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Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model
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Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model
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Journal Article
Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model
2026
Overview
Background
Opioid dependence, particularly morphine, has been linked to gut microbiota dysbiosis and systemic inflammation, yet the interplay between gut microbial alterations and hepatic inflammatory responses remains poorly understood.
Methods
Fifty male Wistar rats were separated into two groups, one received escalating morphine doses (5 to 30 mg/kg over 10 days), while the other acted as a saline control. Fecal samples were collected at baseline, on days 5 and 10 of treatment, and after a 10-day withdrawal. DNA was extracted for qPCR analysis of
Lactobacillus
,
Bifidobacterium
,
Clostridium
,
Bacteroides
, and
Faecalibacterium
. Liver tissues were examined for inflammatory markers (
TNF-α
,
IFN-γ
,
IL-6
,
NF-κB
) using RT-qPCR after treatment and withdrawal.
Results
A significant decline in
Lactobacillus
(
P
= 0.011) and
Bifidobacterium
(
P
= 0.003) following morphine treatment, with partial recovery observed after withdrawal (
P
= 0.014;
P
= 0.0009), yet levels remained below baseline. Conversely,
Clostridium
levels increased significantly during treatment (
P
= 0.0001), persisting at elevated levels post-withdrawal (
P
= 0.0001).
Bacteroides
and
Faecalibacterium
also exhibited decreased abundances during morphine treatment (
P
> 0.05;
P
= 0.00009), with limited recovery thereafter (
P
> 0.05;
P
= 0.00008). Hepatic analysis revealed elevated levels of
TNF-α
(
P
< 0.0001),
IL-6
(
P =
0.005), and
NF-κB
(
P =
0.41), alongside a significant reduction in
IFN-γ
(
P
< 0.001) expression in the morphine group compared to controls. After withdrawal,
TNF-α
(
P
< 0.01) and
IFN-γ
(
P
= 0.004) levels decreased, while
NF-κB
(
P
= 0.03) and
IL-6
(
P =
0.4(remained elevated, indicating persistent inflammatory responses.
Conclusion
Morphine causes lasting gut dysbiosis and liver inflammation, indicating disruption of the gut-liver axis in opioid dependence. These results emphasize morphine’s impact on gut microbiota and liver health, suggesting significant long-term effects of opioid use. Targeting microbiota modulation and anti-inflammatory approaches may offer therapeutic options for opioid-related conditions.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Feces
/ Gastrointestinal Microbiome - drug effects
/ Interferon-gamma - metabolism
/ Liver
/ Male
/ Medicine
/ Morphine
/ Morphine - administration & dosage
/ Morphine Dependence - complications
/ Morphine Dependence - microbiology
/ Opioids
/ Rats
/ Substance Withdrawal Syndrome - microbiology
