Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry.

BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong. METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short- to long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics. RESULTS: Overall, 123 subjects (median age 53 years, range 13-90 years; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 (range, 1-57.9) months. The most common indication for FMT was type 2 diabetes mellitus. The most common short-term adverse events within 1 month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new-onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, diabetes mellitus, or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched control subjects. CONCLUSIONS: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.

Human milk oligosaccharides in Chinese lactating mothers and relationship with allergy development in offspring.

BACKGROUND: The health benefits of breastfeeding are partly contributed by human milk oligosaccharides (HMOs), but there is limited data on breast milk (BM) HMO composition in Chinese. OBJECTIVE: This study investigated the association between early-life HMO intake and allergy occurrence in Chinese children. METHODS: 103 healthy Chinese pregnant women regardless of allergy history were recruited into this birth cohort. Their babies were followed until 24 months old. Concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), -sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) in BM collected at 1-month postpartum were measured by liquid chromatography-mass spectrometry. The associations between these HMOs and allergy occurrence by 24 months were analyzed by multivariate regression analyses. RESULTS: Twenty-nine percent and 19% of participants had eczema at 12 and 24 months old respectively. Eighty BM samples were analyzed, with 2'-FL being the most abundant HMO (median 1447 ppm, interquartile range [IQR] 291-1906 ppm), and median (IQR) levels of LNnT, 6'-SL and 3'-SL in ppm were 738 (580-950), 20.5 (12.7-38.8) and 23.0 (17.8-27.6) respectively. Participants with eczema by 24 months consumed BM with higher 2'-FL concentration at 1-month (P = 0.008), and also lower 6'-SL concentration in exclusively breastfed infants (P = 0.012) but higher 6'-SL concentration for those with mixed feeding at 1 month (P = 0.043). Food allergic children at 12 months consumed BM with higher 2'-FL concentrations at 1 month (P = 0.048). CONCLUSIONS: BM 2'-FL concentration is higher in children who develops eczema by 24 months and food allergy during infancy. The relationship for 6'-SL is divergent depending on mode of feeding in infants.

Short-term association among meteorological variation, outdoor air pollution and acute bronchiolitis in children in a subtropical setting.

OBJECTIVES: To examine the association among acute bronchiolitis-related hospitalisation in children, meteorological variation and outdoor air pollution. METHODS: We obtained the daily counts of acute bronchiolitis-related admission of children≤2 years old from all public hospitals, meteorological data and outdoor air pollutants' concentrations between 1 January 2008 and 31 December 2017 in Hong Kong. We used quasi-Poisson generalised additive models together with distributed lag non-linear models to estimate the associations of interest adjusted for confounders. RESULTS: A total of 29 688 admissions were included in the analysis. Increased adjusted relative risk (ARR) of acute bronchiolitis-related hospitalisation was associated with high temperature (ambient temperature and apparent temperature) and was marginally associated with high vapour pressure, a proxy for absolute humidity. High concentration of NO2 was associated with elevated risk of acute bronchiolitis admission; the risk of bronchiolitis hospitalisation increased statistically significantly with cumulative NO2 exposure over the range 66.2-119.6 µg/m3. For PM10, the significant effect observed at high concentrations appears to be immediate but not long lasting. For SO2, ARR increased as the concentration approached the 75th percentile and then decreased though the association was insignificant. CONCLUSIONS: Acute bronchiolitis-related hospitalisation among children was associated with temperature and exposure to NO2 and PM10 at different lag times, suggesting a need to adopt sustainable clean air policies, especially to target pollutants produced by motor vehicles, to protect young children's health.

The Extended C-Terminal Region of Influenza C Virus Nucleoprotein Is Important for Nuclear Import and Ribonucleoprotein Activity.

