Fig. 1

Timeline of the milestone events for the gut liver brain axis. In AD 300–400, Ge Hong collected folk remedies and published “Emergency Prescriptions for Elbow Reserve”, which firstly used fecal liquid to treat food poisoning and severe diarrhea. In 1899, Henry Tissier in France isolated the first strain of Bacillus bifidus from the feces of healthy breastfed infants. In 1900, German bacteriologist Paul Ehrlich discovered the blood–brain barrier. Metchnikoff proposed the famous “May hypothesis” in 1907, pointing out that the gut microbiota and its interactions with the host were crucial for health. In 1921, the concept of enteric nervous system (ENS) was first proposed, which focused on the neuroanatomy, function, and pathophysiology of gut-brain interactions. After six years, Wieland won the Nobel Prize in Chemistry for his discovery of bile acids and their chemical structures. In 1929, the George Burr couple discovered fatty acids were crucial for health. In 1950, gamma-aminobutyric acid (GABA) was discovered in the mammalian brain. In 1995, the concept of prebiotics was proposed by the international “father of prebiotics”, Glenn R. Gibson, and farnesoid X receptor (FXR) was first discovered by Forman et al. In 1998, Marshall proposed the concept of the “gut-liver axis”. Meanwhile, Rorberfroid further blended probiotics and prebiotics into products called synbiotics. In 2003, takeda G protein-coupled receptor 5 (TGR5) was first discovered as a cell surface receptor for bile acid reactions. In 2008, Wang first revealed the influence of the gut-brain-liver axis in human health. In 2012, the first gut-brain axis-related drug linaclotide was approved for the treatment of irritable bowel syndrome (IBS) by FDA. In 2016, the first gut-liver axis-related drug obeticholic acid was approved for the treatment of primary biliary cirrhosis by FDA. In 2022, the gut-brain axis-related drug vibrating capsule was approved for the treatment of functional constipation by FDA. Created with BioRender.com