Dataset Information

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

ABSTRACT: The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

SUBMITTER: Yang J

PROVIDER: S-EPMC8600332 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Yang Jiqing J Xiong Pu P Bai Ling L Zhang Zunyue Z Zhou Yong Y Chen Cheng C Xie Zhenrong Z Xu Yu Y Chen Minghui M Wang Huawei H Zhu Mei M Yu Juehua J Wang Kunhua K

Frontiers in nutrition 20211104

The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightl ...[more]

PMID: 34805249

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Project description:ObjectiveThe orphan nuclear receptor Nur77 is an important factor regulating metabolism. Nur77 knockout mice become obese with age, but the cause of obesity in these mice has not been fully ascertained. We attempted to explain the cause of obesity in Nur77 knockout mice from the perspective of the gut microbiota and to investigate the inhibitory effect of calcipotriol combined with BRD9 inhibitor (iBRD9) on obesity.MethodsEight-week-old wild-type mice and Nur77 knockout C57BL/6J mice were treated with calcipotriol combined with iBRD9 for 12 weeks. Mouse feces were collected and the gut microbiota was assessed by analyzing 16S rRNA gene sequences. The bacterial abundance difference was analyzed, and the intestinal mucosal tight junction protein, antimicrobial peptide, and inflammatory cytokine mRNA levels of the colon and serum LPS and inflammatory cytokine levels were measured.ResultsCalcipotriol combined with iBRD9 treatment reduced the body weight and body fat percentage in Nur77 knockout mice. In the gut microbiota of Nur77 knockout mice, the relative abundances of Lachnospiraceae and Prevotellaceae decreased, and Rikenellaceae increased; while Rikenellaceae decreased after treatment (p < 0.05). Correspondingly, the mRNA levels of intestinal mucosal tight junction proteins (occludin (Ocln), claudin3 (Cldn3)) in the colons of Nur77 knockout mice were significantly decreased, and they increased significantly after treatment (p < 0.001). The mRNA levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) were significantly increased in Nur77 knockout mice, and TNF-α and IL-6 levels were significantly decreased after treatment (p < 0.05, <0.01, or <0.001). The levels of serum LPS, TNF-α, and IL-1β in Nur77 knockout mice were significantly increased (p < 0.05). Serum LPS, TNF-α, and IL-6 levels were significantly decreased after treatment (p < 0.05 or <0.01).ConclusionsCalcipotriol combined with iBRD9 can regulate the gut microbiota, improve intestinal mucosal barrier function, reduce LPS absorption into the blood, and alleviate obesity in Nur77 knockout mice.

Project description:IntroductionThe global health challenge of ulcerative colitis (UC) has been classified by the WHO as a modern refractory disease, commonly referred to as green cancer, with limited treatment options still available, highlighting the urgent need for the development of new therapeutic strategies. Recent pharmacological research has shown that traditional Chinese medicine saussurea costus (SC) possesses beneficial antibacterial and anti-inflammatory properties. Nevertheless, its underlying mechanism remains elusive.MethodsFirstly, we identified the main active components of SC through UHPLC-QTOF-MS analysis. Subsequently, UC mice were induced using DSS and administered different doses of SC to evaluate its efficacy. Additionally, the impact of SC on the repair of the intestinal mucosal barrier was evaluated through immunofluorescence and western blot. Furthermore, 16s rRNA gene sequencing was conducted to elucidate the contribution of gut microbiota to UC pathogenesis.ResultsThe primary components of SC include Proline, Phenylalanine, Isoleucine, Lucidenic acid M, and Pyroglutamic acid. The efficacy of SC was concurrently assessed, revealing its potential to ameliorate histological injury in colitis mice. Furthermore, SC was found to decrease levels of TNF-α, IL-1β, IL-8, and IL-18 while promoting the expression of IL-10 and IL-22. Similarly, we also found that the expression of ZO-1 and Occludin was reversed by SC in colitis mice. In addition, analysis of 16S rRNA gene sequencing indicated that SC reduced harmful bacterial populations, such as Proteobacteria, while simultaneously enhancing the levels of beneficial bacteria like Lactobacillus, thereby contributing to the improvement of UC pathology.ConclusionThis study highlights the therapeutic potential of SC in managing UC through its ability to attenuate inflammatory responses, restore intestinal barrier functionality, and modulate gut microbiota composition, which findings offer insights into potential strategies for advancing UC treatment.

Dataset Information

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

Publications

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

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