| Due to global warming,the effects of heat stress(HS)on livestock production are increasing.Because of the lack of sweat glands and breed selection,sows have lower thermal comfort temperature zone and higher basic metabolic heat load and are more sensitive to HS.HS can change the metabolic profiles and carcass quality of suckling piglets by affecting the performance and metabolic profiles of lactating sows.Additionally,HS can damage the intestinal barrier function,resulting in increased intestinal permeability,promoting an inflammatory response of the body and reducing its production performance.Late gestation is a critical period for fetal growth,development,and milk production during lactation.However,there is very limited systematic research on the effects of HS on pregnant sows.It is unclear whether late gestational HS will change the metabolic profiles of sows as well as intestinal microbiota and their metabolites.Besides,late gestation is also a vital period for maternal microbial transmission and microbial colonization for offspring.The effects of late gestational HS on maternal microbial transmission is also unknown.Moreover,the mitochondrion is called the"power factory" of the cell,and its inner membrane respiratory chain is the main place where ATP is produced by oxidative phosphorylation of the cell.Given its important role in energy metabolism,liver mitochondrial function and its relationship with maternal metabolism and intestinal microbiota under late gestational heat stress are worth further discussion.Therefore,this study involved pregnant sows and mice to evaluate the effects of HS during late gestation on maternal metabolism and intestinal microbiota.Meanwhile,by using sows and mice model,we preliminarily explored the maternal microbial transmission during late gestational HS and the relationship among liver mitochondrial function and host metabolism and intestinal microbiota,respectively.1 A controlled heat stress during late gestation affects thermoregulation,productive performance,and metabolic profiles of primiparous sowWe present here,a study investigating the productive performance and metabolic responses in sows when exposed to HS during late gestation.Twelve first-parity Landrace ×Large White F1 sows were randomly assigned into two environmental treatments including the thermoneutral(TN)(19-22℃;n=6)and HS(29-32℃;n=6)conditions from 85 d of gestation until farrowing.Rectal temperature(RT),respiration rates(RR),and surface temperature(ST)were measured every 4 h from 0800h to 2000h during the 2nd week.Farrowing and litter Data,as well as duration of eating,were monitored to assess sows’productive performance.Blood biochemical parameters and urinary metabolomic profiles were measured on d107 of gestation to analyze the host metabolic responses.Our results show that HS increased RT,RR,and ST(P<0.0001).Duration of parturition was prolonged during the delivery in HS group(P<0.05).Piglet body weight(BW)at d 10 and weaning were reduced by 18%and 17%respectively due to maternal HS(P<0.001).Moreover,serum ACTH,cortisol,insulin,creatinine,and BUN saw increase as well(P<0.05).Plasma NEFA were elevated by HS(P<0.001).Additionally,HS elevated the pantothenate and CoA biosynthesis,β-alanine metabolism,and glycerolipid metabolism in pregnant sows.In summary,our study suggests that the controlled HS during late gestation elevates thermal responses,reduces productive performance,and more importantly,enhances the catabolism of lipid and protein of first-parity pregnant sow.2 Heat stress affects fecal microbial and metabolic alterations of primiparous sow during late gestationWe present here,a study investigating the fecal microbial and metabolic responses in late gestational primiparous sows when exposed to HS.The experimental design was the same as in the first chapter.The serum and feces samples were collected on d 107 of gestation,for analyses including intestinal integrity biomarkers,high-throughput sequencing metagenomics,short-chain fatty acid(SCFA)profiles and nontargeted metabolomics.Our results show that HS group has higher serum Heat shock protein 70(HSP70),lipopolysaccharide(LPS)and lipopolysaccharide-binding protein(LBP)levels.The gut microbial community can be altered upon HS by using β-diversity and taxon-based analysis.In particular,the relative abundance of genera and operational taxonomic units(OTU)related to Clostridiales and Halomonas are higher in HS group,the relative abundance of genera and OTU related to Bacteroidales and Streptococcus,however,are lower in HS group.Results of metabolic analysis reveal that HS lowers the concentrations of propionate,butyrate,total SCFAs,succinate,fumarate,malate,lactate,aspartate,ethanolamine,β-alanine and niacin,whereas that of fructose and azelaic acid are higher in HS group.These metabolites mainly affect propanoate metabolism,alanine,aspartate and glutamate metabolism,phenylalanine metabolism,β-alanine metabolism,pantothenate and CoA biosynthesis,tricarboxylic acid cycle(TCA)and nicotinate and nicotinamide metabolism.Additionally,correlation analysis between significant microbes and metabolites indicated that the HS-induced microbiota shift is likely the cause of changes of intestinal metabolism.Taken together,we reveal characteristic structural and metabolic changes in maternal gut microbiota because of late gestational HS,which could potentially provide the basis for further study on offspring gut microbiota and immune programming.3 Heat stress during late gestation disrupts maternal microbial transmissions with altered offspring’s gut microbial colonization and serum metabolites in a pig modelWe present here,a study