Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System

Abstract

Goose can develop severe hepatic steatosis without overt injury, thus it may serve as a unique model for uncovering how steatosis-related injury is prevented. To identify the markedly prosteatotic and protective mechanisms, we performed an integrated analysis of liver transcriptomes and gut microbial metagenomes using samples collected from overfed and normally-fed geese at different time points. The results indicated that the fatty liver transcriptome, initially featuring a ‘metabolism’ pathway, was later joined by ‘cell growth and death’ and ‘immune diseases’ pathways. Gut microbiota played a synergistic role in the liver response as microbial and hepatic genes affected by overfeeding shared multiple pathways. Remarkably, the complement system, an inflammatory component, was comprehensively suppressed in fatty liver, which was partially due to increased blood lactic acid from enriched Lactobacillus. Data from in vitro studies suggested that lactic acid suppressed TNFα via the HNF1α/C5 pathway. In conclusion, gut microbes and their hosts respond to excess energy influx as an organic whole, severe steatosis and related tolerance of goose liver may be partially attributable to gut microbiotic products and suppressed complement system, and lactic acid from gut microbiota participates in the suppression of hepatic TNFα/inflammation through the HNF1α/C5 pathway.

Diet Consisting of Balanced Yogurt, Fruit, and Vegetables Modifies the Gut Microbiota and Protects Mice against Nonalcoholic Fatty Liver Disease

“…At the genera level, HFD consumption was associated with a higher abundance of Mucispirillum . This result was consistent with previous report . Furthermore, we observed that the ICR interventions significantly increased the species of Fecalibaculum .…”

Effects of floor- and net-reared systems on the intestinal growth and microbial diversity in the cecum of ducks

“…Considering that long-term stress could reduce the diversity of intestinal microbiota [30], this result may be because the ducks were raised on a net and unable to contact the natural environment. Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria were dominant in the cecum in both systems, and this result coincides with wild turkeys, captive broilers, caged Beijing ducks and oor-raised Landes geese [31][32][33][34].…”

Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis

“…Long-term heavy drinking is the main independent risk factor of fatty liver disease[ 25 ], but its pathogenesis is not clearly defined. Liu et al[ 26 ] found that gut microbiota played a synergistic role in the liver response, and the complement system was suppressed in fatty liver which was partially due to increased blood lactic acid from enriched Lactobacillus. Abnormal complement activation reportedly enhances the sensitivity of steatotic livers to ischemia and reperfusion injury, which leads to the development of fatty liver[ 27 , 28 ].…”