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The probiotic Bacillus subtilis 29784 (Bs29784) sustains chicken's intestinal health, enhancing animal resilience and performance through the production of the bioactive metabolites hypoxanthine (HPX), niacin (NIA), and pantothenate (PTH). Here, using enterocyte in vitro models, we determine the functional link between these metabolites and the three pillars of intestinal resilience: immune response, intestinal barrier, and microbiota. We evaluated in vitro the capacity of Bs29784 vegetative cells, spores, and metabolites to modulate global immune regulators (using HT-29-NF-κB and HT-29-AP-1 reporter cells), intestinal integrity (HT-29-MUC2 reporter cells and Caco-2 cells), and cytokine production (Caco-2 cells). Finally, we simulated intestinal fermentations using chicken's intestinal contents as inocula to determine the effect of Bs29784 metabolites on the microbiota and their fermentation profile. Bs29784 vegetative cells reduced the inflammatory response more effectively than spores, indicating that their benefit is linked to metabolic activity. To assess this hypothesis, we studied Bs29784 metabolites individually. The results showed that each metabolite had different beneficial effects. PTH and NIA reduced the activation of the pro-inflammatory pathways AP-1 and NF-κB. HPX upregulated mucin production by enhancing MUC2 expression. HPX, NIA, and PTH increased cell proliferation. PTH and HPX increased epithelial resilience to an inflammatory challenge by limiting permeability increase. In cecal fermentations, NIA increased acetate, HPX increased butyrate, whereas PTH increased acetate, butyrate, and propionate. In ileal fermentations, PTH increased butyrate. All molecules modulated microbiota, explaining the different fermentation patterns. Altogether, we show that Bs29784 influences intestinal health by acting on the three lines of resilience via its secreted metabolites. IMPORTANCE: Probiotics provide beneficial metabolites to its host. Here, we describe the mode of action of a commonly used probiotic in poultry, Bs29784. By using in vitro cellular techniques and simulated chickens' intestinal model, we show the functional link between Bs29784 metabolites and the three lines of animal resilience. Indeed, both Bs29784 vegetative cells and its metabolites stimulate cellular anti-inflammatory responses, strengthen intestinal barrier, and positively modulate microbiota composition and fermentative profile. Taken together, these results strengthen our understanding of the effect of Bs29784 on its host and explain, at least partly, its positive effects on animal health, resilience, and performance.

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Diet is a major modulator of animal resilience and its three pillars: host's immune response, gut microbiota, and intestinal barrier. In the present study, we endeavour to delineate a challenging condition aimed to degrade these pillars and elucidate its impact on broiler performance and nutrient digestibility. To attain this objective, we opted to use guar gum (GG) as a source of galactomannan. A series of three in vivo experiments were conducted employing conventional or semi-purified diets, supplemented with or without GG during the grower phase (14-28 d). Our findings demonstrate a substantial decline in animal performance metrics such as body weight (reduced by 29%, P < 0.001), feed intake (decreased by 12%, P < 0.001), and feed conversion ratio (up to 58% increase, P < 0.001) in the presence of GG at 2%. The supplementation of a semi-purified diet with incremental doses of GG resulted in a linear reduction (P < 0.001) in the apparent total tract digestibility of dry matter and apparent metabolisable energy. Additionally, a marked reduction in ileal endogenous losses, as well as apparent and standardised digestibility of all amino acids with varying proportions (P < 0.05), was observed. These alterations were accompanied by disrupted gut integrity assessed by fluorescein isothiocyanate-dextran (FITC-d) (P < 0.001) as well as an inflammatory status characterised by elevated levels of acute-phase proteins, namely orosomucoid and serum amyloid A in the sera (P = 0.03), and increased mRNA expression levels of IL-1, IL-6, IL-8, Inos, and K203 genes in the ileum, along with a decrease in IgA levels in the gut lumen (P < 0.05). Microbial ecology and activity were characterised by reduced diversity and richness (Shannon index, P = 0.005) in the presence of GG. Consequently, our results revealed diminished levels of short-chain fatty acids (P = 0.01) and their producer genera, such as Clostridium_XIVa and Blautia, in the gut caeca, coupled with excessive accumulation of lactate (17-fold increase, P < 0.01) in the presence of GG at 2%. In addition to providing a more comprehensive characterisation of the GG supplementation as a leaky gut model, our results substantiate a thorough understanding of the intricate adjustments and interplay between the intestinal barrier, immune response, and microbiota. Furthermore, they underscore the significance of feed components in modulating these dynamics.

