Liver Injury, Endotoxemia, and Their Relationship to Intestinal Microbiota Composition in Alcohol-Preferring Rats

Autor: Loris Riccardo Lopetuso, Giancarlo Colombo, Valentina Petito, Gabriele Angelo Vassallo, Luca Masucci, Antonio Gasbarrini, Cristina Graziani, Carolina Mosoni, Maurizio Sanguinetti, Irene Lorrai, Paola Maccioni, Tiziana Cubeddu, Vincenzo Arena, Brunella Posteraro, Giovanni Addolorato, Francesco Paroni Sterbini, Cecilia Martini, Stefano Rocca
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Lipopolysaccharides
Male
medicine.medical_specialty
Necrosis
Lipopolysaccharide
Alcohol Drinking
Colon
Settore MED/12 - GASTROENTEROLOGIA
Medicine (miscellaneous)
Inflammation
Toxicology
Systemic inflammation
03 medical and health sciences
chemistry.chemical_compound
Liver Function Tests
Internal medicine
RNA
Ribosomal
16S

medicine
Animals
Liver Diseases
Alcoholic

Transaminases
Liver injury
business.industry
medicine.disease
Endotoxemia
Gastrointestinal Microbiome
Rats
Intestines
Psychiatry and Mental health
030104 developmental biology
Endocrinology
chemistry
Liver
Alcohol Use Disorder
Biological Markers
Blood Endotoxin Level
Sardinian Alcohol-Preferring Rats
Stool Microbiota
Psychiatry and Mental Health
Steatosis
medicine.symptom
business
Dysbiosis
Homeostasis
Fatty Liver
Alcoholic
Popis: Background There is strong evidence that alcoholism leads to dysbiosis in both humans and animals. However, it is unclear how changes in the intestinal microbiota (IM) relate to ethanol (EtOH)-induced disruption of gut-liver homeostasis. We investigated this issue using selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive EtOH consumption. Methods Independent groups of male adult sP rats were exposed to the standard, home-cage 2-bottle "EtOH (10% v/v) versus water" choice regimen with unlimited access for 24 h/d (Group Et) for 3 (T1), 6 (T2), and 12 (T3) consecutive months. Control groups (Group Ct) were composed of matched-age EtOH-naive sP rats. We obtained samples from each rat at the end of each experimental time, and we used blood and colon tissues for intestinal barrier integrity and/or liver pathology assessments and used stool samples for IM analysis with 16S ribosomal RNA gene sequencing. Results Rats in Group Et developed hepatic steatosis and elevated serum transaminases and endotoxin/lipopolysaccharide (LPS) levels but no other liver pathological changes (i.e., necrosis/inflammation) or systemic inflammation. While we did not find any apparent alteration of the intestinal colonic mucosa, we found that rats in Group Et exhibited significant changes in IM composition compared to the rats in Group Ct. These changes were sustained throughout T1, T2, and T3. In particular, Ruminococcus, Coprococcus, and Streptococcus were the differentially abundant microbial genera at T3. The KEGG Ortholog profile revealed that IM functional modules, such as biosynthesis, transport, and export of LPS, were also enriched in Group Et rats at T3. Conclusions We showed that chronic, voluntary EtOH consumption induced liver injury and endotoxemia together with dysbiotic changes in sP rats. This work sets the stage for improving our knowledge of the prevention and treatment of EtOH-related diseases.
Databáze: OpenAIRE