was subsequently confirmed via scanning electron microscopy, while their cellular metabolic function was assessed using the XTT cell viability assay. Surfaces with patterned wettability show that a contact angle of 110° (hydrophobic) inhibits C. albicans planktonic and biofilm formation completely compared to robust growth at a contact angle of 40° (hydrophilic). This finding may provide a novel antimicrobial strategy to prevent biofilm growth and antimicrobial resistance on indwelling devices and prosthetic implants. Overall, this study provides valuable insights into the surface characteristics of medical devices and their potential impact on biofilm formation, leading to the development of improved approaches to control and prevent microbial biofilms and re-infections.

Mineralocorticoid receptor-independent activation of ENaC in bile duct ligated mice.

Sodium and fluid retention in liver disease is classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). Aldosterone dives Na+ retention by activating the mineralocorticoid receptor and promoting the maturation and apical surface expression of the epithelial Na+ channel (ENaC), found in the aldosterone-sensitive distal nephron. However, evidence of fluid retention without RAAS activation suggests the involvement of additional mechanisms. Liver disease can greatly increase plasma and urinary bile acid concentrations and have been shown to activate ENaC in vitro. We hypothesize that elevated bile acids in liver disease activate ENaC and drive fluid retention independent of RAAS. We therefore increased circulating bile acids in mice through bile duct ligation (BDL) and measured effects on urine and body composition, while using spironolactone to antagonize the mineralocorticoid receptor. We found BDL lowered blood [K+] and hematocrit, and increased benzamil-sensitive natriuresis compared to sham, consistent with ENaC activation. BDL mice also gained significantly more body water. Blocking ENaC reversed fluid gains in BDL mice but had no effect in shams. In isolated collecting ducts from rabbits, taurocholic acid stimulated net Na+ absorption but had no effect on K+ secretion or flow-dependent ion fluxes. Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease which may provide additional therapeutic options for liver disease patients.

Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis.

Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.

Managing Energy Consumption of Devices with Multiconnectivity by Deep Learning and Software-Defined Networking.

Multiconnectivity allows user equipment/devices to connect to multiple radio access technologies simultaneously, including 5G, 4G (LTE), and WiFi. It is a necessity in meeting the increasing demand for mobile network services for the 5G and beyond wireless networks, while ensuring that mobile operators can still reap the benefits of their present investments. Multipath TCP (MPTCP) has been introduced to allow uninterrupted reliable data transmission over multiconnectivity links. However, energy consumption is a significant issue for multihomed wireless devices since most of them are battery-powered. This paper employs software-defined networking (SDN) and deep neural networks (DNNs) to manage the energy consumption of devices with multiconnectivity running MPTCP. The proposed method involves two lightweight algorithms implemented on an SDN controller, using a real hardware testbed of dual-homed wireless nodes connected to WiFi and cellular networks. The first algorithm determines whether a node should connect to a specific network or both networks. The second algorithm improves the selection made by the first by using a DNN trained on different scenarios, such as various network sizes and MPTCP congestion control algorithms. The results of our extensive experimentation show that this approach effectively reduces energy consumption while providing better network throughput performance compared to using single-path TCP or MPTCP Cubic or BALIA for all nodes.

Corrigendum: Altered composition of the oral microbiota in depression among cigarette smokers: A pilot study.

[This corrects the article DOI: 10.3389/fpsyt.2022.902433.].

Influence of glycoprotein MUC1 on trafficking of the Ca2+-selective ion channels, TRPV5 and TRPV6, and on in vivo calcium homeostasis.

Polymorphism of the gene encoding mucin 1 (MUC1) is associated with skeletal and dental phenotypes in human genomic studies. Animals lacking MUC1 exhibit mild reduction in bone density. These phenotypes could be a consequence of modulation of bodily Ca homeostasis by MUC1, as suggested by the previous observation that MUC1 enhances cell surface expression of the Ca2+-selective channel, TRPV5, in cultured unpolarized cells. Using biotinylation of cell surface proteins, we asked whether MUC1 influences endocytosis of TRPV5 and another Ca2+-selective TRP channel, TRPV6, in cultured polarized epithelial cells. Our results indicate that MUC1 reduces endocytosis of both channels, enhancing cell surface expression. Further, we found that mice lacking MUC1 lose apical localization of TRPV5 and TRPV6 in the renal tubular and duodenal epithelium. Females, but not males, lacking MUC1 exhibit reduced blood Ca2+. However, mice lacking MUC1 exhibited no differences in basal urinary Ca excretion or Ca retention in response to PTH receptor signaling, suggesting compensation by transport mechanisms independent of TRPV5 and TRPV6. Finally, humans with autosomal dominant tubulointerstitial kidney disease due to frame-shift mutation of MUC1 (ADTKD-MUC1) exhibit reduced plasma Ca concentrations compared to control individuals with mutations in the gene encoding uromodulin (ADTKD-UMOD), consistent with MUC1 haploinsufficiency causing reduced bodily Ca2+. In summary, our results provide further insight into the role of MUC1 in Ca2+-selective TRP channel endocytosis and the overall effects on Ca concentrations.