The influenza C virus (ICV) is a human-pathogenic agent, and the infections are frequently identified in children. Compared to influenza A and B viruses, the nucleoprotein of ICV (NPC) has an extended C-terminal region of which the functional significance is ill defined. We observed that the nuclear localization signals (NLSs) found on the nucleoproteins of influenza A and B virus subtypes are absent at corresponding positions on ICV. Instead, we found that a long bipartite nuclear localization signal resides at the extended C-terminal region, spanning from R513 to K549. Our experimental data determined that the KKMK motif within this region plays important roles in both nuclear import and polymerase activity. Similar to the influenza A viruses, NPC also binds to multiple human importin α isoforms. Taken together, our results enhance the understanding of the virus-host interaction of the influenza C virus.IMPORTANCE As a member of the Orthomyxoviridae family, the polymerase complex of the influenza C virus structurally resembles its influenza A and influenza B virus counterparts, but the nucleoprotein differs by possessing an extra C-terminal region. We have characterized this region in view of nuclear import and interaction with the importin α protein family. Our results demonstrate the functional significance of a previously uncharacterized region on Orthomyxoviridae nucleoprotein (NP). Based on this work, we propose that importin α binding to influenza C virus NP is regulated by a long bipartite nuclear localization signal. Since the sequence of influenza D virus NP shares high homology to that of the influenza C virus, this work will also shed light on how influenza D virus NP functions.

Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes.

BACKGROUND & AIMS: Patients with colorectal cancer (CRC) have a different gut microbiome signature than individuals without CRC. Little is known about the viral component of CRC-associated microbiome. We aimed to identify and validate viral taxonomic markers of CRC that might be used in detection of the disease or predicting outcome. METHODS: We performed shotgun metagenomic analyses of viromes of fecal samples from 74 patients with CRC (cases) and 92 individuals without CRC (controls) in Hong Kong (discovery cohort). Viral sequences were classified by taxonomic alignment against an integrated microbial reference genome database. Viral markers associated with CRC were validated using fecal samples from 3 separate cohorts: 111 patients with CRC and 112 controls in Hong Kong, 46 patients with CRC and 63 controls in Austria, and 91 patients with CRC and 66 controls in France and Germany. Using abundance profiles of CRC-associated virome genera, we constructed random survival forest models to identify those associated with patient survival times. RESULTS: The diversity of the gut bacteriophage community was significantly increased in patients with CRC compared with controls. Twenty-two viral taxa discriminated cases from controls with an area under the receiver operating characteristic curve of 0.802 in the discovery cohort. The viral markers were validated in 3 cohorts, with area under the receiver operating characteristic curves of 0.763, 0.736, and 0.715, respectively. Clinical subgroup analysis showed that dysbiosis of the gut virome was associated with early- and late-stage CRC. A combination of 4 taxonomic markers associated with reduced survival of patients with CRC (log-rank test, P = 8.1 × 10-6) independently of tumor stage, lymph node metastases, or clinical parameters. We found altered interactions between bacteriophages and oral bacterial commensals in fecal samples from patients with CRC compared with controls. CONCLUSIONS: In a metagenomic analysis of fecal samples from patients and controls, we identified virome signatures associated with CRC. These data might be used to develop tools to identify individuals with CRC or predict outcomes.

Molecular detection of respiratory pathogens and typing of human rhinovirus of adults hospitalized for exacerbation of asthma and chronic obstructive pulmonary disease.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma are associated with a variety of precipitating factors including infection. This study assessed the infective viral etiologies by real-time multiplex polymerase chain reaction of patients hospitalized with AECOPD and asthma exacerbations. In addition, infective etiologies were assessed for association with the clinical outcome of the patients. METHODS: Adults admitted with AECOPD and asthma exacerbations between August 2016 and July 2017 were recruited. Nasopharyngeal aspirate (NPA) samples were obtained from the patients within 1-2 days of admission and subjected to pathogen detection and human rhinovirus (HRV) typing. RESULTS: Altogether 402 patients with AECOPD, 80 stable COPD, 100 asthma exacerbation and 21 stable asthma subjects were recruited. Among those admitted for AECOPD and asthma exacerbations, 141(35.1%) and 45(45.0%) respectively had pathogens identified in the NPA specimens. The commonest virus identified was influenza A followed by HRV. HRV typing identified HRV-A and HRV-C as the more common HRV with a wide variety of genotypes. Identification of pathogens in NPA or HRV typing otherwise did not affect clinical outcomes including the hospital length of stay, readmission rates and mortality except that identification of pathogens in asthma exacerbation was associated with a lower rate of readmissions at 30 and 60 days. CONCLUSIONS: Many respiratory viruses were associated with AECOPD and asthma exacerbation. HRV-A and HRV-C were the more common HRV associated with exacerbations. Identification of pathogens in NPA was associated with less readmissions for asthma patients at 30 and 60 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT02866357 .

Nusbiarylins, a new class of antimicrobial agents: Rational design of bacterial transcription inhibitors targeting the interaction between the NusB and NusE proteins.

