Lactobacillus rhamnosus GG attenuates depression-like behaviour and cognitive deficits in chronic ethanol exposure mice by down-regulating systemic inflammatory factors

Addict Biol. 2024 Nov;29(11):e13445. doi: 10.1111/adb.13445.

Abstract

Ethanol can directly or indirectly lead to cognitive and mental disorders. The long-term intake of alcohol can directly affect the distribution of gut microbiota. Lactobacillus rhamnosus GG (LGG) is a natural bacterium isolated from healthy human intestines that has the function of preventing cytokine-induced cell apoptosis and protecting cell barriers. However, the regulatory effect of LGG on cognitive and mental disorders caused by chronic ethanol exposure (CEE) is still unclear. In this study, we established a CEE mouse model through free alcohol consumption and added LGG or antibiotics in the later stages of the model. Sequencing analysis of the 16S rRNA gene showed that CEE resulted in a decrease in the abundance and diversity of mouse gut microbial communities accompanied by alterations in the relative abundance of multiple enterobacterial genera. The use of LGG and antibiotics alleviated the depression-like behaviour and cognitive impairment of CEE-induced mice, reduced expression of inflammatory factors such as interleukin (IL)-6, IL-1β and tumour necrosis factor (TNF)-α in the ileum, serum and brain and increased the expression of synaptophysin (SYN), postsynaptic density protein-95 (PSD-95) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Together, LGG can alleviate depression-like behaviour caused by CEE in mice while also improving cognitive and memory functions through reducing peripheral and nervous system inflammation factors and balancing gut microbiota.

Keywords: Lactobacillus rhamnosus GG; chronic ethanol exposure; cognitive impairment; depression‐like behaviour.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Cognitive Dysfunction*
  • Cytokines / metabolism
  • Depression*
  • Disease Models, Animal*
  • Disks Large Homolog 4 Protein / metabolism
  • Down-Regulation / drug effects
  • Ethanol* / pharmacology
  • Gastrointestinal Microbiome* / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Ileum / metabolism
  • Inflammation
  • Interleukin-6 / metabolism
  • Lacticaseibacillus rhamnosus*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / pharmacology
  • Synaptophysin* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Ethanol
  • Brain-Derived Neurotrophic Factor
  • Synaptophysin
  • Bdnf protein, mouse
  • Dlg4 protein, mouse
  • Disks Large Homolog 4 Protein
  • Syp protein, mouse
  • Tumor Necrosis Factor-alpha
  • Cytokines
  • Anti-Bacterial Agents
  • Interleukin-6