Discovering novel Cathepsin L inhibitors from natural products using artificial intelligence.

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited. In this study, we used a combination of artificial intelligence and experimental methods to identify new CTSL inhibitors from natural products. Through a robust deep learning model and molecular docking, we screened 150 molecules from natural products for experimental validation. At a concentration of 100 µM, we found that 36 of them exhibited more than 50 % inhibition of CTSL. Notably, 13 molecules displayed over 90 % inhibition and exhibiting concentration-dependent effects. The molecular dynamics simulation on the two most potent inhibitors, Plumbagin and Beta-Lapachone, demonstrated stable interaction at the CTSL active site. Enzyme kinetics studies have shown that these inhibitors exert an uncompetitive inhibitory effect on CTSL. In conclusion, our research identifies Plumbagin and Beta-Lapachone as potential CTSL inhibitors, offering promising candidates for the treatment of metabolic disorders and illustrating the effectiveness of artificial intelligence in drug discovery.

Upper respiratory Streptococcus pneumoniae colonization among working-age adults with prevalent exposure to overcrowding.

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged <5 years [odds ratio (OR) = 1.45 (0.95-2.20)] and overcrowding [OR = 1.48 (0.96-2.30) and 2.84 (1.20-6.73), respectively, for participants in households with >2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged <5 years [OR = 2.05 (1.18-3.59) for participants living in households with >2 vs ≤2 persons per bedroom]. Exposure to children aged <5 years and overcrowding were each associated with increased pneumococcal density among carriers [piaB cT difference of 2.04 (0.36-3.73) and 2.44 (0.80-4.11), respectively]. While exposure to young children was a predictor of pneumococcal carriage, associations of overcrowding with increased prevalence and density of carriage in households without young children suggest that transmission also occurs among adults in close-contact settings.IMPORTANCEAlthough infants and older adults are the groups most commonly affected by pneumococcal disease, outbreaks are known to occur among healthy, working-age populations exposed to overcrowding, including miners, shipyard workers, military recruits, and prisoners. Carriage of Streptococcus pneumoniae is the precursor to pneumococcal disease, and its relation to overcrowding in adult populations is poorly understood. We used molecular methods to characterize pneumococcal carriage in culture-enriched saliva samples from low-income adult farmworkers in Monterey County, CA. While exposure to children in the household was an important risk factor for pneumococcal carriage, living in an overcrowded household without young children was an independent predictor of carriage as well. Moreover, participants exposed to children or overcrowding carried pneumococci at higher density than those without such exposures, suggesting recent transmission. Our findings suggest that, in addition to transmission from young children, pneumococcal transmission may occur independently among adults in overcrowded settings.

What determines the vote-seeking behavior of legislators in South Korea?

Pre-existing studies suggest that legislators in small districts tend to be more responsive to the electorate than those in large districts, as accountability is typically clearer in a smaller setting. However, it is not clear whether the relationship between district size and legislators' constituency-oriented spending holds in other electoral settings (e.g., South Korea), where pork barrel benefits tend to be determined at the administrative unit, not the electoral district. The present study hypothesizes that as the number of legislators in an administrative unit increases, they are less likely to try to appeal to the voters. Additionally, this study examines the moderating effects of partisan homogeneity and legislators' seniority. The results from the statistical analysis of data from Korean National Assembly members confirm our hypothesis: the number of legislators in an administrative unit turns out to be negatively associated with their vote-seeking behavior. Such a relationship tends to be strong in administrative units co-represented by multiple parties and weak among newly elected legislators.

Erythema nodosum as an unusual skin manifestation of long COVID: A case report.

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.

Childhood Arthritis and Rheumatology Research Alliance Biologic DMARD Consensus Treatment Plans for Refractory Moderately Severe Juvenile Dermatomyositis.

OBJECTIVE: The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM. RESULTS: Four bDMARD CTPs were proposed: TNF-alpha inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67/72]) as well as for patient characteristics, assessments, outcome measures, and follow up. By weighted average, respondents indicated that they would most likely use rituximab followed by abatacept, TNF-alpha inhibitor, and tocilizumab. CONCLUSION: CTPs for the use of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.

