Administration of Alistipes indistinctus prevented the progression from nonalcoholic fatty liver disease to nonalcoholic steatohepatitis by enhancing the gut barrier and increasing Lactobacillus spp.

Metabolic-associated fatty liver disease (MAFLD) is an important public health problem, and the gut microbiota has become a new treatment target for MAFLD. Previously, A. indistinctus, a core gut bacterium, was shown to potentially contribute to the prevention of MAFLD. However, the effect and mechanism of A. indistinctus on MAFLD are still unclear and need to be investigated. This study primarily evaluated whether A. indistinctus can improve gut microbiota disorders and prevent the progression from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) in mice fed a high-fat diet (HFD). First, we observed that A. indistinctus significantly improved lipid metabolism disorders and reduced hepatic inflammation induced by HFD consumption in mice. We found that A. indistinctus improved gut barrier function and inhibited the LPS/TLR4/NF-κB pathway, thereby reducing hepatic inflammation. Moreover, 16S rRNA V3–V4 analyses revealed that A. indistinctus could significantly change the structure of the gut microbiota and increase the abundance of L. johnsonii by promoting its growth. Finally, we showed that L. johnsonii administration significantly improved lipid metabolism disorders and reduced hepatic lipid accumulation induced by HFD consumption in mice. In summary, A. indistinctus administration significantly reduces hepatic inflammation by improving gut barrier function and improves lipid metabolism disorders by promoting the growth of L. johnsonii. Our research improves the understanding of the gut microbiota and provides a basis for future therapeutic use of A. indistinctus.