Alistipes indistinctus could prevnet progression from NASL to NASH by improving gut barrier and enriching lactobacillus spp.

Metabolic Associated Fatty Liver Disease MAFLD has been an important public health problem and gut microbiota has become a new target of MAFLD. Previously, it has been proven that A indistinctus, a gut core bacteria, might contribute to prevent MAFLD. However, the effect and mechanism of A indistinctus on MAFLD still unclear and need to be investigated. This study primarily evaluated whether Alistipes indistinctus can regulate fat metabolism and improve gut microbiota disorder in mice fed with a highfat diet HFD. Firstly, we observed that A indistinctus significantly improved lipid metabolism disorders and reduced hepatic inflammation induced by a HFD in mice. Then we found that A indistinctus could improve the gut barrier function and inhibit the LPSTLR4NFB pathway thereby reduce hepatic inflammation. Meanwhile, 16S rRNA V3V4 analyses also revealed that A indistinctus could significantly change the structure of gut microbiota, and increase the abundance of L johnsonii by promoting its growth. Finally, we showed that L johnsonii could significantly improved lipid metabolism disorders and reduced hepatic inflammation induced by a HFD in mice. In summary, A indistinctus significantly reduces hepatic inflammation by improving gut barrier function and improved lipid metabolism disorders by promoting the growth of L johnsonii. Our research improved understanding of gut microbiota and provided the basis for further use of A indistinctus.