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.

Wang R ，Wang L ，Wu H ，Zhang L ，Hu X ，Li C ，Liu S ... -  《-》

Phenolics from noni (Morinda citrifolia L.) fruit alleviate obesity in high fat diet-fed mice via modulating the gut microbiota and mitigating intestinal damage.

Noni fruit has certain anti-obesity effect. However, the bioactive ingredients in noni fruit that contribute to anti-obesity activity as well as the relation between its anti-obesity activity and gut microbiota remain unclear. In this study, obese mice induced by high-fat diet (HFD) and were intervened with noni fruit phenolic extract (NFE) for 10 weeks. The results showed NFE supplementation decreased body weight, lipid accumulation in liver andadiposetissues, ameliorated gut microbiota dysbiosis by increasing short-chain fatty acid (SCFA)-producing bacteria and decreasing lipopolysaccharide (LPS)-producing bacteria, and mitigated intestinal inflammation and oxidative stress. Moreover, NFE supplementation improved intestinal barrier dysfunction by elevating the protein expression levels of Claudin-1, Occludin and ZO-1, alleviated the HFD-induced intestinal inflammation by repressing the LPS/TLR4/NF-κB pathway. Collectively, the findings revealed NFE intervention inhibits obesity by improving gut microbiota disorder, barrier function, and inflammation. Hence, NFE may be an effective way to ameliorate HFD-induced damage.

Wang R ，Wang L ，Wang S ，Wang J ，Su C ，Zhang L ，Li C ，Liu S ... -  《-》

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation.

Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism gene expression deregulation. Our results support the suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory, antioxidant and prebiotic integrative response.

Porras D ，Nistal E ，Martínez-Flórez S ，Pisonero-Vaquero S ，Olcoz JL ，Jover R ，González-Gallego J ，García-Mediavilla MV ，Sánchez-Campos S ... -  《-》

Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis.

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.

Wang P ，Wang J ，Li D ，Ke W ，Chen F ，Hu X ... -  《-》

Alleviating effects of noni fruit polysaccharide on hepatic oxidative stress and inflammation in rats under a high-fat diet and its possible mechanisms.

Yang X ，Mo W ，Zheng C ，Li W ，Tang J ，Wu X ... -  《-》