Gut liver brain axis in diseases: the implications for therapeutic interventions

Abstract

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

Periodic heat waves-induced neuronal etiology in the elderly is mediated by gut-liver-brain axis: a transcriptome profiling approach

“…The liver-brain axis is a vital communication network influencing human health, connecting the gut, liver, and brain. It plays a role in various disease conditions involving endocrine, humoral, metabolic, and immune pathways 69 . The impact of climate change on neurological diseases and gastrointestinal health, including the liver-brain axis, has been highlighted, with potential implications for metabolic liver diseases and associated neuropathologies 70 .…”

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…This leaky gut condition, marked by heightened intestinal permeability and resulting in symptoms like chronic diarrhea, constipation, and bloating, contributes to systemic inflammation. Importantly, it may also impact cognitive functions [101]. MAFLD is also linked to various neurological manifestations, including reductions in brain volume, cognitive impairment, and cerebrovascular disease [102].…”

Mechanism Explanation on Improved Cognitive Ability of D-Gal Inducing Aged Mice Model by Lactiplantibacillus plantarum MWFLp-182 via the Microbiota–Gut–Brain Axis

“…The liver plays an important role in the microbiota-gut-brain axis, and the gut barrier is the bridge linking the gut microbiota to the liver. If the gut barrier is compromised, harmful metabolites can enter the liver, leading to oxidative damage and inflammatory responses, which in turn can affect the neural feedback between the liver and the brain . Elevated cholesterol levels in the liver of older individuals can lead to metabolic disturbances, which may potentially contribute to AD …”

“…If the gut barrier is compromised, harmful metabolites can enter the liver, leading to oxidative damage and inflammatory responses, which in turn can affect the neural feedback between the liver and the brain. 15 Elevated cholesterol levels in the liver of older individuals can lead to metabolic disturbances, which may potentially contribute to AD. 16 Probiotics are defined as "live microorganisms", capable of conferring health benefits to the host when administered in adequate amounts and can regulate gut microbiota directly.…”