Beyond climate change and health: Integrating broader environmental change and natural environments for public health protection and promotion in the UK

This is the final version of the article. Available from MDPI via the DOI in this record.Increasingly, the potential short and long-term impacts of climate change on human health and wellbeing are being demonstrated. However, other environmental change factors, particularly relating to the natural environment, need to be taken into account to understand the totality of these interactions and impacts. This paper provides an overview of ongoing research in the Health Protection Research Unit (HPRU) on Environmental Change and Health, particularly around the positive and negative effects of the natural environment on human health and well-being and primarily within a UK context. In addition to exploring the potential increasing risks to human health from water-borne and vector-borne diseases and from exposure to aeroallergens such as pollen, this paper also demonstrates the potential opportunities and co-benefits to human physical and mental health from interacting with the natural environment. The involvement of a Health and Environment Public Engagement (HEPE) group as a public forum of "critical friends" has proven useful for prioritising and exploring some of this research; such public involvement is essential to minimise public health risks and maximise the benefits which are identified from this research into environmental change and human health. Research gaps are identified and recommendations made for future research into the risks, benefits and potential opportunities of climate and other environmental change on human and planetary health.The research was funded in part by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London, and the Met Office (HPRU-2012-10016); the UK Medical Research Council (MRC) and UK Natural Environment Research Council (NERC) for the MEDMI Project (MR/K019341/1, https: //www.data-mashup.org.uk); the Economic and Social Research Council (ESRC) Project (ES/P011489/1); and the NIHR Knowledge Mobilisation Research Fellowship for Maguire

The effect of pond dyes on oviposition and survival in wild UK Culex mosquitoes

British Culex pipiens complex [Culex pipiens sensu lato) mosquito distribution, abundance, and potential for disease transmission are intimately linked to their environment. Pond and lake dyes that block light to restrict algal photosynthesis are a relatively new product assumed to be an environmentally friendly since they are based on food dyes. Their use in urban garden ponds raises questions linked to mosquito oviposition, since coloured water can be an attractant. Culex (mostly pipiens) is commonly found in UK gardens and is a potential vector of viruses including the West Nile Virus (WNV). Any factors that significantly change the distribution and population of Cx pipiens could impact future risks of disease transmission. A gravid trap was used to catch female Cx pipiens mosquitoes for use in oviposition choice tests in laboratory and semi-field conditions. Two types of pond dye, blue and shadow (which looks slightly red), were tested for their impact on oviposition and survival of wild caught Cx pipiens. There were no significant differences in the number of egg batches laid when gravid mosquitoes were given a choice between either blue dye and clear water or shadow dye and clear water indicating that these dyes are not attractants. Larvae hatched from egg batches laid by wild-caught gravid females were used to measure survival to adulthood with or without dye, , in a habitat controlled to prevent further colonisation. The experiment was run twice, once in the summer and again in the autumn, whereas the dyes had no impact on emergence in the summer, there were highly significant reductions in emergence of adults in both dye treated habitats in the autumn. Containers with or without shadow dye were placed outside to colonise naturally and were sampled weekly for larvae and pupae over a 6 month period through summer and autumn. There was a significant negative effect of shadow dye on pupal abundance in a three week period over the summer, but otherwise there was no effect. It is likely that population abundance and food was a more powerful factor for mosquito survival than the dye

Landscape structure affects the prevalence and distribution of a tick-borne zoonotic pathogen

Background Landscape structure can affect pathogen prevalence and persistence with consequences for human and animal health. Few studies have examined how reservoir host species traits may interact with landscape structure to alter pathogen communities and dynamics. Using a landscape of islands and mainland sites we investigated how natural landscape fragmentation affects the prevalence and persistence of the zoonotic tick-borne pathogen complex Borrelia burgdorferi(sensu lato), which causes Lyme borreliosis. We hypothesized that the prevalence of B. burgdorferi (s.l.) would be lower on islands compared to the mainland and B. afzelii, a small mammal specialist genospecies, would be more affected by isolation than bird-associated B. garinii and B. valaisiana and the generalist B. burgdorferi (sensu stricto). Methods Questing (host-seeking) nymphal I. Ricinus ticks (n = 6567) were collected from 12 island and 6 mainland sites in 2011, 2013 and 2015 and tested for B. burgdorferi(s.l.). Deer abundance was estimated using dung transects. Results The prevalence of B. burgdorferi (s.l.) was significantly higher on the mainland (2.5%, 47/1891) compared to island sites (0.9%, 44/4673) (P < 0.01). While all four genospecies of B. burgdorferi (s.l.) were detected on the mainland, bird-associated species B. garinii and B. valaisiana and the generalist genospecies B. burgdorferi(s.s.) predominated on islands. Conclusion We found that landscape structure influenced the prevalence of a zoonotic pathogen, with a lower prevalence detected among island sites compared to the mainland. This was mainly due to the significantly lower prevalence of small mammal-associated B. afzelii. Deer abundance was not related to pathogen prevalence, suggesting that the structure and dynamics of the reservoir host community underpins the observed prevalence patterns, with the higher mobility of bird hosts compared to small mammal hosts leading to a relative predominance of the bird-associated genospecies B. garinii and generalist genospecies B. burgdorferi (s.s.) on islands. In contrast, the lower prevalence of B. afzelii on islands may be due to small mammal populations there exhibiting lower densities, less immigration and stronger population fluctuations. This study suggests that landscape fragmentation can influence the prevalence of a zoonotic pathogen, dependent on the biology of the reservoir host

Are publicly available internet resources enabling women to make informed fertility preservation decisions before starting cancer treatment: an environmental scan?