Suppression of NRF2 Activity by HIF-1α Promotes Fibrosis after Ischemic Acute Kidney Injury.

Acute kidney injury (AKI) is a rapid decline in renal function and can occur after ischemia/reperfusion injury (IRI) to the tubular epithelia. The nuclear factor erythroid-2-related factor 2 (NRF2) pathway protects against AKI and AKI-to-chronic kidney disease (CKD) progression, but we previously demonstrated that severe IRI maladaptively reduced NRF2 activity in mice. To understand the mechanism of this response, we subjected C57BL/6J mice to unilateral kidney IRI with ischemia times that were titrated to induce mild to severe injury. Mild IRI increased NRF2 activity and was associated with renal recovery, whereas severe IRI decreased NRF2 activity and led to progressive CKD. Due to these effects of ischemia, we tested the hypothesis that hypoxia-inducible factor-1α (HIF-1α) mediates NRF2 activity. To mimic mild and severe ischemia, we activated HIF-1α in HK-2 cells in nutrient-replete or nutrient-deficient conditions. HIF-1α activation in nutrient-replete conditions enhanced NRF2 nuclear localization and activity. However, in nutrient-deficient conditions, HIF-1α activation suppressed NRF2 nuclear localization and activity. Nuclear localization was rescued with HIF-1α siRNA knockdown. Our results suggest that severe ischemic AKI leads to HIF-1α-mediated suppression of NRF2, leading to AKI-to-CKD progression.

Analysis of SARS-CoV-2 viral loads in stool samples and nasopharyngeal swabs from COVID-19 patients in the United Arab Emirates.

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information was collected by standardized questionnaire and from the medical records of the patient. Of the 211 participants, 25% tested negative in both sample types at the time of this study and 53% of the remaining patients had detectable viral RNA in their stools. A positive fecal viral test was associated with male gender, diarrhea as a symptom, and hospitalization during infection. A positive correlation was also observed between a delayed onset of symptoms and a positive stool test. Viral load in stools positively correlated with, being overweight, exercising, taking antibiotics in the last 3 months and blood type O. The viral load in nasopharyngeal swabs, on the other hand, was higher for blood type A, and rhesus positive (Rh factor). Regression analysis showed no correlation between the viral loads measured in stool and nasopharyngeal samples in any given patient. The results of this work highlight the factors associated with a higher viral count in each sample. It also shows the importance of stool sample analysis for the follow-up and diagnosis of recovering COVID-19 patients.

Altered Composition of the Oral Microbiota in Depression Among Cigarette Smokers: A Pilot Study.

Alterations in the oral microbiota composition may influence mental health. However, linkages between compositional changes in the oral microbiota and their role in mental health among cigarette smokers remain largely unknown. In this study, we used shotgun metagenomics data for the oral microbiome of 105 participants. The data showed Bacteroidota, Fusobacteriota, Firmicutes, Proteobacteria, and Actinobacteria to be the most abundant phyla; Streptococcus, Haemophilus D, and Veillonella are the most abundant genera. Then, we clustered our subjects into avoidance and activation groups based on the behavioral activation for depression scale (BADS). Interestingly, the avoidance group exhibited a higher oral microbiome richness and diversity (alpha diversity). Differential abundance testing between BADS avoidance and activation groups showed the phyla Bacteroidota (effect size 0.5047, q = 0.0037), Campylobacterota (effect size 0.4012, q = 0.0276), Firmicutes A (effect size 0.3646, q = 0.0128), Firmicutes I (effect size 0.3581, q = 0.0268), and Fusobacteriota (effect size 0.6055, q = 0.0018) to be significantly increased in the avoidance group, but Verrucomicrobiota (effect size-0.6544, q = 0.0401), was found to be significantly decreased in the avoidance risk group. Network analysis of the 50 genera displaying the highest variation between both groups identified Campylobacter B, Centipeda, and Veillonella as hub nodes in the avoidance group. In contrast, Haemophilus and Streptococcus were identified as hub nodes in the activation group. Next, we investigated functional profiles of the oral microbiota based on BADS avoidance and activation groups and found Lysine degradations pathway was significantly enriched between both groups (ANCOM-BC, q = 0.0692). Altogether, we provide evidence for the presence of depression-related changes in the oral microbiota of smokers and possible functional contribution. The identified differences provide new information to enrich our understanding of oral microbiota-brain axis interplay and their potential impact on mental health.

