SIRT3 Deficiency Promotes High‐Fat Diet‐Induced Nonalcoholic Fatty Liver Disease in Correlation with Impaired Intestinal Permeability through Gut Microbial Dysbiosis

Abstract

Scope Sirtuin 3 (SIRT3) plays a protective role against nonalcoholic fatty liver disease (NAFLD) by improving hepatic mitochondrial dysfunction. Gut microbiota imbalance contributes to the pathogenesis of NAFLD, yet the underlying mechanism linking SIRT3 with gut microbiota in NAFLD progression remains obscure. Methods and results Wild‐type 129 mice and SIRT3 knockout (SIRT3KO) mice are placed under a chow diet or high‐fat diet (HFD) treatment for 18 weeks. HFD resulted in a significantly increased hepatic steatosis and inflammation, which are exacerbated in SIRT3KO mice. The gut microbiota by 16s rRNA gene sequencing and phylogenetic reconstruction of unobserved states analysis are characterized. Lack of SIRT3 facilitates gut microbial dysbiosis in mice following HFD, with increased Desulfovibrio, Oscillibacter, and decreased Alloprevotella. SIRT3 deficiency resulted in an impaired intestinal permeability and inflammation in HFD‐fed mice, which can be attenuated by sodium butyrate (NaB). SIRT3KO HFD‐fed mice is followed by an increased lipopolysaccharide into the circulation and dysregulated expressions of cannabinoid receptor 1 and 2 in colon and liver, which are significantly associated with the alterations of intestinal microbiota. Conclusions SIRT3 deficiency promotes NAFLD progression in correlation with impaired intestinal permeability through gut microbiota dysbiosis.

Bifidobacterium longum R0175 Protects Rats against d -Galactosamine-Induced Acute Liver Failure

“…The elevated relative abundance of Oscillibacter spp. correlated with the severity of NAFLD (41). In our study, pretreatment with B. longum R0175 significantly reduced the enrichment of Butyricimonas spp., B. virosa, and Oscillibacter spp., indicating that the shifts in the relative abundances of these microbes may be implicated in the protective effects of the probiotic against acute liver failure in rats.…”

“…and intestinal mucosal injury scores, which was consistent with previous studies showing that the enrichment of Oscillibacter spp. positively correlated with intestinal mucosal barrier impairment (40,41). We found that the R0175 group harbored an increased relative abundance of bacteria of the genus Alloprevotella, which can indirectly produce short-chain fatty acids (SCFAs).…”

Camellia sinensis and Litsea coreana Ameliorate Intestinal Inflammation and Modulate Gut Microbiota in Dextran Sulfate Sodium‐Induced Colitis Mice

“…Notably, Chen et al. suggested the crucial role of Oscillibacter in high fat diet‐induced intestinal dysfunction, but also the positive association with digestive diseases and more severe DSS‐induced colitis . In our study, the relative abundance of Oscillibacter was increased by DSS administration and was attenuated by TEs treatment, which is consistent with Peng et al.…”

“…Significant attenuation of DSS‐induced increase in Oscillibacter were observed in all TE‐treated groups. The positive and negative effects of Oscillibacter were reported in various literature . Arpaia et al.…”

Capsaicin Improves Glucose Tolerance and Insulin Sensitivity Through Modulation of the Gut Microbiota‐Bile Acid‐FXR Axis in Type 2 Diabetic db/db Mice

“…The animal diet was provided as previously described . Briefly, chow diet (10% fat, 70% carbohydrate, 20% protein; D12450H) was obtained from Research Diets.…”