GeneSet Information

Tier IV GS409775 • Differentially expressed genes in mouse ileum without microbiome + morphine treatment (AM group) vs morphine only_qvalue

DESCRIPTION:

Small intestine transcriptome changes in morphine treated mice without microbiome (Abx+morphine (AM)) (n = 7) vs morphine treated mice (n = 5). Eight-week-old, pathogen free, C57BL/6 male mice were used for this study. For depletion of the gut microbiota, a pan-antibiotics+antifungal cocktail [vancomycin 32 (mg/kg), bacitracin (80mg/kg), metronidazole (80mg/kg), neomycin (320mg/kg), and pimaricin (0.192mg/kg)] was prepared every day in drinking water. The cocktail was administered by oral gavage for 7 days as described previously. The animals were anesthetized using isoflurane (Pivetal®) and a 25mg slow-release morphine pellet or placebo pellet was implanted subcutaneously. Treatment lasted 16 hours. mRNA was purified from total RNA from using poly T-magnetic beads and strand specific library was constructed by using NEBNext Ultra RNA library prep kit. After quality control, the libraries were sequenced paired end by using Illumina sequencers (Illumina NovaSeq 6000) for a read length of 150 base pairs. Clean reads were mapped to the mouse transcriptome using “STAR” software. The subsequent differential gene expression analysis was performed using DESeq2 R package (log2 (Fold change) > 1, P adj<0.05).

LABEL:

DEG mouse ileum AM group vs morphine_qvalue

SCORE TYPE:

Q-Value

THRESHOLD:

<= 0.05

GENES IN THRESHOLD:

1361

DATE ADDED:

2024-12-20

DATE UPDATED:

2024-12-20

SPECIES:

AUTHORS:

Udhghatri Kolli, Richa Jalodia, Shamsudheen Moidunny, Praveen Kumar Singh, Yuguang Ban, Junyi Tao, Gonzalo Nathaniel Cantu, Eridania Valdes, Sundaram Ramakrishnan, Sabita Roy

TITLE:

Multi-omics analysis revealing the interplay between gut microbiome and the host following opioid use.

JOURNAL:

Gut microbes Dec 2023, Vol 15, pp. 2246184

ABSTRACT:

Opioid crisis is an ongoing epidemic since the past several decades in the United States. Opioid use-associated microbial dysbiosis is emerging as a key regulator of intestinal homeostasis and behavioral responses to opioid. However, the mechanistic insight into the role of microbial community in modulating host response is unavailable. To uncover the role of opioid-induced dysbiosis in disrupting intestinal homeostasis we utilized whole genome sequencing, untargeted metabolomics, and mRNA sequencing to identify changes in microbiome, metabolome, and host transcriptome respectively. Morphine treatment resulted in significant expansion of Parasuterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and depletion of Lactobacillus johnsonii. These changes correlated with alterations in lipid metabolites and flavonoids. Significant alteration in microbial metabolism (metabolism of lipids, amino acids, vitamins and cofactors) and increased expression of virulence factors and biosynthesis of lipopolysaccharides (LPS) and lipoteichoic acid (LTA) were observed in microbiome of morphine-treated animals. In concurrence with changes in microbiome and metabolome extensive changes in innate and adaptive immune response, lipid metabolism, and gut barrier dysfunction were observed in the host transcriptome. Microbiome depleted mice displayed lower levels of inflammation, immune response and tissue destruction compared to mice harboring a dysbiotic microbiome in response to morphine treatment, thus establishing dysbiotic microbiome as mediator of morphine gut pathophysiology. Integrative analysis of multi-omics data highlighted the associations between Parasutterella excrementihominis, Burkholderiales bacterium 1_1_47, Enterococcus faecalis, Enterorhabdus caecimuris and altered levels of riboflavin, flavonoids, and lipid metabolites including phosphocholines, carnitines, bile acids, and ethanolamines with host gene expression changes involved in inflammation and barrier integrity of intestine. Omic analysis also highlighted the role of probiotic bacteria Lactobacillus johnsonii, metabolites flavonoids and riboflavin that were depleted with morphine as important factors for intestinal homeostasis. This study presents for the first time ever an interactive view of morphine-induced changes in microbial metabolism, strain level gut microbiome analysis and comprehensive view of changes in gut transcriptome. We also identified areas of potential therapeutic interventions to limit microbial dysbiosis and present a unique resource to the opioid research community. PUBMED: 37610102
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Annotation Information

No sequence read archive data associated with this GeneSet.


