Gut microbes,particularly those in the hindgut,play an important role in fermenting undigested nutrients(carbohydrates and proteins)and in regulating host metabolism via the gut-liver metabolic axis.However,the effect...Gut microbes,particularly those in the hindgut,play an important role in fermenting undigested nutrients(carbohydrates and proteins)and in regulating host metabolism via the gut-liver metabolic axis.However,the effects of variations in the ratio of carbohydrates to proteins on host metabolism remain largely unknown.This study investigated the response of large intestinal microbiota and host metabolism to changes in nutrient substrate availability by infusing corn starch or casein hydrolysate via cecal cannulas.Twenty-four growing pigs with cecal cannulas were randomly divided into three groups(n=8):a control group infused with saline;a starch group infused with corn starch;and a casein group infused with casein hydrolysate(50 g/d)dissolved in saline.The infusion was performed daily for 19 d.Compared with the control,starch infusion significantly increased the relative abundances of Bifidobacterium,Bacteroidales S24-7 group and Megasphaera(P<0.05),while decreasing Anaerovibrio,Campylobacter and Veillonella(P<0.05).Conversely,casein hydrolysate infusion significantly increased Streptococcus,Desulfovibrio and Mogibacterium(P<0.05),while decreasing Coprococcus and Ruminococcus at the genus level(P<0.05).Starch infusion increased short-chain fatty acid(SCFA)concentrations(P=0.001),whereas casein hydrolysate infusion reduced them(P=0.001);these effects were observed in both colonic digesta and liver.Additionally,serum metabolomics and liver gene expression analysis revealed that host metabolic states were significantly altered in different ways following starch and casein hydrolysate infusion(P<0.05).Starch infusion enhanced host energy metabolism,gluconeogenesis and lipid metabolism by increasing concentrations of tricarboxylic acid(TCA)cycle-related metabolites(e.g.,succinic acid,oxaloacetic acid,and L-malic acid)and fatty acid(FA)synthesis(e.g.,D-glyceric acid,stearic acid,and palmitic acid)(P<0.05),alongside upregulation of FA synthase(FAS),stearoyl-CoA desaturase(SCD),acetyl-CoA carboxylase(ACC),phosphoenolpyruvate carboxykinase 1(PCK1)and pyruvate kinase(PK)gene expression(P<0.05).In contrast,casein hydrolysate infusion enhanced glycolysis and reduced FA synthesis by increasing glucose-6-phosphate,L-lactic acid,glycerol,glycolic acid,etc.(P<0.05),in parallel with upregulation of acyl-CoA oxidase 1(ACOX-1),peroxisome proliferator-activated receptors α(PPAR-α),carnitine palmitoyltransferase-1α(CPT-1α)and PK gene expressions in the liver(P<0.05).Correlation result demonstrated a strong association between altered gut microbiota and several serum metabolites(P<0.05).In summary,these results indicate that increasing carbohydrate or nitrogenous compound levels in the large intestine can distinctly alter microbiota composition,thereby influencing host metabolism.These findings provide novel insights into the crosstalk between the large intestinal microbiome and host metabolism.展开更多
基金supported by grants from the National Natural Science Foundation of China(NSFC)(31430082)the National Key Basic Research Program of China(2013CB127300)the Natural Science Foundation of Jiangsu Province(BK20130058).
文摘Gut microbes,particularly those in the hindgut,play an important role in fermenting undigested nutrients(carbohydrates and proteins)and in regulating host metabolism via the gut-liver metabolic axis.However,the effects of variations in the ratio of carbohydrates to proteins on host metabolism remain largely unknown.This study investigated the response of large intestinal microbiota and host metabolism to changes in nutrient substrate availability by infusing corn starch or casein hydrolysate via cecal cannulas.Twenty-four growing pigs with cecal cannulas were randomly divided into three groups(n=8):a control group infused with saline;a starch group infused with corn starch;and a casein group infused with casein hydrolysate(50 g/d)dissolved in saline.The infusion was performed daily for 19 d.Compared with the control,starch infusion significantly increased the relative abundances of Bifidobacterium,Bacteroidales S24-7 group and Megasphaera(P<0.05),while decreasing Anaerovibrio,Campylobacter and Veillonella(P<0.05).Conversely,casein hydrolysate infusion significantly increased Streptococcus,Desulfovibrio and Mogibacterium(P<0.05),while decreasing Coprococcus and Ruminococcus at the genus level(P<0.05).Starch infusion increased short-chain fatty acid(SCFA)concentrations(P=0.001),whereas casein hydrolysate infusion reduced them(P=0.001);these effects were observed in both colonic digesta and liver.Additionally,serum metabolomics and liver gene expression analysis revealed that host metabolic states were significantly altered in different ways following starch and casein hydrolysate infusion(P<0.05).Starch infusion enhanced host energy metabolism,gluconeogenesis and lipid metabolism by increasing concentrations of tricarboxylic acid(TCA)cycle-related metabolites(e.g.,succinic acid,oxaloacetic acid,and L-malic acid)and fatty acid(FA)synthesis(e.g.,D-glyceric acid,stearic acid,and palmitic acid)(P<0.05),alongside upregulation of FA synthase(FAS),stearoyl-CoA desaturase(SCD),acetyl-CoA carboxylase(ACC),phosphoenolpyruvate carboxykinase 1(PCK1)and pyruvate kinase(PK)gene expression(P<0.05).In contrast,casein hydrolysate infusion enhanced glycolysis and reduced FA synthesis by increasing glucose-6-phosphate,L-lactic acid,glycerol,glycolic acid,etc.(P<0.05),in parallel with upregulation of acyl-CoA oxidase 1(ACOX-1),peroxisome proliferator-activated receptors α(PPAR-α),carnitine palmitoyltransferase-1α(CPT-1α)and PK gene expressions in the liver(P<0.05).Correlation result demonstrated a strong association between altered gut microbiota and several serum metabolites(P<0.05).In summary,these results indicate that increasing carbohydrate or nitrogenous compound levels in the large intestine can distinctly alter microbiota composition,thereby influencing host metabolism.These findings provide novel insights into the crosstalk between the large intestinal microbiome and host metabolism.
