Papers by Dr Lindsey A Edwards BSc MSc DLSHTM PhD
American Journal of Physiology-Gastrointestinal and Liver Physiology
Decompensated cirrhotic patients, compared with compensated patients, exhibit a greater exaggerat... more Decompensated cirrhotic patients, compared with compensated patients, exhibit a greater exaggerated inflammatory response to bacterial products orchestrated by interferons, IL-6, and IL-8. Postbacterial product stimulation levels of a number of pro-inflammatory cytokines negatively correlate with liver disease severity biomarkers and liver disease severity scores raising the possibility that the switch to an immunodeficient phenotype in cirrhosis-associated immune dysfunction may commence earlier in the course of advanced liver disease.
Journal of Hepatology, 2018
Hepatology, 2018
International audienc
Gut, 2020
Cirrhotic portal hypertension is characterised by development of the decompensating events of asc... more Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mu...
American Journal of Gastroenterology, 2019
Oral, 2021
tree-level 2; and 'cooking methods' such as boiling, frying, formed tree-level 3. The association... more tree-level 2; and 'cooking methods' such as boiling, frying, formed tree-level 3. The associations between particular food intakes and health outcomes (presence of NAFLD and significant fibrosis, diabetes mellitus, hypertension, dyslipidaemia, and cardiovascular events) were determined by logistic regression. Results Individuals with NAFLD consumed significantly higher amount of cereals (as refined rice), fat and edible oils (as animal fat), meat (as red meat), sugar (as refined sugar) and fried foods, and lower amount of vegetables, pulses, nuts, seeds, and milk compared to controls (all P<0.05). Consumption of meat (as red meat), fats (as animal fat), nuts and refined rice was positively associated with both the presence of NAFLD and its severity (significant fibrosis), whereas, consumption of vegetables (as leafy vegetables), fruits, oily seeds, spices, and dried pulses was negatively associated with NAFLD. Fried and boiled food consumption were positively and negatively associated with NAFLD, respectively. Increased consumption of animal fats was associated with diabetes, hypertension, and cardiovascular outcomes, whereas consumption of wholegrain rice was negatively associated with these health-related outcomes. Conclusions Comprehensive evaluation of food intakes using validated FFQ and tree-based approach in a large, well-characterised population-based cases and controls has enabled the identification of specific dietary indicators associated with NAFLD, its severity and the co-morbidity cluster. These findings provide a basis for culturally sensitive advice to prevent the development of NAFLD as well as the design of individualised intervention in those with NAFLD.
Journal of Immunological Methods, 2020
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2016
Rejection of donor organs depends on the trafficking of donor passenger leukocytes to the seconda... more Rejection of donor organs depends on the trafficking of donor passenger leukocytes to the secondary lymphoid organs of the recipient to elicit an immune response via the direct antigen presentation pathway. Therefore, the depletion of passenger leukocytes may be clinically applicable as a strategy to improve graft survival. Because major histocompatibility complex (MHC) class II(+) cells are most efficient at inducing immune responses, selective depletion of this population from donor grafts may dampen the alloimmune response and prolong graft survival. In a fully MHC mismatched mouse kidney allograft model, we describe the synthesis of an immunotoxin, consisting of the F(ab')2 fragment of a monoclonal antibody against the donor MHC class II molecule I-A(k) conjugated with the plant-derived ribosomal inactivating protein gelonin. This anti-I-A(k) gelonin immunotoxin depletes I-A(k) expressing cells specifically in vitro and in vivo. When given to recipients of kidney allografts,...
The Cardiac Lymphatic System, 2013
Cardiac transplantation is an important form of treatment for patients with end-stage heart failu... more Cardiac transplantation is an important form of treatment for patients with end-stage heart failure. Rejection by the immune system of the recipient is a major cause of graft loss. The lymphatic system plays a crucial role in the immune response, but has not received much attention. Donor blood vessels are joined to those of the recipient during the transplant operation; however, due to their small size, donor lymphatic vessels are not reconnected. For this same reason the imaging of lymphatics, and therefore the understanding of this system, has been hampered. In recent years great strides have been made towards developing new imaging modalities that allow the lymphatic system to be imaged in a non-invasive or semi-invasive manner. Not only does this imaging provide new insights into the lymphatic system, it also presents the possibility of using lymphatic imaging to diagnose and monitor diseases and their treatment. In the case of heart transplantation, which will be the focus of this chapter, the lymphatic system has been shown to play a role in the alloimmune response. Imaging may be used as an extra tool for patient monitoring or as a research tool to develop new treatment protocols for recipients of cardiac transplants.
Frontiers in Public Health, 2016
Infection and immunity, Jan 12, 2015
Although the importance of alveolar macrophages for host immunity during early Streptococcus pneu... more Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors is less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, the capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model after infection with a high dose inoculum of encapsulated S. pneumoniae alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 minutes compared to 135 minute...
Changes in microbial metabolism have been used as the main approach to assess function and elucid... more Changes in microbial metabolism have been used as the main approach to assess function and elucidate environmental and host-microbiome interactions. This can be hampered by uncharacterised metagenome species and lack of metabolic annotation. To address this, we present a comprehensive computational platform for population stratification based on microbiome composition, the underlying metabolic potential and generation of metagenome species and community level metabolic models. We revisit the concepts of enterotype and microbiome richness introducing the reactobiome as a stratification method to unravel the metabolic features of the human gut microbiome. The reactobiome encapsulates resilience and microbiome dysbiosis at a functional level. We describe five reactotypes in healthy populations from 16 countries, with specific amino acid, carbohydrate and xenobiotic metabolic features. The validity of the approach was tested to unravel host-microbiome and environmental interactions by a...
JHEP Reports
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The role of gut microbiota in humans is of great interest, and metagenomics provided the possibil... more The role of gut microbiota in humans is of great interest, and metagenomics provided the possibilities for extensively analysing bacterial diversity in health and disease. Here we explored the human gut microbiome samples across 19 countries, performing compositional, functional and integrative analysis. To complement these data and analyse the stability of the microbiome, we followed 86 healthy Swedish individuals over one year, with four sampling times and extensive clinical phenotyping. The integrative analysis of temporal microbiome changes shows the existence of two types of species with a tendency to vary in abundance with time, here called outflow and inflow species. Importantly, the former tends to be enriched in disease, while the latter is enriched in health. We suggest that the decrease of disease-associated outflow and the increase of health-associated inflow species with time may be a fundamental albeit previously unrecognized aspect of the homeostasis maintenance in a ...
Journal of clinical apheresis, Jan 15, 2018
Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids.... more Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments. Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear r...
Circulation, Jan 3, 2017
Background -Cardiac transplantation is an excellent treatment for end-stage heart disease. Howeve... more Background -Cardiac transplantation is an excellent treatment for end-stage heart disease. However, rejection of the donor graft, particularly by chronic rejection leading to cardiac allograft vasculopathy, remains a major cause of graft loss. The lymphatic system plays a crucial role in the alloimmune response, facilitating trafficking of antigen presenting cells (APCs) to draining lymph nodes (dLN). The encounter of APCs with T lymphocytes in secondary lymphoid organs is essential for the initiation of alloimmunity. Donor lymphatic vessels are not anastomosed to that of the recipient during transplantation. The pathophysiology of lymphatic disruption is unknown and whether this disruption enhances or hinders the alloimmune responses is unclear. Although histological analysis of lymphatic vessels in donor grafts can yield information on the structure of the lymphatics, the function, however, following cardiac transplantation is poorly understood. Methods -Using Single photon emissi...
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Papers by Dr Lindsey A Edwards BSc MSc DLSHTM PhD