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However, the underlying mechanisms are yet to be clarified. We hypothesised that BA signalling may be required for the glucose-lowering effects and metabolic benefits of AGI.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Leptin receptor (<jats:italic>Lepr<\/jats:italic>)-knockout (KO) <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice and high-fat high-sucrose (HFHS)-fed <jats:italic>Fxr<\/jats:italic> (also known as <jats:italic>Nr1h4<\/jats:italic>)-KO mice were treated with AGI. Metabolic phenotypes and BA signalling in different compartments, including the liver, gut and endocrine pancreas, were evaluated. BA pool profiles were analysed by mass spectrometry. The islet transcription profile was assayed by RNA sequencing. The gut microbiome were assayed by 16S ribosomal RNA gene sequencing.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>AGI lowered microbial BA levels in BA pools of different compartments in the body, and increased gut BA reabsorption in both <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> and HFHS-fed mouse models via altering the gut microbiome. The AGI-induced changes in BA signalling (including increased activation of farnesoid X receptor [FXR] in the liver and inhibition of FXR in the ileum) echoed the alterations in BA pool size and composition in different organs. In <jats:italic>Fxr<\/jats:italic>-KO mice, the glucose- and lipid-lowering effects of AGI were partially abrogated, possibly due to the <jats:italic>Fxr<\/jats:italic>-dependent effects of AGI on decelerating beta cell replication, alleviating insulin hypersecretion and improving hepatic lipid and glucose metabolism.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions\/interpretation<\/jats:title>\n<jats:p>By regulating microbial BA metabolism, AGI elicited diverse changes in BA pool composition in different host compartments to orchestrate BA signalling in the whole body. The AGI-induced changes in BA signalling may be partly required for its glucose-lowering effects. Our study, hence, sheds light on the promising potential of regulating microbial BA and host FXR signalling for the treatment of type 2 diabetes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Data availability<\/jats:title>\n<jats:p>Sequencing data are available from the BioProject Database (accession no. 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