Biology subjects

Dennis, P. G.

Publications and source records attributed to Dennis, P. G..

6 recordsLinked to original sources

bioRxiv2024

A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling

Poor maternal diet during pregnancy predisposes to severe lower respiratory tract infections (sLRI) in infancy, which in turn, increases childhood asthma risk, however the underlying mechanisms remain poorly understood. Here, we show that the offspring of high fat diet (HFD)-fed mothers ( HFD-reared pups) developed a sLRI following pneumovirus inoculation in early-life and subsequent asthma in later-life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyper-granulopoiesis in the liver and elevated inflammatory cytokine expression, most notably IL-17A, IL-6 and sIL-6R (indicative of IL-6 trans-signaling) in the circulation and multiple organs, but most prominently the liver. Inhibition of IL-6 trans-signaling, using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils, conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

immunology↗

bioRxiv2023

Fecal microbial transfer and complex carbohydrates mediate protection against COPD

ObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DesignUsing an in vivo mouse model of cigarette smoke-induced COPD and fecal microbial transfer (FMT), we characterized the fecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology, and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in sixteen COPD patients using a randomized, double-blind, placebo-controlled pilot study of inulin supplementation. ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in cigarette smoke-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically. What is already known on this topicO_LIChanges in gut microbiota are associated with COPD but the underlying host and microbial mechanisms are unclear, limiting the therapeutic applications. C_LI What this study addsO_LIMicrobiome composition and metabolism is reproducibly correlated with lung and gastrointestinal pathology in experimental COPD. C_LIO_LIMicrobiome modifying interventions effectively alleviate disease, including protective effects supplementing smoking cessation. C_LIO_LINutritional interventions targeting the microbiome in COPD patients demonstrate efficacy in a small pilot study. C_LI How this study might affect research, practice or policyO_LIMicrobiome-targeting therapeutics and nutritional interventions may be developed for COPD, including as supplements to smoking cessation. C_LI

physiology↗

bioRxiv2023

The maternal microbiome regulates infant respiratory disease susceptibility via intestinal Flt3L expression and plasmacytoid dendritic cell hematopoiesis

Severe lower respiratory infection (sLRI) are a major cause of infant morbidity and mortality, and predispose to later chronic respiratory diseases such as asthma. Poor maternal diet during pregnancy is a risk factor for sLRI in the offspring. Here we demonstrate in mice that a maternal low-fibre diet (LFD) disrupts plasmacytoid and conventional dendritic cell (DC) hematopoiesis in the offspring, predisposing to sLRI and subsequent asthma. The LFD alters the composition of the maternal milk microbiome and assembling infant gut microbiome, ablating the induction of a developmental wave of the non-redundant DC growth factor Flt3L by neonatal intestinal epithelial cells. Therapy with a propionate-producing bacteria isolated from the milk of high-fibre diet-fed mothers, or supplementation with propionate, confers protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that regulates pDC hematopoiesis in early life and confers disease resistance. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=51 SRC="FIGDIR/small/522516v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1a39990org.highwire.dtl.DTLVardef@1b6fe67org.highwire.dtl.DTLVardef@f8440dorg.highwire.dtl.DTLVardef@13bc67e_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2019

Soil chloride content influences the response of bacterial but not fungal diversity to silver nanoparticles entering soil via wastewater treatment processing

Silver nanoparticles (NPs) are among the most widely used nanomaterials and are entering soil ecosystems, mainly via biosolids in agriculture. When added directly to soils, metallic Ag-NPs have been shown to affect microbial communities, which underpin important ecosystem functions. During wastewater treatment processing, metallic Ag-NPs are rapidly converted to Ag2S, which is relatively insoluble and less toxic. Furthermore, recent evidence indicates that silver bioavailability is influenced by soil chloride content. Hence there is a need to understand the impacts of wastewater treatment processed Ag-NPs at varying levels of salinity on soil microbial diversity. In this study, we examined how the application of 0 g, 1 g and 2 g kg-1 NaCl to soil influence the effects of 0 mg, 1 mg and 10 mg kg-1 Ag, applied as wastewater treatment processed Ag-NPs, on bacterial and fungal diversity over time. Using high-throughput phylogenetic marker gene sequencing we demonstrate that, despite being theoretically less toxic, wastewater treatment processed Ag-NPs can affect the composition of soil bacterial and fungal communities, and influence bacterial alpha diversity. In addition, we found that silver-associated changes in bacterial community composition were affected by soil chloride content, with more acute responses to silver being observed in more saline soils. This work highlights that the release of Ag-NPs into soils via realistic exposure pathways can alter microbial diversity and that these effects may be influenced by soil chloride content.\n\nSummary capsuleSoil chloride content influences the response of bacterial but not fungal diversity to wastewater treatment processed silver nanoparticles.

