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Evidence of a hormonal reshuffle in the cecal metabolome fingerprint of a strain of rats resistant to decompression sickness.

ABSTRACT: On one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the fecal metabolome from rat caecum. On the other side, there is high inter-individual variability in terms of occurrence of DCS. One could wonder whether the fecal metabolome could be linked to the DCS-susceptibility. We decided to study male and female rats selected for their resistance to decompression sickness, and we hypothesize a strong impregnation concerning the fecal metabolome. The aim is to verify whether the rats resistant to the accident have a fecal metabolomic signature different from the stem generations sensitive to DCS. 39 DCS-resistant animals (21 females and 18 males), aged 14 weeks, were compared to 18 age-matched standard Wistar rats (10 females and 8 males), i.e., the same as those we used for the founding stock. Conventional and ChemRICH approaches helped the metabolomic interpretation of the 226 chemical compounds analyzed in the cecal content. Statistical analysis shows a panel of 81 compounds whose expression had changed following the selection of rats based on their resistance to DCS. 63 compounds are sex related. 39 are in common. This study shows the spectral fingerprint of the fecal metabolome from the caecum of a strain of rats resistant to decompression sickness. This study also confirms a difference linked to sex in the metabolome of non-selected rats, which disappear with selective breeding. Results suggest hormonal and energetic reshuffle, including steroids sugars or antibiotic compounds, whether in the host or in the microbial community.

SUBMITTER: Vallee N

PROVIDER: S-EPMC8050073 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMost cases of decompression sickness (DCS) occur soon after surfacing, with 98% within 24 hours. Recompression using hyperbaric chamber should be administrated as soon as feasible in order to decrease bubble size and avoid further tissue injury. Unfortunately, there may be a significant time delay from surfacing to recompression. The time beyond which hyperbaric treatment is non effective is unclear. The aims of the study were first to evaluate the effect of delayed hyperbaric treatment, initiated more than 48 h after surfacing for DCS and second, to evaluate the different treatment protocols.MethodsFrom January 2000 to February 2014, 76 divers had delayed hyperbaric treatment (≥48 h) for DCS in the Sagol center for Hyperbaric medicine and Research, Assaf-Harofeh Medical Center, Israel. Data were collected from their medical records and compared to data of 128 patients treated earlier than 48 h after surfacing at the same hyperbaric institute.ResultsThere was no significant difference, as to any of the baseline characteristics, between the delayed and early treatment groups. With respect to treatment results, at the delayed treatment divers, complete recovery was achieved in 76% of the divers, partial recovery in 17.1% and no improvement in 6.6%. Similar results were achieved when treatment started early, where 78% of the divers had complete recovery, 15.6% partial recovery and 6.2% no recovery. Delayed hyperbaric treatment using US Navy Table 6 protocol trended toward a better clinical outcome yet not statistically significant (OR=2.786, CI95%[0.896-8.66], p=0.07) compared to standard hyperbaric oxygen therapy of 90 minutes at 2 ATA, irrespective of the symptoms severity at presentation.ConclusionsLate recompression for DCS, 48 hours or more after surfacing, has clinical value and when applied can achieve complete recovery in 76% of the divers. It seems that the preferred hyperbaric treatment protocol should be based on US Navy Table 6.

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.

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Evidence of a hormonal reshuffle in the cecal metabolome fingerprint of a strain of rats resistant to decompression sickness.

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