Role of Gut Microbiota in Cardiovascular Disease that Links to Host Genotype and Diet

Cardiovascular diseases (CVDs) are major outcomes of metabolic impairments in humans, which result from several genetic and environmental factors. In recent years, a ‘microbiome hypothesis’ has been proposed as a result of several studies that have attempted to understand underlying mechanisms of CVDs. Similar to CVDs, both genetic and environmental factors, especially diets, have a major impact on shaping gut microbiota and their functions. In the past decade, strong evidence has emerged to confirm the role of gut microbiota in contributing to the onset of CVDs. However, a comprehensive understanding of interactions among diet, host genotype, gut microbiota and CVDs is still facing challenges due to the complicated nature of CVDs. In this chapter, we review the present state of our knowledge about the contributory role of gut microbiota in CVDs and discuss the knowledge gaps that warrant further investigations. Moreover, we review the potential intervention strategies that may target the microbiota-driven pathology in CVDs and discuss the strength and weakness of animal models in studying the roles of gut microbiota in CVDs

Genetic diversity and multiple introductions of porcine reproductive and respiratory syndrome viruses in Thailand

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent in Thailand, causing a huge impact on the country's swine industry. Yet the diversity and origin of these Thai PRRSVs remained vague. In this context, we collected all the Thai PRRSV sequences described earlier and incorporated them into the global diversity. The results indicated that PRRSVs in Thailand were originated from multiple introductions involving both Type 1 and Type 2 PRRSVs. Many of the introductions were followed by extensive geographic expansion, causing regional co-circulation of diverse PRRSV variants in three major pig-producing provinces. Based on these results, we suggest (1) to avoid blind vaccination and to apply vaccines tailor-made for target diversity, (2) to monitor pig importation and transportation, and (3) to implement a better biosecurity to reduce horizontal transmissions as three potentially effective strategies of controlling PRRS in Thailand

The role of the gut-microbiome-brain axis in metabolic remodeling amongst children with cerebral palsy and epilepsy

BackgroundEpilepsy-associated dysbiosis in gut microbiota has been previously described, but the mechanistic roles of the gut microbiome in epileptogenesis among children with cerebral palsy (CP) have yet to be illustrated.MethodsUsing shotgun metagenomic sequencing coupled with untargeted metabolomics analysis, this observational study compared the gut microbiome and metabolome of eight children with non-epileptic cerebral palsy (NECP) to those of 13 children with cerebral palsy with epilepsy (CPE). Among children with CPE, 8 had drug-sensitive epilepsy (DSE) and five had drug-resistant epilepsy (DRE). Characteristics at enrollment, medication history, and 7-day dietary intake were compared between groups.ResultsAt the species level, CPE subjects had significantly lower abundances of Bacteroides fragilis and Dialister invisus but higher abundances of Phascolarctobacterium faecium and Eubacterium limosum. By contrast, DRE subjects had a significantly higher colonization of Veillonella parvula. Regarding microbial functional pathways, CPE subjects had decreased abundances of pathways for serine degradation, quinolinic acid degradation, glutamate degradation I, glycerol degradation, sulfate reduction, and nitrate reduction but increased abundances of pathways related to ethanol production. As for metabolites, CPE subjects had higher concentrations of kynurenic acid, 2-oxindole, dopamine, 2-hydroxyphenyalanine, 3,4–dihydroxyphenylglycol, L-tartaric acid, and D-saccharic acid; DRE subjects had increased concentrations of indole and homovanilic acid.ConclusionsIn this study, we found evidence of gut dysbiosis amongst children with cerebral palsy and epilepsy in terms of gut microbiota species, functional pathways, and metabolites. The combined metagenomic and metabolomic analyses have shed insights on the potential roles of B. fragilis and D. invisus in neuroprotection. The combined analyses have also provided evidence for the involvement of GMBA in the epilepsy-related dysbiosis of kynurenine, serotonin, and dopamine pathways and their complex interplay with neuroimmune and neuroendocrinological pathways

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial

Background: To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin–piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. Methods: We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50–1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin–piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. Findings: Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was −10·6% (95% CI −15·1 to −6·1; p=0·0008) at month 3 and −4·5% (−10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. Interpretation: In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. Funding: The Global Fund to Fight AIDS, Tuberculosis and Malaria

Epidemiology and risk factors for Carbapenemase-Producing Enterobacteriaceae carriage in the hospital: a population-based nested case-control study

Objective: This study aims to study the epidemiology of Carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. / Methods: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. / Results: From 1st January 2008 to 31st December 2019, 8,588 patients received CPE genotyping tests, and 2,353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics [Odds ratio:1.37 (1.22-1.53), p<.001] was found as an independent risk factor for carriage of CPE. / Conclusion: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE. / Summary: The incidence rate of Carbapenemase-producing Enterobacteriaceae is increasing in Hong Kong, with the predominant enzyme of class B carbapenemase. With multivariable conditional logistic regression, the previous use of any beta-lactam antibiotics was found as an independent risk factor for CPE carriage

Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy

Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula feeding, and antibiotic use. We undertook this study to apply the significance analysis of microarrays (SAM) method to quantify changes in gut microbial composition during later infancy following the most common birth and postnatal exposures affecting infant gut microbial composition. Gut microbiota of 166 full-term infants in the Canadian Healthy Infant Longitudinal Development birth cohort were profiled using 16S high-throughput gene sequencing. Infants were placed into groups according to mutually exclusive combinations of birth mode (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use (yes/no) by 3 months of age. Based on repeated permutations of data and adjustment for the false discovery rate, the SAM statistic identified statistically significant changes in gut microbial abundance between 3 months and 1 year of age within each infant group. We observed well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with other perinatal co-exposures; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. With and without antibiotic exposure, the absence of a breast milk diet by 3 months of age following vaginal birth yielded a higher proportion of unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy, and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota. Gut microbiota of infants born vaginally and exclusively formula fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae, and exhibited a greater decline in the Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization