Background: Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, ...Background: Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, proline is known to play important roles in protein metabolism and structure, cell differentiation, conceptus growth and development, and gut microbiota re-equilibration in case of dysbiosis.Results: Dietary supplementation with 1% proline decreased(P < 0.05) the amounts of Klebsiella pneumoniae,Peptostreptococcus productus, Pseudomonas, and Veillonella spp. in distal colonic contents than that in the control group. The colonic contents of Butyrivibrio fibrisolvens, Bifidobacterium sp., Clostridium coccoides, Clostridium coccoides-Eubacterium rectale, Clostridium leptum subgroup, Escherichia coli, Faecalibacterium prausnitzii,Fusobacterium prausnitzii, and Prevotella increased(P < 0.05) on d 70 of pregnancy as compared with those on d 45 of pregnancy. The colonic concentrations of acetate, total straight-chain fatty acid, and total short-chain fatty acids(SCFA) in the proline-supplemented group were lower(P < 0.05), and butyrate level(P = 0.06) decreased as compared with the control group. Almost all of the SCFA displayed higher(P < 0.05) concentrations in proximal colonic contents on d 70 of pregnancy than those on d 45 of pregnancy. The concentrations of 1,7-heptyl diamine(P = 0.09) and phenylethylamine(P < 0.05) in proximal colonic contents were higher, while those of spermidine(P = 0.05) and total bioamine(P = 0.06) tended to be lower in the proline-supplemented group than those in the control group. The concentrations of spermidine, spermine, and total bioamine in colonic contents were higher(P < 0.05) on d 70 of pregnancy than those measured on d 45 of pregnancy. In contrast, the concentration of phenylethylamine was lower(P < 0.05) on d 70 than on d 45 of pregnancy.(Continued on next page)(Continued from previous page)Conclusion: These findings indicate that L-proline supplementation modifies both the colonic microbiota composition and the luminal concentrations of several bacterial metabolites. Furthermore, our data show that both the microbiota composition and the concentrations of bacterial metabolites are evolving in the course of pregnancy. These results are discussed in terms of possible implication in terms of luminal environment and consequences for gut physiology and health.展开更多
Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction(IUGR).Results: Growth p...Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction(IUGR).Results: Growth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight(NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight(BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide(PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum;in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum;in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum;and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum.Spearman's correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.Conclusions: Growing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes,Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbiota intervention in growing-finishing IUGR pigs.展开更多
BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as ...BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.展开更多
Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study ex...Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.展开更多
Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metaboli...Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.展开更多
基金jointly supported by grants from the National Nature Science Foundation of China(31572421 and 31270044)National Key R&D Program(2017YFD0500503)“Western Light”key program for Talent Cultivation from Chinese Academy of Sciences,and Chinese Academy of Sciences Visiting Professorship for Senior International Scientists(F.Blachier,2013T2S0014)
文摘Background: Pregnancy is associated with important changes in gut microbiota composition. Dietary factors may affect the diversity, composition, and metabolic activity of the intestinal microbiota. Among amino acids, proline is known to play important roles in protein metabolism and structure, cell differentiation, conceptus growth and development, and gut microbiota re-equilibration in case of dysbiosis.Results: Dietary supplementation with 1% proline decreased(P < 0.05) the amounts of Klebsiella pneumoniae,Peptostreptococcus productus, Pseudomonas, and Veillonella spp. in distal colonic contents than that in the control group. The colonic contents of Butyrivibrio fibrisolvens, Bifidobacterium sp., Clostridium coccoides, Clostridium coccoides-Eubacterium rectale, Clostridium leptum subgroup, Escherichia coli, Faecalibacterium prausnitzii,Fusobacterium prausnitzii, and Prevotella increased(P < 0.05) on d 70 of pregnancy as compared with those on d 45 of pregnancy. The colonic concentrations of acetate, total straight-chain fatty acid, and total short-chain fatty acids(SCFA) in the proline-supplemented group were lower(P < 0.05), and butyrate level(P = 0.06) decreased as compared with the control group. Almost all of the SCFA displayed higher(P < 0.05) concentrations in proximal colonic contents on d 70 of pregnancy than those on d 45 of pregnancy. The concentrations of 1,7-heptyl diamine(P = 0.09) and phenylethylamine(P < 0.05) in proximal colonic contents were higher, while those of spermidine(P = 0.05) and total bioamine(P = 0.06) tended to be lower in the proline-supplemented group than those in the control group. The concentrations of spermidine, spermine, and total bioamine in colonic contents were higher(P < 0.05) on d 70 of pregnancy than those measured on d 45 of pregnancy. In contrast, the concentration of phenylethylamine was lower(P < 0.05) on d 70 than on d 45 of pregnancy.(Continued on next page)(Continued from previous page)Conclusion: These findings indicate that L-proline supplementation modifies both the colonic microbiota composition and the luminal concentrations of several bacterial metabolites. Furthermore, our data show that both the microbiota composition and the concentrations of bacterial metabolites are evolving in the course of pregnancy. These results are discussed in terms of possible implication in terms of luminal environment and consequences for gut physiology and health.