Discovery of antibiotics of a novel mode of action is highly required in the fierce battlefield with multi-drug resistant bacterial infections. Previously we have validated the protein-protein interaction between bacterial NusB and NusE proteins as an unprecedented antimicrobial target and reported the identification of a first-in-class inhibitor of bacterial ribosomal RNA synthesis with antimicrobial activities. In this paper, derivatives of the hit compound were rationally designed based on the pharmacophore model for chemical synthesis, followed by biological evaluations. Some of the derivatives demonstrated the improved antimicrobial activity with the minimum inhibitory concentration (MIC) at 1-2 µg/mL against clinically significant bacterial pathogens. Time-kill kinetics, confocal microscope, ATP production, cytotoxicity, hemolytic property and cell permeability using Caco-2 cells of a representative compound were also measured. This series of compounds were named "nusbiarylins" based on their target protein NusB and the biaryl structure and were expected to be further developed towards novel antimicrobial drug candidates in the near future.

IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza.

Background: We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods: A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death. Results: IFITM3 and TLR3 SNPs were in Hardy-Weinberg equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88) were comparable to 1000 Genomes Han Chinese data. We found over-representation of homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P = .04) genotypes among fatal cases. Recessive genetic models showed their significant independent associations with higher death risks (adjusted hazard ratio [aHR] 2.78, 95% confidence interval [CI] 1.29-6.02, and aHR 4.85, 95% CI 1.11-21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64-7.59 per risk genotype; aHR 9.99, 95% CI 1.27-78.59 with both). Results were consistent for each influenza subtype and other severity indicators. The CD55 TT genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions: Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.

Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis.

Our study aims to delineate the phenotypes of chronic neuropsychiatric symptoms among adult subjects recovering from their first COVID that occurred more than one year ago. We also aim to explore the clinical and socioeconomic risk factors of having a high loading of chronic neuropsychiatric symptoms. We recruited a post-COVID group who suffered from their first pre-Omicron COVID more than a year ago, and a control group who had never had COVID. The subjects completed app-based questionnaires on demographic, socioeconomic and health status, a COVID symptoms checklist, mental and sleep health measures, and neurocognitive tests. The post-COVID group has a statistically significantly higher level of fatigue compared to the control group (p < 0.001). Among the post-COVID group, the lack of any COVID vaccination before the first COVID and a higher level of material deprivation before the COVID pandemic predicts a higher load of chronic post-COVID neuropsychiatric symptoms. Partial correlation network analysis suggests that the chronic post-COVID neuropsychiatric symptoms can be clustered into two major (cognitive complaints -fatigue and anxiety-depression) and one minor (headache-dizziness) cluster. A higher level of material deprivation predicts a higher number of symptoms in both major clusters, but the lack of any COVID vaccination before the first COVID only predicts a higher number of symptoms in the cognitive complaints-fatigue cluster. Our result suggests heterogeneity among chronic post-COVID neuropsychiatric symptoms, which are associated with the complex interplay of biological and socioeconomic factors.

Predictive evolutionary modelling for influenza virus by site-based dynamics of mutations.

Influenza virus continuously evolves to escape human adaptive immunity and generates seasonal epidemics. Therefore, influenza vaccine strains need to be updated annually for the upcoming flu season to ensure vaccine effectiveness. We develop a computational approach, beth-1, to forecast virus evolution and select representative virus for influenza vaccine. The method involves modelling site-wise mutation fitness. Informed by virus genome and population sero-positivity, we calibrate transition time of mutations and project the fitness landscape to future time, based on which beth-1 selects the optimal vaccine strain. In season-to-season prediction in historical data for the influenza A pH1N1 and H3N2 viruses, beth-1 demonstrates superior genetic matching compared to existing approaches. In prospective validations, the model shows superior or non-inferior genetic matching and neutralization against circulating virus in mice immunization experiments compared to the current vaccine. The method offers a promising and ready-to-use tool to facilitate vaccine strain selection for the influenza virus through capturing heterogeneous evolutionary dynamics over genome space-time and linking molecular variants to population immune response.

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G.

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC â€‹= â€‹0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

Structural basis for RNA binding and homo-oligomer formation by influenza B virus nucleoprotein.

