Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

Gupta, Haripriya; Suk, Ki Tae; Kim, Dong Joon

doi:10.3390/jcm10030541

Cited by 28 publications

(41 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ethanol also activates an immune response in the brain conducted by an increased TLR4 pathway activation. It consequently induces inflammatory cytokines, such as TNF-α and IL-6, mediating neuroinflammation and blood-brain barrier impairment (Gupta et al, 2021). Inflammatory brain damage contributes to alcohol dependence after its chronic and heavy consumption.…”

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

“…Ammonia and other substances produced by the intestinal microbiota that are cleared by the liver can also be accumulated in ALD. Consequently, high circulating ammonia levels reaching the CNS induce astrocyte senescence, giving rise to a cascade of events leading to brain damage (Gupta et al, 2021). Brain imaging studies have demonstrated that hyperammonemia is related to astrocyte dysfunction (Ahluwalia et al, 2016).…”

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

“…Brain imaging studies have demonstrated that hyperammonemia is related to astrocyte dysfunction (Ahluwalia et al, 2016). Furthermore, an increased level of proinflammatory plasma cytokines, such as TNF-α, also contributes to this inflammatory brain damage (Gupta et al, 2021). Therefore, microbial products, ammonia, and inflammatory mediators produced by disturbances of the microbiota-gut-liver axis can worsen the neuroinflammation of the brain in ALD.…”

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

“…Although the mechanisms underlying this relationship are not fully described, it has been shown that alcohol and derived metabolites can modify some brain neurotransmitter signals, including γ-aminobutyric acid (GABA), glutamate, and dopamine circuits, with this effect influenced by the inflammation induced by changes of intestinal microbiota. Studies based on the use of magnetic resonance spectroscopy have demonstrated a high glutamine/ glutamate to creatinine ratio in alcoholic patients with hepatic encephalopathy (Gupta et al, 2021). Interestingly, it has been observed that Lactobacillus and Bifidobacterium can metabolize glutamate, an excitatory neurotransmitter that regulates glutamine/glutamate signaling, to produce GABA in the gut.…”

Section: Probiotics Benefit Addiction and Neuroinflammationmentioning

confidence: 99%

See 3 more Smart Citations

Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

et al. 2021

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) is one of the leading causes of morbidity among adults with alcohol use disorder (AUD) worldwide. Its clinical course ranges from steatosis to alcoholic hepatitis, progressing to more severe forms of liver damage, such as cirrhosis and hepatocellular carcinoma. The pathogenesis of ALD is complex and diverse elements are involved in its development, including environmental factors, genetic predisposition, the immune response, and the gut-liver axis interaction. Chronic alcohol consumption induces changes in gut microbiota that are associated with a loss of intestinal barrier function and inflammatory responses which reinforce a liver damage progression triggered by alcohol. Alcohol metabolites such as acetaldehyde, lipid peroxidation-derived aldehyde malondialdehyde (MDA), and protein-adducts act as liver-damaging hepatotoxins and potentiate systemic inflammation. Additionally, ethanol causes direct damage to the central nervous system (CNS) by crossing the blood-brain barrier (BBB), provoking oxidative stress contributing to neuroinflammation. Overall, these processes have been associated with susceptibility to depression, anxiety, and alcohol craving in ALD. Recent evidence has shown that probiotics can reverse alcohol-induced changes of the microbiota and prevent ALD progression by restoring gut microbial composition. However, the impact of probiotics on alcohol consumption behavior has been less explored. Probiotics have been used to treat various conditions by restoring microbiota and decreasing systemic and CNS inflammation. The results of some studies suggest that probiotics might improve mental function in Alzheimer’s, autism spectrum disorder, and attenuated morphine analgesic tolerance. In this sense, it has been observed that gut microbiota composition alterations, as well as its modulation using probiotics, elicit changes in neurotransmitter signals in the brain, especially in the dopamine reward circuit. Consequently, it is not difficult to imagine that a probiotics-based complementary treatment to ALD might reduce disease progression mediated by lower alcohol consumption. This review aims to present an update of the pathophysiologic mechanism underlying the microbiota-gut-liver-brain axis in ALD, as well as to provide evidence supporting probiotic use as a complementary therapy to address alcohol consumption disorder and its consequences on liver damage.

show abstract

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

Section: Alcohol and Microbiota-gut-liver-brain Axismentioning

confidence: 99%

Section: Probiotics Benefit Addiction and Neuroinflammationmentioning

confidence: 99%

See 2 more Smart Citations

Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, alcohol-induced changes in the gut microbiota may contribute not only to development of alcoholic liver disease, but also to a variety of CNS disorders (Engen et al 2015 ; García-Cabrerizo et al 2021 ). Indeed, it has been suggested that use of probiotic might be of potential use in prevention and treatment of alcohol-associated pathologies (Engen et al 2015 ; Lowe et al 2018 ; Rodriguez-Gonzalez and Orio 2020 ; Carbia et al 2021 ; Gupta et al 2021 ). In this regard, it was recently reported that butyrate (BUT) ameliorates alcoholic fatty liver disease in mice (Zhang et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line

et al. 2021

View full text Add to dashboard Cite

Alcohol use disorder (AUD), brought about by excessive alcohol use, is associated with damages to several organs including the brain. Chronic excessive use of alcohol can compromise intestinal integrity, leading to changes in gut microbiota (GM) composition known as dysbiosis. Dysbiosis, by disruption of the gut-brain axis (GBA), further exacerbates the deleterious effects of alcohol. One of the fermentation by-products of GM is butyrate (BUT), a short-chain fatty acid (SCFA) that plays an important role in maintaining homeostasis of the GBA. Alcohol metabolism results in formation of acetaldehyde, a highly reactive compound that reacts with dopamine in the brain to form toxic adducts such as salsolinol. Recent studies indicate potential neuro-protective effects of BUT against various toxicants including salsolinol. Here, we sought to investigate whether BUT can also protect against alcohol toxicity. Pretreatment of neuroblastoma-derived SH-SY5Y cells with 500 mM ethanol (ETOH) for 24 h resulted in approximately 40% reduction in cell viability, which was totally blocked by 10 µM of either BUT or AR 420,626 (AR), a selective fatty acid 3 receptor (FA3R) agonist. The neuro-protective effects of both BUT and AR were significantly (80%) attenuated by beta-hydroxy butyrate (BHB), a selective FA3R antagonist. Interestingly, combination of BUT and AR resulted in synergistic protection against ETOH, which was totally blocked by BHB. These findings suggest potential utility of butyrate and/or FA3R agonists against ETOH-induced toxicity.

show abstract

Lipopolysaccharide, arbiter of the gut–liver axis, modulates hepatic cell pathophysiology in alcoholism

Mak,

Shekhar

2024

The Anatomical Record

View full text Add to dashboard Cite

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)—a component of the outer membrane of gram‐negative bacteria—is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut‐liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut‐liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut‐liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

show abstract

Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

Cited by 28 publications

References 160 publications

Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

Probiotics-Based Treatment as an Integral Approach for Alcohol Use Disorder in Alcoholic Liver Disease

Sodium Butyrate Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line

Lipopolysaccharide, arbiter of the gut–liver axis, modulates hepatic cell pathophysiology in alcoholism

Contact Info

Product

Resources

About