investigating maternal microbial composition and transmissions,as well as offspring’s intestinal microbial colonization and serum metabolic profiles of late gestational primiparous sows when exposed to HS.The experimental design was the same as in the first chapter.Sows’ fecal and vaginal samples were collected at 107d of gestation for bacterial 16S rDNA sequencing.One piglet per litter was selected for slaughter based on his/her average body weight,and their meconium and serum samples were also collected for bacterial 16S rDNA sequencing and serum metabolic profiles,respectively.Our results show maternal.HS tends to alter bacterial β-diversity and significantly changes bacterial compositions in sows and piglets.Moreover,the core OTU analysis indicates the proportions of Clostridium sensu stricto 1,Romboutsia and Turicibacter are decreased by maternal HS in the intestinal and vaginal co-transmission,whereas that of phylum Proteobacteria and Epsilonbacteraeota,such as Escherichia-Shigella,Klebsiella,Acinetobacter,and Comamonas are increased in both the intestinal and vaginal cotransmission and the vagina.Additionally,Aeromonas is the only genus that is transmitted from environmental sources.Lastly,we evaluate the importance of neonatal differential OTU for the differential serum metabolites.The results indicate Acinetobacter and Stenotrophomonas are the most important variables for differential serum metabolites.Overall,our data provides evidence for the maternal HS in establishing the neonatal microbiota via affecting maternal transmissions,which in turn affects the maintenance of metabolic health.4 Effect of heat stress during late gestation on physiological status,metabolic profiles,and mitochondrial function of pregnant miceHere,the first objective of this trial is to using mouse as model for verifying the effects of HS during late gestation on maternal physiological state(temperature,food intake,drinking water)and metabolic characteristics(body composition and serum biochemical indicators).Secondly,we aim to test the effects of HS on liver mitochondrial function and its contribution to differential metabolites.Twenty ICR female mice that were bred on the same day were randomly were randomly assigned into two environmental treatments including the thermoneutral(TN)(24±1℃;n=10)and HS(35±1℃;n=8)conditions from 12 d of gestation until farrowing.After pregnancy was determined,rectal temperature,food intake and water consumption were measured daily.Moreover,serum,liver,and carcass samples were collected from mice at 18 d of gestation for measuring blood biochemical indicators,mRNA expression levels of mitochondrial function-related genes,and body fat and protein contents.The results showed that HS significantly increased serum levels of corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH),corticosterone,and HSP70(P<0.05).Also,HS significantly increased rectal temperature,water consumption,decreased feed intake,body fat and protein content(P<0.05).Moreover,HS remarkably reduced serum concentrations of insulin and triglyceride(TG),increased levels of glucagon,NEFA,and β-hydroxybutyric acid(B-HBA),creatinine,BUN,malondialdehyde(MDA),and 8-hydroxydeoxyguanosine(8-OHdG)(P<0.05).Additionally,HS notably reduced the mRNA expression levels of Mt-DNA encoding ND1,ND2,ND6,COX1,COX2,ATP6(P<0.01)and ND3,ND4L,ATP8(P<0.05).Meanwhile,the mRNA expression levels of nuclear coding UCP2,TFAM,CPT1α and CS were also decreased owing to HS(P<0.05).Lastly,random forest(RF)and multiple linear regression(MLR)analysis showed that the mRNA expression levels of liver mitochondrial function-related genes,especially ND4L and COX1,had significant contributions on changes in metabolic profiles.Overall,HS during late gestation indeed causes maternal physiological responses,and may reduce ATP synthesis by aggravating the damage of NADH dehydrogenase and cytochrome c oxidase in the mitochondrial respiratory chain,which in turn leads to insufficient energy supply and increasing breakdown of fat and protein.5 Alterations of colonic microbiota during late gestation affects serum metabolites and liver mitochondrial function of pregnant miceThe experimental design of this study is the same as in the previous chapter.Mouse serum and colonic digesta samples were collected at 18 d of gestation for measuring blood biochemical indicators and bacteria 16S rDNA sequence.The results showed that HS during late gestation significantly increased serum LPS and LBP levels in mice(P<0.01).HS significantly altered colonic microbial β-diversity(ANOSIM,P<0.01)and composition,with increasing relative abundance of Escherichia-Shigella,Acinetobacter and Klebsiella related OTU(P<0.05),while reducing the proportions of Ruminiclostridium,Blautia,Lachnospiraceae_NK4A 136-group,Clostridium VadinBB60 family and Muribacaceae related OTU(P<0.05).Moreover,PICRUSt analysis indicated that HS significantly upregulated 11 KEGG level 3 pathways,including Bile secretion,and Bacterial invasion of epithelial cells and so on.Lastly,RF and MLR analysis showed that the differential colonic bacteria,especially Ruminiclostridium,Klebsiella and Escherichia-Shigella,had significant contributions on the differential serum metabolic indicators and mRNA relative expression of liver mitochondrial functional gene.Overall,HS during late gestation significantly alters the β-diversity and composition of colonic microbiota.This microbial dysbiosis causes disrupted microbial metabolites,and further activates the HPA axis,enhances fat and protein catabolism,stimulates inflammatory response and damages mitochondrial function. |
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