Gut virome in inflammatory bowel disease and beyond.

OBJECTIVE: The gut virome is a dense community of viruses inhabiting the gastrointestinal tract and an integral part of the microbiota. The virome coexists with the other components of the microbiota and with the host in a dynamic equilibrium, serving as a key contributor to the maintenance of intestinal homeostasis and functions. However, this equilibrium can be interrupted in certain pathological states, including inflammatory bowel disease, causing dysbiosis that may participate in disease pathogenesis. Nevertheless, whether virome dysbiosis is a causal or bystander event requires further clarification. DESIGN: This review seeks to summarise the latest advancements in the study of the gut virome, highlighting its cross-talk with the mucosal microenvironment. It explores how cutting-edge technologies may build upon current knowledge to advance research in this field. An overview of virome transplantation in diseased gastrointestinal tracts is provided along with insights into the development of innovative virome-based therapeutics to improve clinical management. RESULTS: Gut virome dysbiosis, primarily driven by the expansion of Caudovirales, has been shown to impact intestinal immunity and barrier functions, influencing overall intestinal homeostasis. Although emerging innovative technologies still need further implementation, they display the unprecedented potential to better characterise virome composition and delineate its role in intestinal diseases. CONCLUSIONS: The field of gut virome is progressively expanding, thanks to the advancements of sequencing technologies and bioinformatic pipelines. These have contributed to a better understanding of how virome dysbiosis is linked to intestinal disease pathogenesis and how the modulation of virome composition may help the clinical intervention to ameliorate gut disease management.

Multi-cohort analysis of depression-associated gut bacteria sheds insight on bacterial biomarkers across populations.

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of gut bacteria in the diagnostics and treatment of depression. To minimise heterogenicity in data analysis, the present meta-analysis adopted a standardised bioinformatics and statistical pipeline to analyse 16S rRNA sequences of 1827 samples from eight different cohorts. Although changes in the overall bacterial community were identified by our meta-analysis, depressive-correlated changes in alpha-diversity were absent. Enrichment of Bacteroidetes, Parabacteroides, Barnesiella, Bacteroides, and Bacteroides vulgatus, along with depletion in Firmicutes, Dialister, Oscillospiraceae UCG 003 and UCG 002, and Bacteroides plebeius, were observed in depressive-associated bacteria. By contrast, elevated L-glutamine degradation, and reduced L-glutamate and L-isoleucine biosynthesis were identified in depressive-associated microbiomes. After systemically reviewing the data of these collected cohorts, we have established a bacterial classifier to identify depressive symptoms with AUC 0.834 and 0.685 in the training and external validation dataset, respectively. Moreover, a low-risk bacterial cluster for depressive symptoms was identified, which was represented by a lower abundance of Escherichia-Shigella, and a higher abundance of Faecalibacterium, Oscillospiraceae UCG 002, Ruminococcus, and Christensenellaceae R.7 group.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events.

OBJECTIVE: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty). DESIGN: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA. RESULTS: We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05). CONCLUSION: Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.

Ethnicity Associations With Food Sensitization Are Mediated by Gut Microbiota Development in the First Year of Life.

BACKGROUND AND AIMS: Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children. METHODS: In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted. RESULTS: Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13-7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75-22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization. CONCLUSIONS: This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.

From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome.

BACKGROUND & AIMS: Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. METHODS: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. RESULTS: After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. CONCLUSIONS: Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

Evaluation of RT-qPCR Primer-Probe Sets to Inform Public Health Interventions Based on COVID-19 Sewage Tests.

Sewage surveillance is increasingly employed as a supplementary tool for COVID-19 control. Experiences learnt from large-scale trials could guide better interpretation of the sewage data for public health interventions. Here, we compared the performance of seven commonly used primer-probe sets in RT-qPCR and evaluated the usefulness in the sewage surveillance program in Hong Kong. All selected primer-probe sets reliably detected SARS-CoV-2 in pure water at 7 copies per µL. Sewage matrix did not influence RT-qPCR determination of SARS-CoV-2 concentrated from a small-volume sewage (30 mL) but introduced inhibitory impacts on a large-volume sewage (920 mL) with a ΔCt of 0.2-10.8. Diagnostic performance evaluation in finding COVID-19 cases showed that N1 was the best single primer-probe set, while the ORF1ab set is not recommended. Sewage surveillance using the N1 set for over 3200 samples effectively caught the outbreak trend and, importantly, had a 56% sensitivity and a 96% specificity in uncovering the signal sources from new cases and/or convalescent patients in the community. Our study paves the way for selecting detection primer-probe sets in wider applications in responding to the COVID-19 pandemic.