基金jointly supported by the National Natural Science Foundation of China (31772613 and 31572421)Special Funds for Construction of Innovative Provinces in Hunan Province (2019RS3022)。
文摘Background: The interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction(IUGR).Results: Growth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight(NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight(BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide(PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum;in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum;in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum;and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum.Spearman's correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.Conclusions: Growing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes,Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbiota intervention in growing-finishing IUGR pigs.
基金grants from the Societe Francaise de Nutrition and the Association Francois AupetitVidal-Lletjos S was a recipient of a PhD grant from INRA-Universite Paris-Saclay(ALIAS program)
文摘BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.
基金the Key Project of Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(U20A2056)the Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022).
文摘Background Intrauterine growth retardation(IUGR)is one of the major constraints in animal production.Our previ-ous study showed that piglets with IUGR are associated with abnormal bile acid(BA)metabolism.This study explored whether dietary BA supplementation could improve growth performance and colonic development,function,micro-biota,and metabolites in the normal birth weight(NBW)and IUGR piglets.A total of 48 weaned piglets(24 IUGR and 24 NBW)were allocated to four groups(12 piglets per group):(i)NBW group,(ii)NBW+BA group,(iii)IUGR group,and(iv)IUGR+BA group.Samples were collected after 28 days of feeding.Results The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio,while decreased the plasma diamine oxidase(DAO)concentration in the NBW pig-lets(P<0.05).Dietary BA supplementation to IUGR piglets decreased(P<0.05)the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin,suggesting a beneficial effect on epithelial integrity.Moreover,dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance(P<0.05),whereas Lactobacillus was the dominant genus in the colon.Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA,respectively,which was associated with the colonic function of IUGR piglets.Furthermore,dietary BA supplementation to IUGR piglets upregulated the expressions of CAT,GPX,SOD,Nrf1,IL-2,and IFN-γin colonic mucosa(P<0.05).Conclusions Collectively,dietary BA supplementation could improve the colonic function of IUGR piglets,which was associated with increasing proportions of potentially beneficial bacteria and metabolites.Furthermore,BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.
基金supported by the National Natural Science Foundation of China(U20A2056)Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022).
文摘Background:Intrauterine growth retardation(IUGR)is associated with severely impaired nutrient metabolism and intestinal development of pigs.Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon.However,the consequences of IUGR on bile acid metabolism in pigs remained unclear.The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of grow-ing pigs with IUGR using bile acid targeted metabolomics.Furthermore,we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight(NBW)pigs at different growth stages that were 7,21,and 28-day-old,and the average body weight(BW)of 25,50,and 100 kg of the NBW pigs.Results:The results showed that the plasma total bile acid concentration was higher(P<0.05)at the 25 kg BW stage and tended to increase(P=0.08)at 28-day-old in IUGR pigs.The hepatic gene expressions related to bile acid synthe-sis(CYP7A1,CYP27A1,and NTCP)were up-regulated(P<0.05),and the genes related to glucose and lipid metabolism(ATGL,HSL,and PC)were down-regulated(P<0.05)at the 25 kg BW stage in IUGR pigs when compared with the NBW group.Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs.The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased(P<0.05),while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased(P<0.05)in IUGR pigs,when compared with the NBW pigs at the 25 kg BW stage.Moreover,Spearman’s correlation analysis revealed that colonic Unclassified_[Mogi-bacteriaceae],Lachnospira,and Slackia abundances were negatively correlated(P<0.05)with dehydrolithocholic acid,as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage.Conclusions:These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs,especially at the 25 kg BW stage,these effects being paralleled by a modification of bile acid derivatives concentra-tions in the colonic content.The plausible links between these modified parameters are discussed.