HLA-DPB1*05:01 and HLA-A*11:01 Is Associated with Adverse Drug Reactions to Isoniazid and Rifampin for Treatment of Latent Tuberculosis Infection in South Korea.

Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H-) compared to the control group (DHS-/H-) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415-59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493-21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110-92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

Long-term impact of late pulmonary hypertension requiring medication in extremely preterm infants with severe bronchopulmonary dysplasia.

This study investigated whether late pulmonary hypertension (LPH) independently increases the risk of long-term mortality or neurodevelopmental delay (NDD) in extremely preterm infants (EPIs) with severe bronchopulmonary dysplasia (BPD). Using prospectively collected data from the Korean Neonatal Network, we included EPIs with severe BPD born at 22-27 weeks' gestation between 2013 and 2021. EPIs having severe BPD with LPH (LPH, n = 124) were matched 1:3 with those without pulmonary hypertension (PH) as controls (CON, n = 372), via propensity score matching. LPH was defined as PH with the initiation of medication after 36 weeks' corrected age (CA). Long-term mortality after 36 weeks' CA or NDD at 18-24 months' CA was analyzed. NDD was assessed using composite scores based on various neurodevelopmental assessment modalities. LPH had significantly higher long-term mortality or NDD (45.2% vs. 23.1%, P < 0.001), mortality (24.2% vs. 4.84%, P < 0.001), and NDD (68.4% vs. 37.8%, P = 0.001), respectively than CON, even after adjusting for different demographic factors. Multivariable regression demonstrated that LPH independently increased the risk of mortality or NDD (adjusted odds ratio, 1.95; 95% confidence intervals, 1.17-3.25). When LPH occurs in EPIs with severe BPD, special monitoring and meticulous care for long-term survival and neurodevelopment are continuously needed.

Combined DNA Methylation and Gastric Microbiome Marker Predicts Helicobacter pylori-Negative Gastric Cancer.

Background/Aims: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. Methods: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. Results: The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q<0.05). MIR124-3 and TWIST1 methylation levels were higher in patients with IM than those with CG and also in those with GC than in those with IM (all q<0.05). A higher methylation level of TWIST1 was an independent predictor for H. pylori-negative GC after adjusting for age, sex, and atrophy (odds ratio [OR], 15.15; 95% confidence interval [CI], 1.58 to 145.46; p=0.018). The combination of TWIST1 methylation and GC microbiome index (a microbiome marker) was significantly associated with H. pylori-negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024). Conclusions: The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting H. pylori-negative GC.

Impact of Mandated Insurance Coverage of Assisted Reproductive Technology on Clinic Website Transparency.

Objective: The purpose of this study was to determine whether website transparency of service costs, accepted insurance plans, and financing options differs between reproductive endocrinology and infertility clinics located in states that do and do not mandate insurance coverage of assisted reproductive technology (ART). Methods: Six hundred forty-six clinics were identified using the Society for Assisted Reproductive Technology online locator. Clinics were excluded for missing website links, duplicate entries, broken websites, or permanent closure. Mandated coverage by state was gathered on resolve.org Chi-squared testing and logistic regression were performed. Results: Of the 311 clinic websites analyzed, 28.6% were in states that mandate ART coverage and 71.4% were not. Clinics in states that have mandated coverage were more likely to list specific prices on their websites. These clinics were 2.13 times more likely to list specific costs (odds ratio [OR]; 95% confidence interval [CI]: 1.19-3.81, p = 0.01). There was also a significant difference between the percent of clinics in mandated coverage states and nonmandated states that listed accepted insurance plans. These clinics were 2.44 times more likely to report accepted insurance plans (OR; 95% CI: [1.47-4.05], p = 0.005). There was no significant difference in the mention of financial assistance between the groups. Clinics in states with mandated coverage were more likely to mention discount programs, but there was no significant difference for other types of financial assistance. Conclusion: Clinics located in states that mandate insurance coverage of ART are more likely to list specific costs, accepted insurance plans, and the availability of discount programs on their website. Patients living in states without mandated coverage are more likely to need to finance their own treatment, yet these patients are less likely to have nearby clinics that provide financial transparency on their websites.