Vancomycin (D014640)
Homeostasis (D006706)
United States (D014481)
Metabolomics (D055432)
Drinking (D004326)
Acids (D000143)
Probiotics (D019936)
Animals (D000818)
RNA (D012313)
Libraries (D007990)
Magnetics (D008280)
Lipopolysaccharides (D008070)
Bacteria (D001419)
Bacitracin (D001414)
Immunity (D007109)
Genome (D016678)
Metabolome (D055442)
Mice (D051379)
Gene Expression Profiling (D020869)
Software (D012984)
Poly T (D011071)
Isoflurane (D007530)
Gene Expression (D015870)
RNA, Messenger (D012333)
Base Pairing (D020029)
Water (D014867)
Therapeutics (D013812)
Role (D012380)
Intestine, Small (D007421)
Intestines (D007422)
Ethanolamines (D004983)
Health Resources (D006295)
Time (D013995)
Vitamins (D014815)
Flavonoids (D005419)
Residence Characteristics (D012111)
Tissues (D014024)
Riboflavin (D012256)
Genes (D005796)
Inflammation (D007249)
Natamycin (D010866)
Bile (D001646)
Bile Acids and Salts (D001647)
Neomycin (D009355)
Enterococcus faecalis (D013293)
Amino Acids (D000596)
Anti-Bacterial Agents (D000900)
Virulence (D014774)
Lactobacillus (D007778)
Morphine (D009020)
Quality Control (D011786)
Metronidazole (D008795)
Lipid Metabolism (D050356)
Lipids (D008055)
Sprains and Strains (D013180)
Virulence Factors (D037521)
Association (D001244)
Research (D012106)
Metabolism (D008660)
Adaptive Immunity (D056704)
Analgesics, Opioid (D000701)
Enterococcus (D016983)
small intestine (MA:0000337)
intestine (MA:0000328)
gut (MA:0000917)
bile (MA:0002513)
abnormal inflammatory response (MP:0001845)
lipid metabolic process (GO:0006629)
stem cell factor receptor activity (GO:0005020)
metabolic process (GO:0008152)
response to morphine (GO:0043278)
adaptive immune response (GO:0002250)
homeostatic process (GO:0042592)
biosynthetic process (GO:0009058)
pathogenesis (GO:0009405)
inflammatory response (GO:0006954)
immune response (GO:0006955)
viral reproduction (GO:0016032)
proteasome-activating nucleotidase complex (GO:0022623)
gene expression (GO:0010467)
RNA (EDAM_topic:0099)
Gene expression analysis (EDAM_operation:2410)
Metabolomics (EDAM_topic:3172)
Analysis (EDAM_operation:2945)
Evaluation and validation (EDAM_operation:2428)
Sequencing (EDAM_topic:3168)
Transcriptomics (EDAM_topic:0203)
Lipids (EDAM_topic:0153)
Small molecules (EDAM_topic:0154)
Data (EDAM_data:0006)
Metabolites (EDAM_topic:0079)
Gene expression data processing (EDAM_operation:2495)
Differential expression analysis (EDAM_operation:3223)
rna (EDAM_format:1213)
nucleobase (CHEBI:18282)
vitamin (CHEBI:33229)
morphine (CHEBI:17303)
poly(acrylonitrile) polymer (CHEBI:61639)
lipoteichoic acid (CHEBI:28640)
virulence factor (CHEBI:72316)
Natamycin (CHEBI:7488)
water (CHEBI:15377)
maleate(2-) (CHEBI:30780)
base (CHEBI:22695)
lipid (CHEBI:18059)
antifungal agent (CHEBI:35718)
Leu-Thr-Ala (CHEBI:73572)
metronidazole (CHEBI:6909)
acid (CHEBI:37527)
vancomycin (CHEBI:28001)
flavonoids (CHEBI:72544)
lipopolysaccharide (CHEBI:16412)
bile acid (CHEBI:3098)
phosphocholines (CHEBI:36700)
poly(deoxythymidylic acid) (CHEBI:73300)
vancomycin(1+) (CHEBI:76842)
poly(acrylonitrile) macromolecule (CHEBI:53571)
primary amino group (CHEBI:46882)
ribonucleic acid (CHEBI:33697)
messenger RNA (CHEBI:33699)
riboflavin (CHEBI:17015)
role (CHEBI:50906)
bacitracin (CHEBI:28669)
1-acyl-sn-glycero-3-phosphoserine (CHEBI:52603)
ethanolamines (CHEBI:23981)
LPS with O-antigen (CHEBI:89981)
metabolite (CHEBI:25212)
alpha-amino acid (CHEBI:33704)
amino acid (CHEBI:33709)
cofactor (CHEBI:23357)
flavonoid (CHEBI:47916)
riboflavin(1-) (CHEBI:57986)
neomycin (CHEBI:7507)
antimicrobial agent (CHEBI:33281)
isoflurane (CHEBI:6015)
morphine(1+) (CHEBI:58097)
microbiome (EFO:0004982)
pathogen (EFO:0000643)
strain (EFO:0005135)
total RNA (EFO:0004964)
software (EFO:0002029)
treatment (EFO:0000727)
time (EFO:0000721)
C57BL (EFO:0005181)
obsolete_intestine (EFO:0000834)
milligram per kilogram (EFO:0002902)
acid (EFO:0004416)
host (EFO:0000532)
rectal adenocarcinoma (EFO:0005631)
control (EFO:0001461)
placebo (EFO:0001674)
obsolete_antibiotic (EFO:0001485)
transcriptome (EFO:0004421)
genome (EFO:0004420)
light transmission aggregometry (MMO:0000249)
digestive tract (UBERON:0001555)
lower digestive tract (UBERON:0004907)
rostral octaval nerve motor nucleus (UBERON:2002175)
intestine (UBERON:0000160)
bile (UBERON:0001970)
tissue (UBERON:0000479)
male organism (UBERON:0003101)
regurgitated pellet (UBERON:0036018)
small intestine (UBERON:0002108)
digestive system (UBERON:0001007)
abomasum (UBERON:0007358)
tissue (MA:0003002)

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