Bibliometric Analysis and Visualization Mapping of Anthrax Vaccine Publications from 1991 through 2021.

PURPOSE: This study aims to analyze and characterize anthrax vaccine-related research, key developments, global research trends, and mapping of published scientific research articles during the last three decades (1991-2021). METHODS: A bibliometric and visualized study was conducted. The Web of Science Core Collection database (WoSCC) was searched using relevant keywords ("Anthrax" OR "Anthrax bacterium" OR "Bacillus anthracis" OR "Bacteridium anthracis" OR "Bacillus cereus var. Anthracis" (Topic)) AND ("Vaccine" OR "Vaccines" OR "Immunization" OR "Immunisation" OR "Immunizations" OR "Immunisations" (Topic)) with specific restrictions. The data was analyzed and plotted by using different bibliometric software and tools (HistCiteTM software, version 12.3.17, Bibliometrix: An R-tool version 3.2.1, and VOSviewer software, version 1.6.17). RESULTS: The initial search yielded 1750 documents. After screening the titles and abstracts of the published studies, a total of 1090 articles published from 1991 to 2021 were included in the final analysis. These articles were published in 334 journals and were authored by 4567 authors from 64 countries with a collaboration index of 4.32. The annual scientific production growth rate was found to be 9.68%. The analyzed articles were cited 31335 times. The most productive year was 2006 (n = 77, 7.06%), while the most cited year was 2007 (2561 citations). The leading authors and journals in anthrax research were Rakesh Bhatnagar from Jawaharlal Nehru University, India (n = 35, 3.21%), and Vaccine (n = 1830, 16.51%), while the most cited author and journal were Arthur M. Friedlander from the United States Department of Defense (n = 2762), and Vaccine (n = 5696), respectively. The most studied recent research trend topics were lethal, double-blind, epidemiology, B surface antigen, disease, and toxin. The United States of America (USA) was the most dominant country in terms of publications, citations, corresponding author country, and global collaboration in anthrax vaccine research. The USA had the strongest collaboration with the United Kingdom (UK), China, Canada, Germany, and France. CONCLUSION: This is the first bibliometric study that provides a comprehensive historical overview of scientific studies. From 2006 to 2008, more than 20% of the total articles were published; however, a decrease was observed since 2013 in anthrax vaccine research. The developed countries made significant contributions to anthrax vaccine-related research, especially the USA. Among the top 10 leading authors, six authors are from the USA. The majority of the top leading institutions are also from the USA. About 90% of the total studies were funded by the United States Department of Health and Human Services (HHS), National Institutes of Health (NIH), USA, and the National Institute of Allergy and Infectious Diseases (NIAID), USA.

Untargeted Metabolomic Plasma Profiling of Emirati Dialysis Patients with Diabetes versus Non-Diabetic: A Pilot Study.

Diabetic kidney disease (DKD) is a severe irreversible complication of diabetes mellitus that further disturbs glucose metabolism. Identifying metabolic changes in the blood may provide early insight into DKD pathogenesis. This study aims to determine blood biomarkers differentiating DKD from non-diabetic kidney disease in the Emirati population utilizing the LC-MS/MS platform. Blood samples were collected from hemodialysis subjects with and without diabetes to detect indicators of pathological changes using an untargeted metabolomics approach. Metabolic profiles were analyzed based on clinically confirmed diabetic status and current HbA1c values. Five differentially significant metabolites were identified based on the clinically confirmed diabetic status, including hydroxyprogesterone and 3,4-Dihydroxymandelic acid. Similarly, we identified seven metabolites with apparent differences between Dialysis Diabetic (DD) and Dialysis non-Diabetic (DND) groups, including isovalerylglycine based on HbA1c values. Likewise, the top three metabolic pathways, including Tyrosine metabolism, were identified following the clinically confirmed diabetic status. As a result, nine different metabolites were enriched in the identified metabolic pathways, such as 3,4-Dihydroxymandelic acid. As a result, eleven different metabolites were enriched, including Glycerol. This study provides an insight into blood metabolic changes related to DKD that may lead to more effective management strategies.