Updates on efficacy and safety janus kinase inhibitors in juvenile dermatomyositis.

INTRODUCTION: Juvenile dermatomyositis (JDM) is a rare autoimmune disease most commonly with proximal weakness due to inflammation and characteristic skin rashes. Most patients have a chronic or polycyclic disease course on standard therapy so better treatments are needed. An interferon signature is well-established in key tissues of JDM. Janus kinase inhibitors (jakinibs), which can decrease IFN signaling, are therefore appealing as a targeted therapy. AREAS COVERED: Herein is a review of the growing literature on JDM patients in jakinibs, including specifics of their jakinib exposure, summary of efficacy, disease features, and characteristics of patients treated, and safety parameters. EXPERT OPINION: The vast majority of refractory JDM patients respond to jakinib therapy, though they have varied features, doses, and previous/concurrent medications, and data is largely retrospective. Jakinibs are an exciting and promising treatment in JDM. Evaluation with larger prospective controlled studies is needed to answer remaining questions about jakinibs in JDM regarding dosing, which JDM patients to treat with jakinibs, potential biomarkers to use, and how best to monitor safety risks in JDM.

Successful surgical attenuation of portosystemic shunt in a dog with imaging-diagnosed portal vein aplasia.

An 8-month-old female Maltese dog was referred for examination with a history of circling, dullness, and drooling. Serum biochemical analysis revealed hyperammonemia, with microhepatica observed on radiography. Computed tomography angiography revealed a portosystemic shunt originating from the right gastric vein and inserting into the prehepatic caudal vena cava. Portal blood flow to the liver was not observed. Based on computed tomography angiography, the dog was tentatively diagnosed with portosystemic shunt with portal vein aplasia. An exploratory laparotomy was done to obtain a definitive diagnosis. The dog had no subjective clinical signs of portal hypertension during a temporary occlusion test of the portosystemic shunt. A thin-film band was placed around the portosystemic shunt to achieve partial attenuation. There was no evidence of hepatic encephalopathy in the long term after surgery, and the dog's liver volume increased over time. Computed tomography angiography at 6 mo after surgery identified well-visualized intrahepatic portal branches. Key clinical message: We inferred that a direct occlusion test is a reliable diagnostic technique that overcomes the limitations of diagnostic imaging methods, including computed tomography angiography, and is a good technique for determining whether surgical attenuation is possible in dogs with suspected portal vein aplasia.

Atténuation chirurgicale réussie d'un shunt porto-systémique chez un chien avec une aplasie de la veine porte diagnostiquée par imagerie. Une femelle bichon maltais âgée de 8 mois a été référée pour examen avec une histoire de tournis, apathie et salivation excessive. L'analyse biochimique du sérum a révélé une hyperammionémie, avec un petit foie observé lors des radiographies. Une angiographie par tomodensitométrie a révélé un shunt porto-systémique prenant son origine de la veine gastrique droite et s'insérant dans la veine cave caudale pré-hépatique. Le flot sanguin porte au foie n'était pas observé. Sur la base de l'angiographie par tomodensitométrie, un diagnostic présumé de shunt porto-systémique avec aplasie de la veine porte a été émis. Une laparotomie exploratoire a été effectuée afin d'obtenir un diagnostic définitif. Le chien ne présentait pas de signe clinique subjectif d'hypertension portale durant un test d'occlusion temporaire du shunt porto-systémique. Une bande de film mince a été placée autour du shunt porto-systémique pour causer une réduction partielle. Il n'y avait aucune évidence d'encéphalopathie hépatique à long terme après la chirurgie, et le volume du foie du chien a augmenté dans le temps. Une angiographie par tomodensitométrie effectuée 6 mo après la chirurgie a permis de bien visualiser des branches portes intra-hépatiques.Message clinique clé :Nous avons déduit qu'un test d'occlusion est une technique diagnostique fiable qui surpasse les limites des méthodes d'imagerie diagnostique, incluant l'angiographie par tomodensitométrie, et est une bonne technique pour déterminer si une réduction chirurgicale est possible chez des chiens chez qui on soupçonne une aplasie de la veine porte.(Traduit par Dr Serge Messier).