Influenza virus nucleoprotein (NP) is the major component of the viral ribonucleoprotein complex, which is crucial for the transcription and replication of the viral genome. We have determined the crystal structure of influenza B virus NP to a resolution of 3.2 Å. Influenza B NP contains a head, a body domain, and a tail loop. The electropositive groove between the head and body domains of influenza B NP is crucial for RNA binding. This groove also contains an extended flexible charged loop (amino acids [aa] 125 to 149), and two lysine clusters at the first half of this loop were shown to be crucial for binding RNA. Influenza B virus NP forms a crystallographic homotetramer by inserting the tail loop into the body domain of the neighboring NP molecule. A deeply buried salt bridge between R472 and E395 and a hydrophobic cluster at F468 are the major driving forces for the insertion. The analysis of the influenza B virus NP structure and function and comparisons with influenza A virus NP provide insights into the mechanisms of action and underpin efforts to design inhibitors for this class of proteins.

Effect of avian influenza A H5N1 infection on the expression of microRNA-141 in human respiratory epithelial cells.

BACKGROUND: Avian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host's miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. RESULTS: The results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-ß2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141. CONCLUSIONS: Since TGF-ß2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-ß2, we speculate that the modulation of TGF-ß2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.

Enterovirus infection among patients admitted to hospital in Hong Kong in 2010: epidemiology, clinical characteristics, and importance of molecular diagnosis.

The activity of hand, foot, and mouth disease (HFMD) in Hong Kong was high in 2010. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) had been performed routinely for diagnosis of enterovirus (EV) infection among hospitals in a geographical cluster. The aim of the study was to describe the epidemiology and the clinical pattern of EV-related hospital admission in 2010, and evaluate the impact of RT-PCR compared to conventional method. This was a retrospective study and patients with laboratory confirmed EV infection were included. Demographic information, clinical features, complications, and laboratory findings were analyzed. Among the 113 patients identified, HFMD was the most common presentation (84/113, 74%), followed by meningitis (10/113, 9%). Respiratory (52/113, 46%) and gastrointestinal symptoms like vomiting (36/113, 32%) and diarrhea (15/113, 13%) were quite common. For cases with central nervous system (CNS) or myocardial complications, there were significantly fewer oral ulcer and rash over hands and feet compared to their counter group. Serious infection mainly affected children younger than 1-year old and adults. Dual infection was noted among seven patients (6%). Compared to RT-PCR, conventional virus isolation detected only 14-16% of the infections. The relative low culture positive rate could be explained by the circulation of Coxsackie A6 in 2010 which was difficult to be isolated by cell culture. Diagnosis of EV infection among hospitalized patients may not be straightforward. EV RT-PCR significantly improved laboratory diagnosis and delineation of epidemiology of EV infection compared to conventional methods.

Transvaginal ultrasound probe contamination by the human papillomavirus in the emergency department.

OBJECTIVE: To determine if human papillomavirus (HPV) DNA can be detected on the transvaginal sonography (TVS) probe in the emergency department (ED) and whether the current barrier method plus disinfection can prevent HPV contamination of the TVS probe. METHODS: This was a two-part cross-sectional study. In the first part, surveillance samples were taken from the TVS probe for HPV DNA detection daily for 2 months. In the second part, patients presenting with early pregnancy complications were identified in the ED and high vaginal swabs were taken for HPV DNA testing. Several probe swabs were taken to identify if contamination was possible in cases where the procedure was done on an HPV carrier. RESULTS: A total of 120 surveillance samples were obtained, nine of which (7.5%) tested positive for HPV DNA. In the second part, 76 women were recruited, of whom 14 (18.4%) were HPV carriers. After the procedure and disinfection of the probe, three out of the 14 probe samples (21%) were HPV DNA positive. CONCLUSIONS: HPV is commonly encountered in the ED and contamination of the TVS probe with HPV is possible. Although it is difficult to prove the viability and infectivity of the virus, vigilant infection control measures should be maintained.

Interaction between Human Papillomavirus-Encoded E6 Protein and AurB Induces Cell Immortalization and Proliferation-A Potential Target of Intervention.

