The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence

Yang, Jun; Xiong, Pu; Bai, Ling; Zhang, Zunyue; Zhou, Yong; Chen, Cheng; Xie, Zhenrong; Xu, Yu; Chen, Ming‐Hui; Wang, Huawei; Zhu, Mei; Yu, Juehua; Wang, Kunhua

doi:10.3389/fnut.2021.765414

Cited by 14 publications

(8 citation statements)

References 61 publications

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“…In addition, compared with healthy subjects, intestinal microbiota changes in substance use disorders [ 6 ]. Harmful bacteria increase the production of inflammatory cytokines, triggering infiltration of inflammatory cells (such as neutrophils), leading to tissue damage and necrosis [ 7 , 8 ]. For example, gram-negative bacterial endotoxin (BT) is a potent activator of the host immune response and can activate the transcription factor nuclear factor kappa B [ 9 , 10 ], which leads to the production of cytokines [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts

Zhang

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To explore the potential link between gut damage and proinflammatory cytokines in heroin-dependent patients. Methods. We retrospectively analyzed and compared partial blood counts and biomarkers of intestinal injury and their potential correlations in 38 male heroin abuse patients and 29 healthy male participants. In addition, we compared and assessed proinflammatory cytokines and immune cells in 10 heroin abuse patients and 10 healthy participants. Results. Neutrophil counts, platelets/lymphocytes (PLR), neutrophils/lymphocytes (NLR), gut injury biomarkers, and proinflammatory cytokines, CD19+B in patients compared with healthy subjects’ cells increased significantly. The number of lymphocytes, CD3 CD4 T cells, and CD3 CD8 T cells decreased in patients compared to healthy individuals. When distinguishing between heroin addicts and healthy people, ROC/AUC analysis showed that a cutoff of 142.42 for PLR and 2.18 for NLR yielded a sensitivity of 65% and 85% and a specificity of 96.5% and 89.7%, respectively ( p = 0.001 , p < 0.001 ). For predicting intestinal injury, ROC/AUC analysis showed that a cutoff of 135.7 for PLR and 0.15 for NLR yielded a sensitivity of 52% and 60% and a specificity of 82% and 86.4%, respectively ( p = 0.003 , p = 0.009 ). Male heroin addicts are subject to intestinal injury and present with increased proinflammatory cytokine levels. Conclusion. NLR and PLR are possible indirect biomarkers for heroin dependence based on intestinal injury.

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Section: Introductionmentioning

confidence: 99%

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts

Zhang

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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“…The results from this analysis were in consensus with the literature on changes in opioid-induced metabolomics measured from metabolites in serum and urine [see review by Dinis-Oliveira ( 81 , 82 )]. Pathways predicted to be reduced by the PICRUSt2 analysis have been documented in studies on opioid-induced metabolomics to include vitamin biosynthesis ( 83 , 84 ), carbohydrate biosynthesis ( 85 , 86 ), propionic acid production ( 87 ), nucleotide biosynthesis ( 81 , 88 ), guanine degradation ( 89 ) and fatty acid and lipid biosynthesis ( 84 , 85 ). Those pathways predicted to increase also aligned with existing literature on opioid induced metabolomics alterations.…”

Section: Discussionmentioning

confidence: 99%

Long access heroin self-administration significantly alters gut microbiome composition and structure

