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2.
J Mycol Med ; 30(4): 101046, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33067115
3.
EBioMedicine ; 55: 102769, 2020 May.
Article in English | MEDLINE | ID: mdl-32403084

ABSTRACT

BACKGROUND: Multiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype. METHODS: Outbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype. RESULTS: Overall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae. CONCLUSIONS: These data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex.


Subject(s)
Cocaine-Related Disorders/microbiology , Cocaine/pharmacology , Conditioning, Operant/drug effects , Delay Discounting/drug effects , Locomotion/drug effects , Reinforcement, Psychology , Animals , Animals, Outbred Strains , Bacteroidetes/classification , Bacteroidetes/genetics , Bacteroidetes/isolation & purification , Cecum/microbiology , Clostridiales/classification , Clostridiales/genetics , Clostridiales/isolation & purification , Cocaine-Related Disorders/physiopathology , Cocaine-Related Disorders/psychology , Conditioning, Operant/physiology , Delay Discounting/physiology , Euryarchaeota/classification , Euryarchaeota/genetics , Euryarchaeota/isolation & purification , Female , Firmicutes/classification , Firmicutes/genetics , Firmicutes/isolation & purification , Gastrointestinal Microbiome/genetics , Impulsive Behavior/physiology , Locomotion/physiology , Male , Phenotype , Proteobacteria/classification , Proteobacteria/genetics , Proteobacteria/isolation & purification , RNA, Ribosomal, 16S/genetics , Rats , Sex Factors
6.
Neurotox Res ; 35(1): 111-121, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30066173

ABSTRACT

A role of the gut microbiota in influencing brain function and emotional disorders has been suggested. However, only a few studies have investigated the gut microbiota in the context of drug addiction.Cocaine can be smoked (i.e., crack or coca paste) and its consumption is associated with a very high abuse liability and toxicity. We have recently reported that cocaine base seized samples contained caffeine and phenacetin as main active adulterants, which may potentiate its motivational, reinforcing, and toxic effects. However, the effect of volatilized cocaine and adulterants on the gut microbiota remained unknown. In the present study, we evaluated the effect of volatilized cocaine and two adulterants on the structure, diversity, and functionality of the gut microbiota in rats. Animals were chronically exposed to the fume of cocaine, caffeine, and phenacetin during 14 days. At the end of the treatment, feces were collected and the structure, composition, and functional predictions of the gut microbiota were analyzed. Cocaine significantly decreased the community richness and diversity of the gut microbiota while both cocaine and phenacetin drastically changed its composition. Phenacetin significantly increased the Firmicutes-Bacteroidetes ratio compared to the control group. When the predicted metagenome functional content of the bacterial communities was analyzed, all the treatments induced a dramatic decrease of the aromatic amino acid decarboxylase gene. Our findings suggest that repeated exposure to volatilized cocaine, as well as to the adulterants caffeine and phenacetin, leads to changes in the gut microbiota. Future studies are needed to understand the mechanisms underlying these changes and how this information may support the development of novel treatments in drug addiction.


Subject(s)
Caffeine/administration & dosage , Central Nervous System Agents/administration & dosage , Cocaine/administration & dosage , Gastrointestinal Microbiome/drug effects , Phenacetin/administration & dosage , Animals , Biodiversity , Cocaine-Related Disorders/microbiology , Feces/microbiology , Gastrointestinal Microbiome/genetics , Illicit Drugs/pharmacology , Male , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis , Random Allocation , Rats, Wistar , Volatilization
7.
BMJ Case Rep ; 20172017 Aug 07.
Article in English | MEDLINE | ID: mdl-28784893

ABSTRACT

We present the case of a 28-year-old man with a long-standing history of cocaine abuse and Child-Pugh class C alcoholic liver cirrhosis who developed severe lower respiratory tract infection complicated with septic shock and multiple organ dysfunction. He was managed in the intensive care unit. On the eighth day after admission, he developed a nose discolouration, which was initially thought to be associated with high-dose vasopressors. Despite the reduction of vasopressors, the lesion progressed rapidly. It was later diagnosed as rhinocerebral mucormycosis. Amphotericin B was administered, but unfortunately the patient succumbed to the complications postinfection. The association between alcoholic liver cirrhosis and rhinocerebral mucormycosis should be known and prompt recognition warrants immediate treatment.