Cysteine protected cells from H2O2-induced damage and promoted long-chain fatty acids synthesis in vivo to improve γ-aminobutyric acid production in Levilactobacillus brevis.

Levilactobacillus brevis NPS-QW-145 isolated from kimchi is deficient in glutamate dehydrogenase-encoding gene (gdhA) to form glutamate, hence it required exogenous supplementation of glutamate/monosodium glutamate (MSG) for decarboxylation reaction to produce γ-aminobutyric acid (GABA). However, GABA conversion rate from MSG was relatively low. The individual effect of 20 amino acids on regulating GABA biosynthesis was investigated. Cysteine was selected to significantly improve GABA production from MSG. It was found that Lb. brevis was capable of producing H2O2, cysteine protected Lb. brevis against H2O2-induced oxidative damage to increase cell viability for the enhancement of GABA production. Moreover, cysteine promoted glucose consumption to produce acetyl-CoA for synthesizing long-chain fatty acids to significantly up-regulate GABA biosynthesis. These findings deciphered antioxidative capability of cysteine in Lb. brevis 145 and provided a theoretical basis for fatty acids synthesis-mediated GABA synthesis in Lb. brevis 145, and possibly in other lactic acid bacteria.

Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. METHODS: Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. RESULTS: Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. CONCLUSION: Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.

Saccharomyces cerevisiae fermentation products (SCFP) stabilize the ruminal microbiota of lactating dairy cows during periods of a depressed rumen pH.

BACKGROUND: Effects of Saccharomyces cerevisiae fermentation products (SCFP) on rumen microbiota were determined in vitro and in vivo under a high and a depressed pH. The in vitro trial determined the effects of Original XPC and NutriTek (Diamond V, Cedar Rapids, IA) at doses of 1.67 and 2.33 g/L, respectively, on the abundances of rumen bacteria under a high pH (> 6.3) and a depressed pH (5.8-6.0) using quantitative PCR (qPCR). In the in vivo trial eight rumen-cannulated lactating dairy cows were used in a cross-over design. Cows were randomly assigned to SCFP treatments (Original XPC, Diamond V, Cedar Rapids, IA) or control (No SCFP) before two 5-week experimental periods. During the second period, SCFP treatments were reversed. Cows on the SCFP treatment were supplemented with 14 g/d of SCFP and 126 g/d of ground corn. Other cows received 140 g/d ground corn. During the first 4 wk. of each period, cows received a basal diet containing 153 g/kg of starch. During week 5 of both periods, the rumen pH was depressed by a SARA challenge. This included replacing 208 g/kg of the basal diet with pellets of ground wheat and barley, resulting in a diet that contained 222 g/kg DM of starch. Microbial communities in rumen liquid digesta were examined by pyrosequencing, qPCR, and shotgun metagenomics. RESULTS: During the in vitro experiment, XPC and NutriTek increased the relative abundances of Ruminococcus flavefaciens, and Fibrobacter succinogenes determined at both the high and the depressed pH, with NutriTek having the largest effect. The relative abundances of Prevotella brevis, R. flavefaciens, ciliate protozoa, and Bifidobacterium spp. were increased by XPC in vivo. Adverse impacts of the in vivo SARA challenge included reductions of the richness and diversity of the rumen microbial community, the abundances of Bacteroidetes and ciliate protozoa in the rumen as determined by pyrosequencing, and the predicted functionality of rumen microbiota as determined by shotgun metagenomics. These reductions were attenuated by XPC supplementation. CONCLUSIONS: The negative effects of grain-based SARA challenges on the composition and predicted functionality of rumen microbiota are attenuated by supplementation with SCFP.

Selective Induction of Homeostatic Th17 Cells in the Murine Intestine by Cholera Toxin Interacting with the Microbiota.

Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype; that is, they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared with wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CT B subunit-specific serum IgG response in IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria in the small intestine of IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by segmented filamentous bacteria, but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expression of a panel of immune-regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a nonpathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.

Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children.

BACKGROUND: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight. METHODS: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2). INTERPRETATION: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3-4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.

Sex-specific impact of asthma during pregnancy on infant gut microbiota.

Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant.Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3-4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates.Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3-4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies.Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3-4 months of age, following maternal asthma during pregnancy.

Detection of Antibiotic Resistance Genes in Source and Drinking Water Samples from a First Nations Community in Canada.

UNLABELLED: Access to safe drinking water is now recognized as a human right by the United Nations. In developed countries like Canada, access to clean water is generally not a matter of concern. However, one in every five First Nations reserves is under a drinking water advisory, often due to unacceptable microbiological quality. In this study, we analyzed source and potable water from a First Nations community for the presence of coliform bacteria as well as various antibiotic resistance genes. Samples, including those from drinking water sources, were found to be positive for various antibiotic resistance genes, namely, ampC, tet(A), mecA, ß-lactamase genes (SHV-type, TEM-type, CTX-M-type, OXA-1, and CMY-2-type), and carbapenemase genes (KPC, IMP, VIM, NDM, GES, and OXA-48 genes). Not surprisingly, substantial numbers of total coliforms, including Escherichia coli, were recovered from these samples, and this result was also confirmed using Illumina sequencing of the 16S rRNA gene. These findings deserve further attention, as the presence of coliforms and antibiotic resistance genes potentially puts the health of the community members at risk. IMPORTANCE: In this study, we highlight the poor microbiological quality of drinking water in a First Nations community in Canada. We examined the coliform load as well as the presence of antibiotic resistance genes in these samples. This study examined the presence of antibiotic-resistant genes in drinking water samples from a First Nations Community in Canada. We believe that our findings are of considerable significance, since the issue of poor water quality in First Nations communities in Canada is often ignored, and our findings will help shed some light on this important issue.

An extended single-index multiplexed 16S rRNA sequencing for microbial community analysis on MiSeq illumina platforms.

The primary 16S rRNA sequencing protocol for microbial community analysis using Illumina platforms includes a single-indexing approach that allows pooling of hundreds of samples in each sequencing run. The protocol targets the V4 hypervariable region (HVR) of 16S rRNA using 150 bp paired-end (PE) sequencing. However, the latest improvement in Illumina chemistry has increased the read length up to 600 bp using 300 bp PE sequencing. To take advantage of the longer read length, a dual-indexing approach was previously developed for targeting different HVRs. However, due to simple working protocols, the single-index 150 bp PE approach still continues to be attractive to many researchers. Here, we described an extended single-indexing protocol for 300 bp PE illumina sequencing that targets the V3-V4 HVRs of 16S rRNA. The new primer set led to increased read length and alignment resolution, as well as increased richness and diversity of resulting microbial profile compared to that obtained from150 bp PE protocol for V4 sequencing. The ß-diversity profile also differed qualitatively and quantitatively between the two approaches. Both primer sets had high coverage rates and specificity to detect dominant phyla; however, their coverage rate with regards to the rare biosphere varied. Our data further confirms that the choice of primer is the most deterministic factor in sequencing coverage and specificity.

Why prescribe antibiotics? A systematic review of knowledge, tension, and motivation among clinicians in low-, middle- and high-income countries.

Medical professionals such as physicians and veterinarians are responsible for appropriate antimicrobial prescription (AMP) and use. Although seemingly straightforward, the factors influencing antibiotic prescription, a category of antimicrobials, are complex. Many studies have been conducted in the past two decades on this subject. As a result, there is a plethora of empirical evidence regarding the factors influencing clinicians' AMP practices. AIM: A systematic review of AMR studies on AMP was conducted, condensing findings according to a combination of the Knowledge, Attitude, and Practice (KAP) and Capacity, Opportunity, Motivation-Behavior (COM-B) models. Review findings were then synthesized and analyzed for policy implementation according to the Consolidated Framework for Implementation Research (CFIR). DESIGN AND METHODOLOGY: A systematic literature review was conducted according to PRISMA guidelines to identify peer-reviewed papers indexed in pre-determined medical science, social sciences, and humanities databases that apply the KAP model in their investigations. Antimicrobial prescription factors were compared and contrasted among low- and middle-income countries (LMICs) and high-income countries (HICs). FINDINGS: The KAP model is a heuristic and structured framework for identifying and classifying respondents' knowledge. However, other than medical knowledge, factors that influence prescription decision-making can be expanded to include attitudes, perception, personal affinities, professional circumstances, relational pressure, and social norms.

