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

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

Microbial community structure and function in the gut of giant panda (Ailuropoda melanoleuca)

Giant pandas are unique animals because of their digestive system is similar to carnivores but they have in fact adapted to a plant diet with bamboo as their main food source. According to fossils records, giant pandas were omnivorous approximately 7 million years ago, becoming almost vegetarian after 4.6 to 5 million years of evolution. However, their genome and anatomical structure do not favor bamboo digestion. For more than a decade, researchers have been questioning the underlying mechanism of their ability to digest bamboo. In 2010, the genome of giant panda was completed, which confirmed that their genome had no gene encoding for cellulolytic enzymes. Thus, the gut microbiota of giant panda, which has been hypothesized to play a key role in bamboo digestion, has garnered unprecedented attention. Researchers are also interested in the giant panda’s gut microbes due to their potential application in biomass conversion. In Chapters 2 and 3 of this thesis, the microbial catalog of the giant panda’s gut microbiota was characterized, showing possible age-related microbial dysbiosis. Moreover, the microbiota, both bacterial and fungal was highly individualized because very few operational taxonomic units were shared among the four pandas in this study. Novel homoacetogens were also identified in the giant panda using functional gene clone-library sequencing. Using metagenomic sequencing, I uncovered the first evidence of human and animal related viruses in the giant panda’s gut. In addition to the community structure, I also determined the metabolic pathways of the microbiome. From KEGG annotation, a metabolic pathway for both cellulose and hemicellulose metabolism was identified. Comparative metagenomic analysis indicated that the giant panda’s gut microbiome was taxonomically and functionally distinct from those in mammals. In Chapters 4 and 5, a total of 97 species of bacteria were isolated and identified using biochemical assays. Four of these bacteria showed powerful cellulolytic and hemicellulolytic activities on solid media. The gram-positive bacteria (HKUOP_BS) and the gram-negative bacteria (HKUOP_A14) were found to be rod shaped, facultative anaerobes that had the ability to powerfully hydrolyze both cellulose and hemicellulose using intracellular and extracellular enzymes respectively. In Chapter 6, I determined the complete genome of a cellulolytic bacterium, Klebsiella oxytoca HKUOPL1, from giant panda and further described the annotated virulence, drug resistant, functional and potential horizontal transferring genes. The phylogenomic tree indicated that K. oxytoca HKUOPL1 closely resembled the K. oxytoca KCTC 1686 strain commonly used in 2,3-butanediol production. In captive giant pandas, a mucous excretion episode usually occurs with mild to severe colic. To understand the host-microbial interactions during this episode, bacterial communities were compared between mucous excreta and normal feces. The shifts in community abundance (especially flooding of Clostridia) may be associated with the mucous excretion episode. This study provides a better understanding of the microbial community structure and function in the giant panda’s gut.published_or_final_versionBiological SciencesDoctoralDoctor of Philosoph

Monitoring survivability and infectivity of porcine epidemic diarrhea virus (PEDv) in the infected on-farm earthen manure storages (EMS)

In recent years, porcine epidemic diarrhea virus (PEDv) has caused major epidemics, which has been a burden to North America's swine industry. Low infectious dose and high viability in the environment are major challenges in eradicating this virus. To further understand the survivability and infectivity of PEDv in the infected manure, we performed longitudinal monitoring in two open earthen manure storages (EMSs; previously referred to as lagoon) from two different infected swine farms identified in the province of Manitoba, Canada. Our study revealed that PEDv could survive up to nine months in the infected EMS after the initial outbreak in the farm. The viral load varied among different layers of the EMS with an average of 1.1 × 105 copies/ml of EMS, independent of EMS temperature and pH. In both studied EMSs, the evidence of viral replication was observed through increased viral load in the later weeks of the samplings while there was no new influx of infected manure into the EMSs, which was suggestive of presence of potential alternative hosts for PEDv within the EMSs. Decreasing infectivity of virus over time irrespective of increased viral load suggested the possibility of PEDv evolution within the EMS and perhaps in the new host that negatively impacted virus infectivity. Viral load in the top layer of the EMS was low and mostly non-infective suggesting that environmental factors, such as UV and sunlight, could diminish the replicability and infectivity of the virus. Thus, frequent agitation of the EMS that could expose virus to UV and sunlight might be a potential strategy for reduction of PEDv load and infectivity in the infected EMSs

Topology optimisation of wireless internet infrastructure

The paper discusses utilisation of the brute force methods for the task of towers distribution in wireless communication systems. The proposed algorithm allows to find an optimal allocation of a tower between the settlements. A simple wireless communication has been used as an example to investigate the functionality of the algorithm's software

Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype.

Over the past decade, emerging evidence has linked alterations in the gut microbial composition to a wide range of diseases including obesity, type 2 diabetes, and cardiovascular disease. Toll-like receptors (TLRs) are the major mediators for the interactions between gut microbiota and host innate immune system, which is involved in the localization and structuring of host gut microbiota. A previous study found that TLR5 deficient mice (TLR5KO1) had altered gut microbial composition which led to the development of metabolic syndrome including hyperlipidemia, hypertension, insulin resistance and increased adiposity. In the current study, a second TLR5-deficient mouse model was studied (TLR5KO2). TLR5 deficient mice did not manifest metabolic abnormalities related to the metabolic syndrome compared with littermate controls maintained on normal chow or after feeding a high fat diet. Analysis of the gut microbial composition of littermate TLR5KO2 and wild type mice revealed no significant difference in the overall microbiota structure between genotypes. However, the TLR5KO2 microbiota was distinctly different from that previously reported for TLR5KO1 mice with metabolic syndrome. We conclude that an altered composition of the microbiota in a given environment can result in metabolic syndrome, but it is not a consequence of TLR5 deficiency per se

Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA) or coral tumors are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB) were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch’s postulates in efforts to understand the etiology and progression of SGA