Background To identify publicly available internet resources and assess their likelihood to support women making informed decisions about, and between, fertility preservation procedures before starting their cancer treatment. Methods A survey of publically available internet resources utilising an environmental scan method. Inclusion criteria were applied to hits from searches of three data sources (November 2015; repeated June 2017): Google (Chrome) for patient resources; repositories for clinical guidelines and projects; distribution email lists to contact patient decision aid experts. The Data Extraction Sheet applied to eligible resources elicited: resource characteristics; informed and shared decision making components; engagement health services. Results Four thousand eight hundred fifty one records were identified; 24 patient resources and 0 clinical guidelines met scan inclusion criteria. Most resources aimed to inform women with cancer about fertility preservation procedures and infertility treatment options, but not decision making between options. There was a lack of consistency about how health conditions, decision problems and treatment options were described, and resources were difficult to understand. Conclusions Unless developed as part of a patient decision aid project, resources did not include components to support proactively women’s fertility preservation decisions. Current guidelines help people deliver information relevant to treatment options within a single disease pathway; we identified five additional components for patient decision aid checklists to support more effectively people’s treatment decision making across health pathways, linking current with future health problems

Increased urinary trimethylamine N-oxide (TMAO) following Cryptosporidium infection and protein malnutrition independent of microbiome effects

Cryptosporidium infections have been associated with growth stunting, even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein-deficient mice were infected with Cryptosporidium parvum oocysts for 6–13 days and compared with uninfected controls. Following infection, there was an increase in the urinary excretion of choline- and amino-acid-derived metabolites. Conversely, infection reduced the excretion of the microbial–host cometabolite (3-hydroxyphenyl)propionate-sulfate and disrupted metabolites involved in the tricarboxylic acid (TCA) cycle. Correlation analysis of microbial and biochemical profiles resulted in associations between various microbiota members and TCA cycle metabolites, as well as some microbial-specific degradation products. However, no correlation was observed between the majority of the infection-associated metabolites and the fecal bacteria, suggesting that these biochemical perturbations are independent of concurrent changes in the relative abundance of members of the microbiota. We conclude that cryptosporidial infection in protein-deficient mice can mimic some metabolic changes seen in malnourished children and may help elucidate our understanding of long-term metabolic consequences of early childhood enteric infections

Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype

Background: Environmental enteropathy, linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is first understanding the effects of nutritional deficiencies on the mammalian system, including the effect on the gut microbiota. Objective: We dissect the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut microbiota changes that occur in weaned mouse models of zinc or protein deficiency as compared to well-nourished controls. Design: Using a 1H NMR spectroscopy-based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model. Results: We find considerable shifts within the intestinal microbiota 14-24d post-weaning in mice maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). While the zinc deficient microbiota were comparable to the age-matched well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14d post-weaning. We find that protein malnutrition impairs growth and has major metabolic consequences (much more than zinc deficiency) that include altered energy, polyamine and purine/pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed

Metabolic mechanisms of interaction within a defined gut microbiota

Metabolic interactions among species are ubiquitous in nature, and the fitness costs and benefits they impose often reinforce and stabilize them over time. These interactions are of particular importance in the human gut, where they have functions ranging from enhancing digestion to preventing (or exacerbating) infections. The diversity and sheer number of species present lead to the potential for a multitude of metabolic interactions among species to occur. However, identifying the mechanism and consequences of metabolic interactions between even two species is incredibly challenging. Here, we develop, apply, and experimentally test a framework for identifying potential metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from the altered Schaedler flora (ASF), a defined murine microbiota. We then apply our novel framework, which we call the Constant Yield Expectation (ConYE) model, to dissect emergent metabolic behaviors that occur in co-culture. Using the ConYE model, we identify and interrogate an amino acid cross-feeding interaction that is likely to confer a growth benefit to one ASF strain (Clostridium sp. ASF356) in co-culture with another strain (Parabacteroides goldsteinii ASF519). We experimentally validate that the proposed interaction leads to a growth benefit for this strain via media supplementation experiments. Our results reveal the type and extent of emergent metabolic behavior in microbial communities and demonstrate how metabolomic data can be used to identify potential metabolic interactions between organisms such as gut microbes. Our in vitro characterization of the ASF strains and interactions between them also enhances our ability to interpret and design experiments that utilize ASF-colonized animals. We anticipate that this work will improve the tractability of studies utilizing mice colonized with the ASF. Here, we focus on growth-modulating interactions, but the framework we develop can be applied to generate specific hypotheses about mechanisms of interspecies interaction involved in any phenotype of interest within a microbial community

Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli

Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens in malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we provide new insights into intersecting pathogen-specific mechanisms that enhance malnutrition. We show for the first time that during protein malnutrition, the intestinal microbiota permits persistent Giardia colonization and simultaneously contributes to growth impairment. Despite signals of intestinal injury, such as IL1α, Giardiainfected mice lack pro-inflammatory intestinal responses, similar to endemic pediatric Giardia infections. Rather, Giardia perturbs microbial host co-metabolites of proteolysis during growth impairment, whereas host nicotinamide utilization adaptations that correspond with growth recovery increase. EAEC promotes intestinal inflammation and markers of myeloid cell activation. During co-infection, intestinal inflammatory signaling and cellular recruitment responses to EAEC are preserved together with a Giardia-mediated diminishment in myeloid cell activation. Conversely, EAEC extinguishes markers of host energy expenditure regulatory responses to Giardia, as host metabolic adaptations appear exhausted. Integrating immunologic and metabolic profiles during co-pathogen infection and malnutrition, we develop a working mechanistic model of how cumulative diet-induced and pathogen-triggered microbial perturbations result in an increasingly wasted host