Subject(s)
Brain/microbiology , Central Nervous System Fungal Infections/microbiology , Cocaine-Related Disorders/microbiology , Liver Cirrhosis, Alcoholic/microbiology , Mucormycosis/microbiology , Rhinitis/microbiology , Adult , Fatal Outcome , Humans , Male
8.
Oral Dis ; 23(3): 324-330, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27982490

ABSTRACT

OBJECTIVE: To compare counts of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis and Fusobacterium nucleatum between crack users and non-users. MATERIALS AND METHODS: A cross-sectional study was conducted involving seventy-four crack cocaine users and eighty-one non-users matched for age, gender and tobacco use. Demographic and clinical variables were analysed. Subgingival bacterial samples were collected from four sites with the greatest probing depths and were analysed using real-time polymerase chain reaction. RESULTS: No significant difference was found in the prevalence of total counts for each bacterial species analysed between groups. However, crack users had a 1.85 (95% CI: 1.03-3.31), 2.19 (95% CI 1.24-3.88), 2.53 (95% CI 1.27-5.04) and 2.40 (95% CI 1.22-4.75) greater probability of having the higher counts (≥75th percentile) for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, respectively. CONCLUSION: Although some crack users had higher (>75th percentile) bacterial counts for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, total counts did not differ between crack users and non-users, leading to the hypothesis that the higher occurrence of periodontitis on crack users may be related to other non-bacterial factors.


Subject(s)
Cocaine-Related Disorders/epidemiology , Cocaine-Related Disorders/microbiology , Periodontitis/epidemiology , Periodontium/microbiology , Adult , Aggregatibacter actinomycetemcomitans , Case-Control Studies , Crack Cocaine , Cross-Sectional Studies , Female , Fusobacterium nucleatum , Humans , Male , Porphyromonas gingivalis , Prevalence , Prevotella intermedia , Young Adult
10.
J Stud Alcohol Drugs ; 75(2): 347-57, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24650829

ABSTRACT

OBJECTIVE: HIV and illicit drug use have been associated with altered nutrition, immune function, and metabolism. We hypothesized that altered composition and decreased diversity of the intestinal microbiota, along with microbial translocation, contribute to nutritional compromise in HIV-infected drug users. METHOD: We enrolled 26 men and 6 women, 15 HIV infected and 17 HIV uninfected, in this exploratory, cross-sectional study; 7 HIV-infected and 7 HIV-uninfected participants had used cocaine within the previous month. We examined the independent effects of cocaine use and HIV infection on the composition and diversity of the intestinal microbiota, determined by 16S rRNA gene pyrosequencing. Using dietary records, anthropometrics, and dual x-ray absorptiometry, we examined the additional effects of nutritional indices on the intestinal microbiota. We compared markers of inflammation and microbial translocation between groups. RESULTS: Cocaine users had a higher relative abundance of Bacteroidetes (M ± SD = 57.0% ± 21 vs. 37.1% ± 23, p = .02) than nonusers. HIV-infected individuals had a higher relative abundance of Proteobacteria (Mdn [interquartile range] = 1.56% [0.5, 2.2] vs. 0.36% [0.2, 0.7], p = .03), higher levels of soluble CD14 and tumor necrosis factor-α, and lower levels of anti-endotoxin core antibodies than uninfected subjects. HIV-infected cocaine users had higher interferon-γ levels than all other groups. Food insecurity was higher in HIV-infected cocaine users. CONCLUSIONS: We identified differences in the relative abundance of major phyla of the intestinal microbiota, as well as markers of inflammation and microbial translocation, based on cocaine use and HIV infection. Nutritional factors, including alcohol use and lean body mass, may contribute to these differences.


Subject(s)
Bacterial Translocation/physiology , Cocaine-Related Disorders/microbiology , HIV Infections/microbiology , Intestinal Mucosa/microbiology , Intestinal Mucosa/physiology , Microbiota/physiology , Adult , Cocaine-Related Disorders/epidemiology , Cohort Studies , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Inflammation/epidemiology , Inflammation/microbiology , Longitudinal Studies , Male , Middle Aged , Nutritional Status/physiology
12.
Neth J Med ; 64(7): 248-51, 2006.
Article in English | MEDLINE | ID: mdl-16929087

ABSTRACT

Three male patients aged 29, 30 and 34 years and a 36-year-old female are reported with nasal septum perforation and a history of cocaine abuse. Two of the patients also had a perforation of the hard palate. In all four, antineutrophil cytoplasmic antibodies (ANCA) were found. One had a cytoplasmic immunofluorescence-staining pattern (c-ANCA), the other three showed a perinuclear staining pattern (p-ANCA). Furthermore, all patients were found to be nasal carriers of S. aureus. We hypothesise that tissue damage to the nasal and palatal area in patients using cocaine may partly be mediated by the presence of ANCA antibodies. Furthermore, we speculate that S. aureus facilitates the development of these ANCA antibodies.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic/analysis , Cocaine-Related Disorders/complications , Maxillary Sinus/pathology , Nasal Septum/pathology , Nose Diseases/etiology , Staphylococcal Infections/pathology , Staphylococcus aureus , Adult , Cocaine-Related Disorders/microbiology , Female , Fluorescent Antibody Technique , Humans , Male , Maxillary Sinus/microbiology , Nasal Mucosa/pathology , Nasal Septum/microbiology , Nose Diseases/immunology , Nose Diseases/microbiology , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology
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