Effects of Resveratrol Administration in Liver Injury Prevention as Induced by an Obesogenic Diet: Role of Ruminococcaceae

Abstract

Gut microbiota dysbiosis has been described in several metabolic disruptions, such as non-alcoholic fatty liver disease (NAFLD). Administration of resveratrol has been claimed to elicit benefits against NAFLD along with modulating gut microbiota composition. This investigation aims to study the putative mediating role of gut microbiota in the potential hepato-protective effects of resveratrol in a diet-induced NAFLD rat model. The involvement of bacteria from the Ruminococcaceae family in such effects was also addressed. Resveratrol administration resulted in lowered liver weight and serum total and non-HDL cholesterol concentrations, as well as in increased serum HDL cholesterol levels. The administration of this polyphenol also prevented obesogenic diet-induced serum transaminase increases. In addition, histopathological analysis revealed that resveratrol administration ameliorated the dietary-induced liver steatosis and hepatic inflammation. Gut microbiota sequencing showed an inverse relationship between some bacteria from the Ruminococcaceae family and the screened hepatic markers, whereas in other cases the opposite relationship was also found. Interestingly, an interaction was found between UBA-1819 abundance and resveratrol induced liver weight decrease, suggesting that for this marker resveratrol induced effects were greater when the abundance of this bacteria was high, while no actions were found when UBA-1819 abundance was low.

Keywords: NAFLD; Ruminococcaceae; fructose; microbiota; resveratrol.

Figure 1

Final body weight and body weight increase (A), liver weight and food intake (B), serum total, HDL, and non-HDL cholesterol levels (C) and serum aminotransferase levels (D) in rats fed a control diet (C), a high-fat high-fructose diet (HFHF) or a high-fat-high-fructose diet supplemented with 30 mg/kg/d resveratrol (RSV30). Values are presented as mean ± SEM. Bars not sharing common letters are significantly different (p < 0.05). ALT: alanine aminotransferase, AST: aspartate aminotransferase.

Figure 2

Microbial diversity according to the Shannon index (A) and histogram representing the relative abundances of bacteria within the Ruminococcaceae family (B) measured in faecal samples in rats fed a control diet (C), a high-fat high-fructose diet (HFHF) or a high-fat-high-fructose diet supplemented with 30 mg/kg/d resveratrol (RSV30).

Figure 3

Representative heatmap of the Spearman correlation values of the most abundant Ruminococcaceae family microbes and studied liver damage markers. +/− = p < 0.05, + +/− − = p < 0.01.

Figure 4

Graphic representation of liver weight (A), serum ALT (B) and serum AST (C) levels according to the relative abundance of Ruminococcaceae UCG-014, Ruminococcaceae UCG-005, UBA-1819, Fourneriella and Eubacterium corpostalonigenes in rats fed a control diet (C), a high-fat high-fructose diet (HFHF) or a high-fat-high-fructose diet supplemented with 30 mg/kg/d resveratrol (RSV30). Values are presented as mean ± SEM. Bars not sharing common letters are significantly different (p < 0.05). ALT: alanine aminotransferase, AST: aspartate aminotransferase.