Dataset Information

Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury.

ABSTRACT:

Background

Non-severe paediatric burns can result in poor long-term health outcomes. This occurs even in cases with good acute burn-related outcomes, including minimal scarring. The mechanisms that underpin the transition from non-severe burn to sustained negative long-term health impacts are currently unknown. However, sustained metabolic and immune changes have been observed in paediatric burn studies, suggesting these changes may be important.The plasma lipidome consists of a rich pool of bioactive metabolites that play critical roles in systemic processes including molecular signalling and inflammation. We hypothesised that changes in the plasma lipidome may reflect underlying changes in health status and be linked to long-term health after burn trauma.

Methods

This study analysed the lipidome in children who had previously experienced a non-severe burn, compared to non-injured controls. Thirty-three participants were recruited between the ages of 5 and 8 years who had experienced a non-severe burn between the ages of 1 and 3 years. Plasma samples were also collected from a non-injured, healthy, age and gender matched control group (n = 21). Plasma lipids were measured using reversed-phase liquid chromatographymass spectrometery (LC-MS).

Results

In total 838 reproducible lipid species from 19 sub-classes passed quality control procedures and progressed to statistical analysis. Analysis of individual lipid metabolites showed significantly higher concentrations of lysophosphatidylethanolamines and phosphatidylethanolamines, and significantly lower concentrations in myristic, palmitic and palmitoleic acids in the plasma of those who had experienced burn injury compared to controls.

Conclusion

Long-term changes in the lipid profile may give insight into the mechanisms underlying poor long-term health subsequent to non-severe burn injury. Further work to investigate the relationship between long-term pathology and lipidomic changes may lead to a better understanding of the causes of secondary morbidity post-burn and to clinical intervention to reduce the long-term health burden of burn trauma.

SUBMITTER: Kierath E

PROVIDER: S-EPMC10703495 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury.

Kierath Eva E Ryan Monique M Holmes Elaine E Nicholson Jeremy K JK Fear Mark W MW Wood Fiona M FM Whiley Luke L Gray Nicola N

Burns & trauma 20231207

<h4>Background</h4>Non-severe paediatric burns can result in poor long-term health outcomes. This occurs even in cases with good acute burn-related outcomes, including minimal scarring. The mechanisms that underpin the transition from non-severe burn to sustained negative long-term health impacts are currently unknown. However, sustained metabolic and immune changes have been observed in paediatric burn studies, suggesting these changes may be important.The plasma lipidome consists of a rich poo ...[more]

PMID: 38074192

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Project description:Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of a nonsevere burn injury, longitudinal plasma was collected from adults (n = 35) who presented at hospital with a nonsevere burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from nonburn control participants (n = 14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoprotein signatures and 852 lipid species from across 20 subclasses. Multivariate data modeling (orthogonal projections to latent structures-discriminate analysis; OPLS-DA) revealed alterations in lipoprotein and lipid metabolism when comparing the baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value < 1.0e-4), low density lipoprotein-2 subfractions (variable importance in projection score; VIP > 6.83e-1) and monoacyglyceride (20:4) (p-value < 1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP > 7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols, and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of a nonsevere burn injury. The phenotype is indicative of an acute inflammatory profile that continues to be sustained postinjury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have an elevated incidence postburn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalize intervention strategies, and improve acute care, reducing the risk of chronic comorbidity.

Project description:Burn injury is associated with a loss of gut barrier function, resulting in systemic dissemination of gut-derived bacteria and their products. The bacterial protein and TLR5 agonist, flagellin, induces non-specific innate immune responses. Because we detected flagellin in the serum of burn patients, we investigated whether gut-derived flagellin was a primary or secondary contributor to intestinal dysfunction and systemic inflammation following burn injury. The apical surface of polarized human intestinal epithelial cells (IECs), Caco-2BBe, were exposed to 50 or 500 ng of purified flagellin and 1 x 105 of an intestinal E. coli (EC) isolate as follows: 1) flagellin added 30 min prior to EC, 2) flagellin and EC added simultaneously, or 3) EC added 30 min prior to flagellin. Our results showed that luminal flagellin and EC modulated each other's biological actions, which influenced their ability to induce basolateral secretion of inflammatory cytokines and subsequent translocation of bacteria and their products. A low dose of flagellin accompanied by an enteric EC in the lumen, tempered inflammation in a dose- and time-dependent manner. However, higher doses of flagellin acted synergistically with EC to induce both intestinal and systemic inflammation that compromised barrier integrity, increasing systemic inflammation following burn injury, a process we have termed flagellemia. In a murine model of burn injury we found that oral gavage of flagellin (1 μg/mouse) significantly affected the gut microbiome after burn injury. In these mice, flagellin disseminated out of the intestine into the serum and to distal organs (mesenteric lymph nodes and lungs) where it induced secretion of monocyte chemoattractant protein (MCP-1) and CXCL1/KC (mouse equivalent of human IL-8) at 24 and 48h post-burn. Our results illustrated that gut-derived flagellin alone or accompanied by a non-pathogenic enteric EC strain can function as an initiator of luminal and systemic inflammation following burn injury.

Project description:Abstract Background Survivors of childhood bacterial meningitis (BM) from low-income countries are at increased risk of sequelae. How BM survivors’ daily life is affected in the developing world, is not known. We aimed to investigate the quality of life among pediatric survivors of BM in Luanda, Angola assessing both physical and psychosocial health-related quality of life (HRQOL). Methods Survivors from two BM treatment trials (ISRCTN62824827; NCT01540838) from Luanda Children’s Hospital were called to follow-up visits in January 2017 with a median duration of 26 months after BM. We administered Pediatric Quality of Life InventoryTM (PedsQLTM) 4.0 Generic Core Scales and Infant Scales, designed to measure HRQOL in children, to patients and/or parents. The generic core scales were administered to 64 and 32 families, and the infant scores to 8 and 3 care-givers of patients and controls, respectively. We used age-appropriate versions of the scales. We calculated the total, physical and psychosocial HRQOL domains. To determine internal consistency, Cronbach’s alpha coefficients were calculated for generic score scales. Results In all, 73 survivors of BM and 36 control children participated. 18 (51%) of controls were siblings of survivors; others visited the hospital for vaccinations. The median age of children was 6 years (81 months, IQR 85 months). Survivors of BM scored significantly lower on the PedsQLTM 4.0 generic core and infant scales than control children according to parent proxy reports indicating lower HRQOL (total score 81.04 vs. 91.30, P = 0.001; physical health 87.50 vs. 100.00, P = 0.0002; psychosocial health 79.06 vs. 90.00, P = 0.001). Child self-report scores were also lower within BM survivors who were able to answer; however, the difference was not statistically significant. In total sample of survivors, the Cronbach’s alphas reached sufficient reliability of 0.70 in all three domains calculated (total score, ?=0.79; physical health ?= 0.77; psychosocial health ?= 0.89 for child self-reports and ?=0.91, ?=0.91, and ?=0.84 for parent proxy-reports, respectively). Conclusion The survivors of pediatric BM endure a clearly suboptimal quality of life compared with siblings and other control children. HRQOL can be measured reliably among BM patients in developing country setting. Disclosures All authors: No reported disclosures.

Dataset Information

Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury.

Background

Methods

Results

Conclusion

Publications

Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury.

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