Overall assessment of antibiotic substitutes for pigs:a set of meta-analyses

Background:Antibiotic growth promoters are widely used to improve weight gain.However,the abuse of antibiotics can have many negative effects on people.Developing alternatives to antibiotics is an urgent need in livestock production.We aimed to perform a meta-analysis and network meta-analysis(NMA)to investigate the effects of feed additives as potential antibiotic substitutes(ASs)on bacteriostasis,growth performance,intestinal morphology and immunity.Furthermore,the primary,secondary,and tertiary ASs were defined by comparing their results with the results of antibiotics.Results:Among 16,309 identified studies,37 were summarized to study the bacteriostasis effects of feed additives,and 89 were included in the meta-analysis and NMA(10,228 pigs).We summarized 268 associations of 57 interventions with 32 bacteria.The order of bacteriostasis effects was as follows:antimicrobial peptides(AMPs)≈antibiotics>organic acids>plant extracts>oligosaccharides.We detected associations of 11 feed additives and 11 outcomes.Compared with a basal diet,plant extract,AMPs,probiotics,microelements,organic acids,bacteriophages,lysozyme,zymin,and oligosaccharides significantly improved growth performance(P<0.05);organic acids,probiotics,microelements,lysozyme,and AMPs remarkably increased the villus height:crypt depth ratio(V/C)(P<0.05);and plant extracts,zymin,microelements,probiotics,and organic acids notably improved immunity(P<0.05).The optimal AMP,bacteriophage,lysozyme,microelements,oligosaccharides,organic acids,plants,plant extracts,probiotics,and zymin doses were 0.100%,0.150%,0.012%,0.010%,0.050%,0.750%,0.20%,0.040%,0.180%,and 0.100%,respectively.Compared with antibiotics,all investigated feed additives exhibited no significant difference in effects on growth performance,IgG,and diarrhoea index/rate(P>0.05);AMPs and microelements significantly increased V/C(P<0.05);and zymin significantly improved lymphocyte levels(P<0.05).Furthermore,linear weighting sum models were used to comprehensively estimate the overall impact of each feed additive on pig growth and health.Conclusions:Our findings suggest that AMPs and plant extracts can be used as primary ASs for weaned piglets and growing pigs,respectively.Bacteriophages,zymin,plants,probiotics,oligosaccharides,lysozyme,and microelements can be regarded as secondary ASs.Nucleotides and organic acids can be considered as tertiary ASs.Future studies should further assess the alternative effects of combinational feed additives.

Effects of long-chain fatty acid supplementation on the growth performance of grower and finisher pigs: a meta-analysis

Background: Supplementation of feed with long-chain fatty acids(LCFAs) during the grower and finisher phases has long been discussed as a growth promotion strategy in pigs, but its effects are inconsistent. The purpose of our study was to comprehensively evaluate its effects on the growth performance based on the average daily gain(ADG), average daily feed intake(ADFI) and gain: feed(G:F) ratio and to unveil the roles of the basal diet, LCFA concentration and LCFA saturation.Results: We searched the Pub Med and Web of Science databases(articles published from Jan 1 st, 2000, to Sep 30 th,2018;restricted to English) and compared LCFA-supplemented diets with control diets. We retrieved 2346 studies, 18 of which(1314 pigs, 26 records) were eligible for our analysis. We used a random-effects model to calculate the weighted mean differences(WMDs) and 95% confidence intervals(CIs). LCFA supplementation in the grower-finisher phase improved the ADG(WMD = 41.74 g/d, 95% CI: 8.81 to 74.66, P = 0.013) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P = 0.003). For supplementation solely in the finisher phase, we found a similar performance in the ADG(WMD = 39.93 g/d, 95% CI: 26.48 to 53.38, P < 0.001) and G:F ratio(WMD = 0.019, 95% CI: 0.006 to 0.032, P < 0.001) but a reduction in the ADFI(WMD =-83.863 g/d, 95% CI:-156.157 to-11.569, P = 0.023). Specifically, approximately 5%LCFA supplementation in the finisher phase had significant effects on the ADG(WMD = 51.385 g/d, 95% CI: 35.816 to66.954, P < 0.001), ADFI(WMD =-102.869 g/d, 95% CI:-189.236 to-16.502, P = 0.02) and G:F ratio(WMD = 0.028, 95%CI: 0.018 to 0.039, P < 0.001), whereas a concentration of approximately 1% exhibited no effects.Conclusions: Overall, regardless of the basal diet and saturation, LCFA supplementation greatly improves the growth performance of grower and finisher pigs, primarily by increasing the energy density.

RCAN family member 3 deficiency contributes to noncompaction of the ventricular myocardium

Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular recesses.However,the genetic etiology of 40%–60%of NVM cases remains unknown.Here,we identify two infants with NVM,in a nonconsanguineous family,with a typical clinical presentation of persistent bradycardia since the prenatal period.A homozygous missense variant(R223L)of RCAN family member 3(RCAN3)is detected in both infants using whole-exome sequencing.In the zebrafish model,marked cardiac dysfunction is detected in rcan3 deficiency(MO-rcan3ATG-injected)and rcan−/−embryos.Developmental dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient embryos.RCAN3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout;however,hRCAN3 mRNAs rescue these phenotypes.RNA-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish model.In human cardiomyocytes,RCAN3 deficiency results in reduced proliferation and increased apoptosis,together with an abnormal mitochondrial ultrastructure.Thus,we suggest that RCAN3 is a susceptibility gene for cardiomyopathies,especially NVM and that the R223L mutation is a potential loss-of-function variant.

Interplay between gut microbiota and antimicrobial peptides

The gut microbiota is comprised of a diverse array of microorganisms that interact with immune system and exert crucial roles for the health.Changes in the gut microbiota composition and functionality are associated with multiple diseases.As such,mobilizing a rapid and appropriate antimicrobial response depending on the nature of each stimulus is crucial for maintaining the balance between homeostasis and inflammation in the gut.Major players in this scenario are antimicrobial peptides(AMP),which belong to an ancient defense system found in all organisms and participate in a preservative co-evolution with a complex microbiome.Particularly increasing interactions between AMP and microbiota have been found in the gut.Here,we focus on the mechanisms by which AMP help to maintain a balanced microbiota and advancing our understanding of the circumstances of such balanced interactions between gut microbiota and host AMP.This review aims to provide a comprehensive overview on the interplay of diverse antimicrobial responses with enteric pathogens and the gut microbiota,which should have therapeutic implications for different intestinal disorders.