microbiology↗

bioRxiv2019

Effects of carbon nanotubes and derivatives of graphene oxide on soil bacterial diversity

Carbon nanotubes (CNTs), reduced graphene oxide (rGO) and ammonia-functionalized graphene oxide (aGO), are nanomaterials that possess varied and useful properties. However, following their use, their release into the environment is inevitable. While CNTs have been shown to influence soil bacterial diversity, albeit at very high concentration, the effects of rGO have only been examined using pure bacterial cultures, and those of aGO are unknown. Here, we investigated the effects of CNTs, rGO and aGO, at three time points (7, 14 and 30 days), and over a range of concentrations (1 ng, 1 {micro}g and 1 mg kg dry soil-1), on soil bacterial diversity using 16S rRNA amplicon sequencing. Graphite was included to facilitate comparisons with a similar and naturally occurring carbon material, while the inclusion of GO allowed the effects of GO modification to be isolated. Bacterial community composition, but not alpha diversity, was altered by all treatments except the low GO, low rGO and high aGO treatments on day 14 only. In all cases, the nanomaterials led to shifts in community composition that were of similar magnitude to those induced by graphite and GO, albeit with differences in the taxa affected. Our study highlights that nanocarbon materials can induce changes in soil bacterial diversity, even at doses that are environmentally realistic.

microbiology↗

bioRxiv2019

Graphene oxide affects soil bacterial and fungal diversity even at parts-per-trillion concentrations

Graphene oxide (GO) is an oxidized form of graphene that is relatively cheap and easy to produce. This has heralded its widespread use in a range of industries, with its likelihood of release into the environment increasing accordingly. In pure culture, GO has been shown to influence bacteria and fungi, but its effects on environmental microbial communities remain poorly characterized, despite the important ecosystem services that these organisms underpin. Here, we characterized the effects of GO and graphite, over time and at three concentrations (1 ng, 1 {micro}g and 1 mg kg dry soil-1), on soil bacterial and fungal diversity using 16S rRNA and ITS2 gene amplicon sequencing. Graphite was included as a reference material as it is widely distributed in the environment. Neither GO or graphite had significant effects on the alpha diversity of microbial communities. The composition of bacterial and fungal communities, however, was significantly influenced by GO and graphite. These effects were equally apparent between doses and varied over time. Predicted KEGG pathways and fungal guild structures were not significantly influenced by the treatments. Our study demonstrates that GO can influence soil microbial diversity, even at parts-per-trillion concentration, which is equivalent to the rates of release predicted for similar nanomaterials such as carbon nanotubes. ImportanceGraphene oxide is a nanomaterial with broad and expanding industrial applications. Some evidence indicates that it can influence the growth of microorganisms, many of which support important ecosystem services, such as the provision of food and clean water. The amount of graphene oxide currently entering soils is not known but is likely to be similar to other nanomaterials, such as carbon nanotubes (i.e. parts-per-trillion to parts-per-billion per year). In this study, we demonstrate that graphene oxide added to soil at these concentrations (or higher) can alter the composition of bacterial and fungal communities. Nonetheless, we found that these changes were of similar magnitude to those associated with the addition of graphite, which is common and occurs naturally in soils. Further research is recommended to determine whether the changes in microbial community composition that we have shown can be induced by graphene oxide, have deleterious consequences for soil health.

microbiology↗