Noni (Morinda citrifolia L.) fruit phenolic extract supplementation ameliorates NAFLD by modulating insulin resistance, oxidative stress, inflammation, liver metabolism and gut microbiota.

The liver-protective activity of phenolics has been consistently reported, but the underlying protective mechanism of phenolic extract from noni fruit (NFE) against high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) remains unclear. Mice were fed with HFD or combination of HFD and NFE for 10 weeks, and then the gut microbiota and liver metabolites were compared. In this study, NFE supplementation alleviated HFD-induced liver injury and metabolic comorbidities, as evidenced by reduced liver function markers, decreased lipid profile levels, and improved obesity and insulin resistance. NFE supplementation restored the composition of gut microbiota with a remarkable elevation in the relative abundance of Parabacteroides, Lactobacillus, Roseburia, Akkermansia and a significant reduction in Helicobacter, norank_f_Desulfovibrionaceae, Desulfovibrio, Mucispirillum at the genus level. Liver metabolomics demonstrated that NFE supplementation favorably regulated the metabolic pathways involved in oxidative stress and inflammation, including purine metabolism, glutathione metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism, pentose phosphate pathway, ascorbate and aldarate metabolism, galactose metabolism etc. Furthermore, NFE supplementation inhibited the HFD-induced activation of the liver endotoxin - TLR4 - NF-κB pathway, and alleviated liver inflammation. In conclusion, the findings of this study provide new evidences supporting that NFE can be used as a therapeutic approach for HFD-induced NAFLD via modulating the gut microbiota composition, liver metabolite profile and suppressing inflammatory reaction.