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Cecal metabolome fingerprint in a rat model of decompression sickness with neurological disorders

ABSTRACT: Massive bubble formation after diving can lead to decompression sickness (DCS), which can result in neurological disorders. We demonstrated that hydrogen production from intestinal fermentation could exacerbate DCS in rats fed with a standard diet. The aim of this study is to identify a fecal metabolomic signature that may result from the effects of a provocative hyperbaric exposure. The fecal metabolome was studied in two groups of rats previously fed with maize or soy in order to account for diet effects. 64 animals, weighing 379.0_20.2 g on the day of the dive, were exposed to the hyperbaric protocol. The rats were separated into two groups: 32 fed with maize (Div MAIZE) and 32 fed with soy (Div SOY). Gut fermentation before the dive was estimated by measuring exhaled hydrogen. Following hyperbaric exposure, we assessed for signs of DCS. Blood was analyzed to assay inflammatory cytokines. Conventional and ChemRICH approaches helped the metabolomic interpretation of the cecal content. The effect of the diet is very marked at the metabolomic level, a little less in the blood tests, without this appearing strictly in the clinic status. Nevertheless, 37 of the 184 metabolites analyzed are linked to clinical status. 35 over-expressed compounds let suggest less intestinal absorption, possibly accompanied by an alteration of the gut microbial community, in DCS. The decrease in another metabolite suggests hepatic impairment. This spectral difference of the ceca metabolomes deserves to be studied in order to check if it corresponds to functional microbial particularities.

SUBMITTER: de Maistre S

PROVIDER: S-EPMC7524739 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:Decompression sickness (DCS) is a potentially fatal condition usually observed after scuba diving. It involves bubble formation in blood and tissues from dissolved inert gas (usually nitrogen or helium), secondary to decreases in ambient pressure (decompression).To the best of our knowledge, no study has evaluated a DCS-induced transcriptomic signature in humans. In this study, we aim to explore the evolution of leukocyte gene expression in human subjects with DCS compared to closely matched divers after uneventful diving using a hypothesis-free RNA sequencing approach .Recruitment of DCS cases (n = 7) and controls (n = 6) was carried out using specific criteria. For both DCS cases and controls, whole blood was sampled at two time points, T1 - within 8 hours of surfacing from diving and T2 - at 40-44 hours after surfacing. Prior to sampling at T2, subjects were fasted for 10 hours. Specific exclusion criteria included a) age < 18 years b) self-reported consumption of alcohol and/or strenuous physical activity before T2 c) symptoms suggestive of delayed DCS presentation in controls at T2 d) acute life-threatening clinical complications or death within 72 hours of surfacing. All cases received emergency HBO as per United States Navy Treatment Table Six between T1 and T2.For RNA isolation, 2.5mL of whole blood was collected in a PAXgene® Blood RNA Tube (PreAnalytiX, Qiagen/BD) from DCS cases and controls at both T1 and T2. The quality of RNA was evaluated by RNA Integrity Number (RIN) determination using the RNA6000 Nano protocol on an Agilent 2100 Bioanalyzer system (Agilent, USA). The RIN values for samples undergoing transcriptome analysis ranged from 7.8 to 9.3. Depletion of alpha and beta globin mRNA was carried out using the GLOBINclear™ kit (ThermoFisher Scientific). To minimize batch effects, all samples were processed simultaneously by the same investigator. RNA samples were submitted for library generation and sequencing by the Beijing Genomics Institute (BGI-Shenzhen). Briefly, poly(A) mRNA was enriched using poly(T) oligo-attached magnetic beads, followed by fragmentation. First strand cDNA synthesis was carried out using random hexamer N6 primers and reverse transcriptase. Following adaptor ligation to cDNA fragments, PCR amplification and purification, single stranded DNA circles were generated in a final library. DNA nanoballs (DNBs) were subsequently generated by rolling circle replication, which underwent paired end sequencing (100bp) on the BGI DNBseq platform.

Project description:BACKGROUND:The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-h survival in a rat sepsis model. METHODS:Adult male Sprague-Dawley rats (375-425?g) were subjected to 35% cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/h) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/h). Resuscitation under general anesthesia proceeded for the next 6 h (t?=?22?h to t?=?28?h); lactate was checked every 2?h, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisher exact test was used to analyze the primary outcome of 48-h survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but preresuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared with sham animals. FFP significantly increased 48-h survival compared to NS (n?=?8 [57%] vs n?=?2 [14%]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/mL), norepinephrine, (3.8 vs 8.9?ng/mL), IL-6 (3.8 vs 18.7?ng/mL), and syndecan-1 (21.8 vs 31.0?ng/mL) (all P?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all P?<?0.05). CONCLUSION:Compared to crystalloid, plasma resuscitation increased 48-h survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

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Cecal metabolome fingerprint in a rat model of decompression sickness with neurological disorders

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