Virological response to nucleos(t)ide analogues treatment in chronic hepatitis B patients is associated with Bacteroides-dominant gut microbiome.

BACKGROUND: Gut dysbiosis is present in chronic hepatitis B virus (HBV) infection. In this study, we integrated microbiome and metabolome analysis to investigate the role of gut microbiome in virological response to nucleos(t)ide analogues (NAs) treatment. METHODS: Chronic HBV patients were prospectively recruited for steatosis and fibrosis assessments via liver elastography, with full-length 16S sequencing performed to identify the compositional gut microbiota differences. Fasting plasma bile acids were quantified by liquid chromatography-tandem mass spectrometry. FINDINGS: All patients (n = 110) were characterized into three distinct microbial clusters by their dominant genus: c-Bacteroides, c-Blautia, and c-Prevotella. Patients with c-Bacteroides had a higher plasma ursodeoxycholic acids (UDCA) level and an increase in 7-alpha-hydroxysteroid dehydrogenase (secondary bile acid biotransformation) than other clusters. In NAs-treated patients (n = 84), c-Bacteroides was associated with higher odds of plasma HBV-DNA undetectability when compared with non-c-Bacteroides clusters (OR 3.49, 95% CI 1.43-8.96, p = 0.01). c-Blautia was positively associated with advanced fibrosis (OR 2.74, 95% CI 1.09-7.31, p = 0.04). No such associations were found in treatment-naïve patients. Increased Escherichia coli relative abundance (0.21% vs. 0.03%, p = 0.035) was found in on-treatment patients (median treatment duration 98.1 months) with advanced fibrosis despite HBV DNA undetectability. An enrichment in l-tryptophan biosynthesis was observed in patients with advanced fibrosis, which exhibited a positive correlation with Escherichia coli. INTERPRETATION: Collectively, unique bacterial signatures, including c-Bacteroides and c-Blautia, were associated with virological undetectability and fibrosis evolution during NAs therapy in chronic HBV, setting up intriguing possibilities in optimizing HBV treatment. FUNDING: This study was supported by the Guangdong Natural Science Fund (2019A1515012003).

Prescribing antibiotics prudently-A survey of policy implementation drivers among physicians and veterinarians.

Background: As the antimicrobial resistance (AMR) problem accelerates, humans and animals are suffering from the consequences of infections with diminishing antimicrobial treatment options. Within the One Medicine and One Health mandate, which denotes a collaborative, multisectoral, and transdisciplinary approach to improve medicine and health across human and animal sectors, we investigate how human and veterinary medical practitioners apply their medical and policy knowledge in prescribing antimicrobials. Different regions and locations establish different intermediary policies and programs to support clinicians in that pursuit. In Hong Kong, there are locally adapted programs at governance and clinical levels in the human medical field. However, there is no locally adapted veterinary antibiotic prescription guideline or stewardship program, and veterinarians adopt overseas or international professions' antimicrobial use guidelines. Such a policy environment creates a natural experiment to compare local policy implementation conditions and clinicians' knowledge, perception, and practice. Method: We construct the investigative survey tool by adaptation of Knowledge, Attitude, and Practice (KAP) and Capacity, Opportunity, and Motivation-Behavior (COM-B) models. We identify, compare and contrast factors that influence clinicians' antimicrobial prescription behavior. The factors are considered both intrinsically, such as personal attributes, and extrinsically, such as societal and professional norms. Findings: The absence of locally adopted antimicrobial guidelines influences AMR stewardship program implementation in local Hong Kong veterinary community. As medical allies, physicians and veterinarians share similar demographic influence, organization considerations and perception of public awareness. Both cohorts prescribe more prudently with more years-in-practice, time available to communicate with patients or caretakers, and public awareness and support.