Summary of Study ST003536

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002176. The data can be accessed directly via it's Project DOI: 10.21228/M8BV78 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003536
Study TitleProbiotics and their metabolite spermidine enhance IFN-γ+CD4+ T cell immunity to inhibit hepatitis B virus
Study SummaryThe therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as HBsAg loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic IFN-γ+CD4+ T cell immune response. Depletion of CD4+ T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in gut and transports to liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ+CD4+ T cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and theirs derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ+CD4+ T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.
Institute
Shandong University
Last NameWang
First NameTixiao
Address44 Wenhua Xi Road, Jinan, Shandong
Emailtixwang@163.com
Phone18560082747
Submit Date2024-10-10
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailLC-MS
Release Date2024-11-15
Release Version1
Tixiao Wang Tixiao Wang
https://dx.doi.org/10.21228/M8BV78
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002176
Project DOI:doi: 10.21228/M8BV78
Project Title:Metabolomics data of feces from Control and BLE mice
Project Summary:Untargeted metabolomic analysis showed that 38 metabolites were significantly different between control and BLE mice. Among them, oligosaccharides (1-kestose, raffinose, maltotriose), amino acids (N-Acetyl-L-leucine, glutamic acid) and polyamine (spermidine, SPD) were the most varied enriched metabolites.
Institute:Shandong University
Last Name:Wang
First Name:Tixiao
Address:44# Wenhua Xi Road, Jinan, Shandong Province, 250012, China
Email:tixwang@163.com
Phone:18560082747

Subject:

Subject ID:SU003665
Subject Type:Other organism
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male

Factors:

Subject type: Other organism; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Treatment
SA387535B2Feces BLE
SA387536B10Feces BLE
SA387537B9Feces BLE
SA387538B8Feces BLE
SA387539B7Feces BLE
SA387540B6Feces BLE
SA387541B5Feces BLE
SA387542B4Feces BLE
SA387543B1Feces BLE
SA387544C3Feces Control
SA387545C10Feces Control
SA387546C9Feces Control
SA387547C8Feces Control
SA387548C7Feces Control
SA387549C6Feces Control
SA387550C5Feces Control
SA387551C4Feces Control
SA387552C2Feces Control
Showing results 1 to 18 of 18

Collection:

Collection ID:CO003658
Collection Summary:Male five-week-old C57BL/6J mice were hydrodynamically injected with 6 μg of AAV/HBV1.2 plasmid and gavage fed with probiotics (BLE, PBS as control) daily starting at 3 day post of hydrodynamically injection. Feces collected from Control and BLE mice after 6 weeks.
Sample Type:Feces

Treatment:

Treatment ID:TR003674
Treatment Summary:Male five-week-old C57BL/6J mice were hydrodynamically injected with 6 μg of AAV/HBV1.2 plasmid and gavage fed with probiotics (BLEl) daily at 3 dpi of hydrodynamically injection.

Sample Preparation:

Sampleprep ID:SP003672
Sampleprep Summary:Take 50±1mg sample into the 2mL EP tubes, extracted with 0.3mL extraction liquid (VMethanol: VChlorofrom = 3:1), add 20μL of L-2-Chlorophenylalanine (1mg/mL stock in dH2O) as internal standard, vortex mixing for 30s; Homogenized in ball mill for 4min at 45Hz, then ultrasound treated for 5min (incubated in ice water); Centrifuge for 15min at 12000rpm, 4℃; Transfer the supernatant (0.2mL) into a fresh 2mL GC/MS glass vial , take 30μL from each sample and pooling as QC sample. Dry completely in a vacuum concentrator without heating; Add 30μL Methoxy amination hydrochloride (20mg/mL in pyridine) incubated for 30min at 80℃; Add 40μL of the BSTFA regent (1% TMCS, v/v) to the sample aliquots, incubated for 1.5h at 70℃; Add 5μL FAMEs (Standard mixture of fatty acid methyl esters, C8-C16:1mg/mL; C18-C24:0.5mg/mL in chloroform) to the QC sample when cooling to the room temperature; All samples were analyzed by gas chromatograph system coupled with a Pegasus HT time-of-flight mass spectrometer (GC-TOF-MS).

Combined analysis:

Analysis ID AN005808
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890B
Column Agilent DB5-MS (30m x 0.25mm, 0.25um)
MS Type ESI
MS instrument type GC-TOF
MS instrument name Agilent 7890B
Ion Mode UNSPECIFIED
Units peak area

Chromatography:

Chromatography ID:CH004411
Chromatography Summary:GC-TOF-MS analysis was performed using an Agilent 7890 gas chromatograph system coupled with a Pegasus HT time-of-flight mass spectrometer. The system utilized a DB-5MS capillary column coated with 5% diphenyl cross-linked with 95% dimethylpolysiloxane (30m×250μm inner diameter, 0.25μm film thickness; J&W Scientific, Folsom, CA, USA). A 1μL aliquot of the analyte was injected in splitless mode. Helium was used as the carrier gas, the front inlet purge flow was 3mL min−1, and the gas flow rate through the column was 1mL min−1. The initial temperature was kept at 50°C for 1min, then raised to 310°C at a rate of 10°C min−1, then kept for 8min at 310°C. The injection, transfer line, and ion source temperatures were 280, 280, and 250°C, respectively. The energy was -70eV in electron impact mode. The mass spectrometry data were acquired in full-scan mode with the m/z range of 50-500 at a rate of 20 spectra per second after a solvent delay of 6.27min.
Instrument Name:Agilent 7890B
Column Name:Agilent DB5-MS (30m x 0.25mm, 0.25um)
Column Temperature:50°C
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:GC

MS:

MS ID:MS005528
Analysis ID:AN005808
Instrument Name:Agilent 7890B
Instrument Type:GC-TOF
MS Type:ESI
MS Comments:Chroma TOF 4.3X software of LECO Corporation and LECO-Fiehn Rtx5 database were used for raw peaks exacting, the data baselines filtering and calibration of the baseline, peak alignment, deconvolution analysis, peak identification and integration of the peak area1. Both of mass spectrum match and retention index match were considered in metabolites identification. Remove peaks detected in <50% of QC samples or RSD>30% in QC samples.
Ion Mode:UNSPECIFIED
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