Greenberg,

Winters,

Zagorac

et al. 2024

Front. Psychiatry

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IntroductionIt is well known that chronic opioid use disorder is associated with alterations in gastrointestinal (GI) function that include constipation, reduced motility, and increased bacterial translocation due to compromised gut barrier function. These signs of disrupted GI function can be associated with alterations in the gut microbiome. However, it is not known if long-access opioid self-administration has effects on the gut microbiome.MethodsWe used 16S rRNA gene sequencing to investigate the gut microbiome in three independent cohorts (N=40 for each) of NIH heterogeneous stock rats before onset of long-access heroin self-administration (i.e., naïve status), at the end of a 15-day period of self-administration, and after post-extinction reinstatement. Measures of microbial α- and β-diversity were evaluated for all phases. High-dimensional class comparisons were carried out with MaAsLin2. PICRUSt2 was used for predicting functional pathways impacted by heroin based on marker gene sequences.ResultsCommunity α-diversity was not altered by heroin at any of the three phases by comparison to saline-yoked controls. Analyses of β-diversity showed that the heroin and saline-yoked groups clustered significantly apart from each other using the Bray-Curtis (community structure) index. Heroin caused significant alterations at the ASV level at the self-administration and extinction phases. At the phylum level, the relative abundance of Firmicutes was increased at the self-administration phase. Deferribacteres was decreased in heroin whereas Patescibacteria was increased in heroin at the extinction phase. Potential biomarkers for heroin emerged from the MaAsLin2 analysis. Bacterial metabolomic pathways relating to degradation of carboxylic acids, nucleotides, nucleosides, carbohydrates, and glycogen were increased by heroin while pathways relating to biosynthesis of vitamins, propionic acid, fatty acids, and lipids were decreased.DiscussionThese findings support the view that long access heroin self-administration significantly alters the structure of the gut microbiome by comparison to saline-yoked controls. Inferred metabolic pathway alterations suggest the development of a microbial imbalance favoring gut inflammation and energy expenditure. Potential microbial biomarkers and related functional pathways likely invoked by heroin self-administration could be targets for therapeutic intervention.

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“…Metabolites produced by a healthy gut microbiota, such as short-chain fatty acids (e.g., acetic, propionic, and butyric acids), play important roles in maintaining the intestinal barrier, ( 43 ) providing energy ( 44 ) and immune homeostasis ( 45 ). It is well-recognized that gut microbiota also participate in modulating the intestinal microenvironment and host metabolism, while the gut microecology is vulnerable to the effects of unhealthy diet ( 46 ) and antibiotic treatments ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

Chen

Ikram

et al. 2022

Front. Nutr.

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The human gut microbiota has been proposed to serve as a multifunctional organ in host metabolism, contributing effects to nutrient acquisition, immune response, and digestive health. Fasting during Ramadan may alter the composition of gut microbiota through changes in dietary behavior, which ultimately affects the contents of various metabolites in the gut. Here, we used liquid chromatography–mass spectrometry-based metabolomics to investigate the composition of fecal metabolites in Chinese and Pakistani individuals before and after Ramadan fasting. Principal component analysis showed distinct separation of metabolite profiles among ethnic groups as well as between pre- and post-fasting samples. After Ramadan fasting, the Chinese and Pakistani groups showed significant differences in their respective contents of various fecal metabolites. In particular, L-histidine, lycofawcine, and cordycepin concentrations were higher after Ramadan fasting in the Chinese group, while brucine was enriched in the Pakistani group. The KEGG analysis suggested that metabolites related to purine metabolism, 2-oxocarboxylic acid metabolism, and lysine degradation were significantly enriched in the total subject population pre-fasting vs. post-fasting comparisons. Several bacterial taxa were significantly correlated with specific metabolites unique to each ethnic group, suggesting that changes in fecal metabolite profiles related to Ramadan fasting may be influenced by associated shifts in gut microbiota. The fasting-related differences in fecal metabolite profile, together with these group-specific correlations between taxa and metabolites, support our previous findings that ethnic differences in dietary composition also drive variation in gut microbial composition and diversity. This landscape view of interconnected dietary behaviors, microbiota, and metabolites contributes to the future development of personalized, diet-based therapeutic strategies for gut-related disorders.

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The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence

Cited by 14 publications

References 61 publications

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts

Platelet-To-Lymphocyte and Neutrophil-To-Lymphocyte Ratios Predict Intestinal Injury in Male Heroin Addicts

Long access heroin self-administration significantly alters gut microbiome composition and structure

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

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