The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we identified, for the first time, that Aurora kinase B (AurB) is a bona fide interacting partner of E6. We systematically characterized the AurB-E6 complex formation and its consequences in carcinogenesis using a series of in vitro and cell-based assays. We also assessed the efficacy of Aurora kinase inhibitors in halting HPV-mediated carcinogenesis using in vitro and in vivo models. We showed that AurB activity was elevated in HPV-positive cells, and this correlated positively with the E6 protein level. E6 interacted directly with AurB in the nucleus or mitotic cells. A previously unidentified region of E6, located upstream of C-terminal E6-PBM, was important for AurB-E6 complex formation. AurB-E6 complex led to reduced AurB kinase activity. However, the AurB-E6 complex increased the hTERT protein level and its telomerase activity. On the other hand, AurB inhibition led to the inhibition of telomerase activity, cell proliferation, and tumor formation, even though this may occur in an HPV-independent manner. In summary, this study dissected the molecular mechanism of how E6 recruits AurB to induce cell immortalization and proliferation, leading to the eventual cancer development. Our findings revealed that the treatment of AZD1152 exerted a non-specific anti-tumor effect. Hence, a continuous effort to seek a specific and selective inhibitor that can halt HPV-mediated carcinogenesis should be warranted.

Characterization of METRNß as a novel biomarker of Coronavirus disease 2019 severity and prognosis.

Introduction: Coronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with predictive and prognostic value are crucial but lacking. Methods: Serum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNß detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNß levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNß in COVID-19. Results: The serum level of METRNß was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNß levels than survivors among the critical ones. METRNß concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNß level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNß and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNß was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave. Discussion: Our study uncovered the precise role of METRNß in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNß in triage therapeutic strategies.

Randomised clinical trial: Faecal microbiota transplantation for irritable bowel syndrome with diarrhoea.

BACKGROUND: Faecal microbiota transplantation (FMT) has been shown to improve symptoms in a proportion of patients with irritable bowel syndrome (IBS). AIM: We performed a randomised trial to assess the efficacy of FMT in patients with IBS. METHODS: We randomised 56 patients with diarrhoea-predominant IBS 1:1 to FMT or placebo via the duodenal route at baseline and week 4. The primary outcome was > 50 points decrease in IBS severity scoring system (IBS-SSS) score at week 12. Secondary outcomes were improvement in bloating and change in gut microbiota at week 12. After 12-week follow-up, those in the placebo group were assigned to receive open-label FMT. RESULTS: At week 12, 57.1% in the FMT group and 46.4% in the placebo group achieved the primary endpoint (p = 0.42). More patients receiving FMT than placebo had improvement in bloating (72% vs 30%; p = 0.005). In an open-label extension, 65.2% and 82.4% of patients achieved, respectively, the primary endpoint and improvement in bloating. Faecal microbiome of patients in the FMT group showed a reduction in bacteria like Ruminococcus gnavus and enrichment of bacteria such as Lawsonibacter at week 12, while no change in the placebo group. Functional analyses showed that the hydrogen sulphide-producing pathway decreased in patients who had FMT (p < 0.05) accompanied by a reduction in contributing bacteria. There were no serious adverse events related to FMT. CONCLUSION: FMT performed twice at an interval of four weeks did not significantly reduce IBS-SSS score. However, more patients had improvement in abdominal bloating, which was associated with a reduction in hydrogen sulphide-producing bacteria. (ClinicalTrials.gov NCT03125564).

Early-Life Skin Microbial Biomarkers for Eczema Phenotypes in Chinese Toddlers.

Eczema is a common inflammatory skin disorder during infancy. Evidence has shown that skin-microbiome fluctuations may precede eczema development, but their predictive value for eczema phenotypes remains unknown. We aimed to investigate the early-life evolution of the skin microbiome and its temporal associations with different pairs of eczema phenotypes (transient versus persistent, atopic versus non-atopic) in Chinese children. We followed 119 term Chinese infants from birth to 24 months old within a Hong Kong birth cohort. The skin microbes at the left antecubital fossa were serially sampled by flocked swabs at 1, 6, and 12 months for bacterial 16S rRNA gene sequencing. The atopic sensitization at 12 months was strongly associated with eczema persisting to 24 months (odds ratio 4.95, 95% confidence interval 1.29-19.01). Compared with those with non-atopic eczema, the children with atopic eczema had reduced alpha diversity at 12 months (p < 0.001) and transiently higher abundance of the genus Janibacter at 6 months (p < 0.001). Our findings suggest that atopic sensitization at 12 months may predict persistent eczema by 24 months, and atopic eczema at 12 months is associated with unique skin microbiome profiles at 6 and 12 months. Non-invasive skin-microbiome profiling may have predictive value for atopic eczema.