Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Singh S, Abu Y, Antoine D, Gomez D, Tao J, Truitt B, Roy S
Journal
Gut microbes
Year
2025
Keywords:
Prenatal opioid exposure, dysbiosis, gut microbiome, nociception, sex-based differences
The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including Lactobacillus compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.
Experiment 1
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Female offspring prenatally exposed to saline group (CSAL_F)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Female offspring prenatally exposed to opioids group (MSAL_F)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Offspring born to dams that were exposed to opioids (hydromorphone pre-gestationally followed by methadone during gestation), representing the prenatal opioid exposure condition
- Group 0 sample size Number of subjects in the control (unexposed) group
- 10
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- -V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Matched on Factors on which subjects have been matched on in a case-control study
- age
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Source: Figure 2C
Description: Microbiome analysis of female offspring (CSAL_F vs. MSAL_F) (n = 10 per group in all experiments).
Abundance in Group 1: increased abundance in Female offspring prenatally exposed to opioids group (MSAL_F)
Revision editor(s): Miss Lulu
Signature 2
Source: Figure 2C
Description: Microbiome analysis of female offspring (CSAL_F vs. MSAL_F) (n = 10 per group in all experiments).
Abundance in Group 1: decreased abundance in Female offspring prenatally exposed to opioids group (MSAL_F)
| NCBI | Quality Control | Links |
|---|---|---|
| UGC_005UGC_005 | ||
| Ruminococcus | ||
| Romboutsia | ||
| Monoglobus | ||
| Eubacterium xylanophilum | ||
| Lachnospiraceae bacterium NK4A136 | ||
| Lactobacillus |
Revision editor(s): Miss Lulu
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Male offspring prenatally exposed to saline group (CSAL_M)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Male offspring prenatally exposed to opioids group (MSAL_M)
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Source: Figure 3C
Description: Microbiome analysis of male offspring (CSAL_M vs. MSAL_M) (n = 10 per group in all experiments).
Abundance in Group 1: increased abundance in Male offspring prenatally exposed to opioids group (MSAL_M)
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Eubacterium ventriosum | ||
| Staphylococcus |
Revision editor(s): Miss Lulu
Signature 2
Source: Figure 3C
Description: Microbiome analysis of male offspring (CSAL_M vs. MSAL_M) (n = 10 per group in all experiments).
Abundance in Group 1: decreased abundance in Male offspring prenatally exposed to opioids group (MSAL_M)
Revision editor(s): Miss Lulu
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control female offspring without prenatal exposure to probiotics(CSAL_F)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Control female offspring with prenatal exposure to probiotics(CPRO_F)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Female offspring from control group exposed prenatally to probiotics
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Source: Figure 6C
Description: Microbiome analysis of control female offspring with or without prenatal exposure to probiotics (CPRO_F vs CSAL_F) (n = 10 per group in all experiments).
Abundance in Group 1: increased abundance in Control female offspring with prenatal exposure to probiotics(CPRO_F)
| NCBI | Quality Control | Links |
|---|---|---|
| Anaeroplasma | ||
| Eubacterium xylanophilum | ||
| Lachnoclostridium | ||
| Lactobacillus | ||
| Ligilactobacillus | ||
| Parvibacter | ||
| Romboutsia | ||
| ASF356ASF356 |
Revision editor(s): Miss Lulu
Signature 2
Source: Figure 6C
Description: Microbiome analysis of control female offspring with or without prenatal exposure to probiotics (CPRO_F vs CSAL_F) (n = 10 per group in all experiments).
Abundance in Group 1: decreased abundance in Control female offspring with prenatal exposure to probiotics(CPRO_F)
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacterium ventriosum | ||
| Odoribacter | ||
| Rickenellaceae_RC9Rickenellaceae_RC9 | ||
| Akkermansia | ||
| Bacteroides | ||
| Turicibacter | ||
| Faecalibaculum |
Revision editor(s): Miss Lulu
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