Immune Profiling of COVID-19 in Correlation with SARS and MERS.

Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen.

Gut Microbiota Interplay With COVID-19 Reveals Links to Host Lipid Metabolism Among Middle Eastern Populations.

The interplay between the compositional changes in the gastrointestinal microbiome, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and severity, and host functions is complex and yet to be fully understood. This study performed 16S rRNA gene-based microbial profiling of 143 subjects. We observed structural and compositional alterations in the gut microbiota of the SARS-CoV-2-infected group in comparison to non-infected controls. The gut microbiota composition of the SARS-CoV-2-infected individuals showed an increase in anti-inflammatory bacteria such as Faecalibacterium (p-value = 1.72 × 10-6) and Bacteroides (p-value = 5.67 × 10-8). We also revealed a higher relative abundance of the highly beneficial butyrate producers such as Anaerostipes (p-value = 1.75 × 10-230), Lachnospiraceae (p-value = 7.14 × 10-65), and Blautia (p-value = 9.22 × 10-18) in the SARS-CoV-2-infected group in comparison to the control group. Moreover, phylogenetic investigation of communities by reconstructing unobserved state (PICRUSt) functional prediction analysis of the 16S rRNA gene abundance data showed substantial differences in the enrichment of metabolic pathways such as lipid, amino acid, carbohydrate, and xenobiotic metabolism, in comparison between both groups. We discovered an enrichment of linoleic acid, ether lipid, glycerolipid, and glycerophospholipid metabolism in the SARS-CoV-2-infected group, suggesting a link to SARS-CoV-2 entry and replication in host cells. We estimate the major contributing genera to the four pathways to be Parabacteroides, Streptococcus, Dorea, and Blautia, respectively. The identified differences provide a new insight to enrich our understanding of SARS-CoV-2-related changes in gut microbiota, their metabolic capabilities, and potential screening biomarkers linked to COVID-19 disease severity.

Correction: Exploring the impact of Helicobacter pylori on gut microbiome composition.

[This corrects the article DOI: 10.1371/journal.pone.0218274.].

L-WNK1 is required for BK channel activation in intercalated cells.

Large-conductance K+ (BK) channels expressed in intercalated cells (ICs) in the aldosterone-sensitive distal nephron (ASDN) mediate flow-induced K+ secretion. In the ASDN of mice and rabbits, IC BK channel expression and activity increase with a high-K+ diet. In cell culture, the long isoform of with-no-lysine kinase 1 (L-WNK1) increases BK channel expression and activity. Apical L-WNK1 expression is selectively enhanced in ICs in the ASDN of rabbits on a high-K+ diet, suggesting that L-WNK1 contributes to BK channel regulation by dietary K+. We examined the role of IC L-WNK1 expression in enhancing BK channel activity in response to a high-K+ diet. Mice with IC-selective deletion of L-WNK1 (IC-L-WNK1-KO) and littermate control mice were placed on a high-K+ (5% K+, as KCl) diet for 10 or more days. IC-L-WNK1-KO mice exhibited reduced IC apical + subapical α-subunit expression and BK channel-dependent whole cell currents compared with controls. Six-hour urinary K+ excretion in response a saline load was similar in IC-L-WNK1-KO mice and controls. The observations that IC-L-WNK1-KO mice on a high-K+ diet have higher blood K+ concentration and reduced IC BK channel activity are consistent with impaired urinary K+ secretion, demonstrating that IC L-WNK1 has a role in the renal adaptation to a high-K+ diet.NEW & NOTEWORTHY When mice are placed on a high-K+ diet, genetic disruption of the long form of with no lysine kinase 1 (L-WNK1) in intercalated cells reduced relative apical + subapical localization of the large-conductance K+ channel, blunted large-conductance K+ channel currents in intercalated cells, and increased blood K+ concentration. These data confirm an in vivo role of L-WNK1 in intercalated cells in adaptation to a high-K+ diet.