Genome-wide association study implicates the role of TBXAS1 in the pathogenesis of depressive symptoms among the Korean population.

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10-8; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15-1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms.

Human papillomavirus Detection Rates in Bowen's Disease: Correlation with Pelvic and Digital Region Involvement and Specific p53 Immunostaining Patterns.

BACKGROUND: The relationship between human papillomavirus (HPV) and Bowen's disease (BD) is not fully understood. OBJECTIVES: To investigate the differences in HPV detection rates in BD samples across various body regions and analyze the expression patterns of p53, p16, and Ki-67 in relation to HPV presence. METHODS: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53, and Ki-67 was performed. RESULTS: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (69.2%, P<0.001) and digital (50.0%, P=0.022) areas compared to those in the other regions. HPV presence was significantly correlated with p53 negativity (P=0.002), the p53 "non-overexpression" IHC pattern (P<0.001), and p53-p16 immunostain pattern discordance (P<0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern, or Ki-67 expression. CONCLUSIONS: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in pathogenesis of BD in the pelvic and digital regions.

The Association Between Maternal Depressive Symptoms and Toddlers' Developmental and Behavioral Problems: A Population-Based Study.

This study aims to compare the developmental-behavioral profiles of 2-year-olds of mothers who experienced postpartum and/or current depression with profiles of toddlers of mothers without depression at either time using population-based Rhode Island data. Weighted data from Rhode Island Department of Health's Pregnancy Risk Assessment Monitoring System and Rhode Island's follow-up Toddlers Wellness Overview Survey distributed to mothers giving birth between 2006 and 2008 were analyzed. Compared with non-depressed mothers, those with any depression following childbirth reported more concerns with their toddlers' receptive language, social-emotional development, and their sleep and feeding behaviors. When adjusted for demographics, persistent depression remained associated with social-emotional (adjusted odds ratio [aOR] = 7.53, 2.78-20.34) and feeding concerns (aOR = 3.13, 1.36-7.22), and current depression was associated with social-emotional concerns (aOR = 2.52, 1.26-5.01). We conclude that pediatric providers should explore maternal mental health as a mediating and potentially modifiable factor beyond the postpartum period when toddlers present with developmental-behavioral challenges.

Association between long-term PM2.5 exposure and risk of Kawasaki disease in children: A nationwide longitudinal cohort study.

BACKGROUND: Based on previous studies suggesting air pollution as a potential risk factor for Kawasaki Disease (KD), we examined the association of long-term exposure to childhood fine particulate matter (PM2.5) with the risk of KD. METHODS: We used National Health Insurance Service-National Sample Cohort data from 2002 to 2019, which included beneficiaries aged 0 years at enrollment and followed-up until the onset of KD or age 5 years. The onset of KD was defined as the first hospital visit record with a primary diagnostic code of M30.3, based on the 10th revision of the International Classification of Diseases, and with an intravenous immunoglobulin (IVIG) prescription. We assigned PM2.5 concentrations to 226 districts, based on mean annual predictions from a machine learning-based ensemble prediction model. We performed Cox proportional-hazards modeling with time-varying exposures and confounders. RESULTS: We identified 134,634 individuals aged five or less at enrollment and, of these, 1220 individuals who had a KD onset and an IVIG prescription during study period. The average annual concentration of PM2.5 exposed to the entire cohort was 28.2 µg/m³ (Standard Deviation 2.9). For each 5 µg/m³ increase in annual PM2.5 concentration, the hazard ratio of KD was 1.21 (95% CI 1.05-1.39). CONCLUSIONS: In this nationwide, population-based, cohort study, long-term childhood exposure to PM2.5 was associated with an increased incidence of KD in children. The study highlights plausible mechanisms for the association between PM2.5 and KD, but further studies are needed to confirm our findings.

Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals. APPROACH AND RESULTS: A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice. CONCLUSIONS: Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.