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Considering the increasing challenges imposed by climate change and the need to improve animal welfare, breeding more resilient animals capable of better coping with environmental disturbances is of paramount importance. In dairy cattle, resilience can be evaluated by measuring the longitudinal occurrences of abnormal daily milk yield throughout lactation. Aiming to estimate genetic parameters for dairy cattle resilience, we collected 5,643,193 daily milk yield records on automatic milking systems (milking robots) and milking parlors across 21,350 lactations 1 to 3 of 11,787 North American Holstein cows. All cows were genotyped with 62,029 SNPs. After determining the best fitting models for each of the 3 lactations, daily milk yield residuals were used to derive 4 resilience indicators: weighted occurrence frequency of yield perturbations (wfPert), accumulated milk losses of yield perturbations (dPert), and log-transformed variance (LnVar) and lag-1 autocorrelation (rauto) of daily yield residuals. The indicator LnVar presented the highest heritability estimates (±standard error), ranging from 0.13 ± 0.01 in lactation 1 to 0.15 ± 0.02 in lactation 2; the other 3 indicators had relatively lower heritabilities across the 3 lactations (0.01-0.06). Based on bivariate analyses of each resilience indicator across lactations, stronger genetic correlations were observed between lactations 2 and 3 (0.88-0.96) than between lactations 1 and 2 or 3 (0.34-0.88) for dPert, LnVar, and rauto. For the pairwise comparisons of different resilience indicators within each lactation, dPert had the strongest genetic correlations with wfPert (0.64) and rauto (0.53) in lactation 1, whereas the correlations in lactations 2 and 3 were more variable and showed relatively high standard errors. The genetic correlation results indicated that different resilience indicators across lactations might capture additional biological mechanisms and should be considered as different traits in genetic evaluations. We also observed favorable genetic correlations of these resilience indicators with longevity and Net Merit index, but further biological validation of these resilience indicators is needed. In conclusion, this study provided genetic parameter estimates for different resilience indicators derived from daily milk yields across the first 3 lactations in Holstein cattle, which will be useful when potentially incorporating these traits in dairy cattle breeding schemes.

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BACKGROUND: Pig production has been highlighted as one of the highest users of antibiotics amongst livestock, with several studies suggesting a variety of approaches to antibiotic reduction. We aimed to investigate links between antibiotic use (defined as total amount of critically (CIA) and non-critically important antibiotics, and as mg per kg of pig on farm), production stages present on farm (Breeder-Finisher, Nursery-Finisher, and Finisher), and pig farm characteristics using farm data collected through national recording systems in Great Britain for 2017 & 2018. Providing enrichment within pig pens may reduce the need for antibiotics by enhancing both pig welfare and resilience to infection; this was one of the hypotheses addressed by this paper. RESULTS: The amount of antibiotic used, expressed as mg/kg, reduced between 2017 and 2018 for Breeder-Finisher farms, but not for Nursery-Finisher or Finisher farms. Breeder-Finisher farms were more likely to use CIA compared with other production stages. Larger farms were more likely to use CIA, but farm size had no effect on mg/kg of antibiotic used. As the proportion of pens containing straw increased, the total use of antibiotics decreased for Breeder-Finisher, but not for Nursery-Finisher or Finisher farms. As the proportion of pens containing straw increased, the probability of using CIAs also decreased. Farms with a higher proportion of finisher pens with an outdoor space had a lower use of non-critical antibiotics and lower probability of use of CIA. Farms with a higher proportion of pens with automatically controlled natural ventilation (ACNV) had lower total use of antibiotics, although ACNV had no effect on the probability of using CIA. CONCLUSIONS: We quantified the influence of farm characteristics on the consumption of antibiotics in pig farms in England. Our findings support the hypothesis that farm characteristics have an influence on antibiotic use within a system and suggest that this reflects the balance of effects on both animal resilience and disease challenge. Consistent with our hypothesis, provision of straw was associated with reduced antibiotic use. We also demonstrate the value of using secondary databases, although further structural improvements are required to facilitate effective database combination and ensure maximum information benefits can be realised.

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Genetic selection for improved climatic resilience is paramount to increase the long-term sustainability of high-producing dairy cattle, especially in face of climate change. Various physiological indicators, such as rectal temperature (RT), respiration rate score (RR), and drooling score (DS), can be used to genetically identify animals with more effective coping mechanisms in response to heat stress events. In this study, we investigated genetic parameters for RT, RR (score from 1-3), and DS (score from 1-3). Furthermore, we assessed the genetic relationship among these indicators and other economically important traits for the dairy cattle industry. After data editing, 59,265 (RT), 30,290 (RR), and 30,421 (DS) records from 13,592 lactating Holstein cows were used for the analyses. Variance components were estimated based on a multiple-trait repeatability animal model. The heritability ± standard error estimate for RT, RR, and DS was 0.06 ± 0.01, 0.04 ± 0.01, and 0.02 ± 0.01, respectively, whereas their repeatability was 0.19, 0.14, and 0.14, respectively. Moderate genetic correlations of RR with RT and DS (0.26 ± 0.11 and 0.25 ± 0.16) and nonsignificant correlation between RT and DS (-0.11 ± 0.14) were observed. Furthermore, the approximate genetic correlations between RT, RR, and DS with 12 production, 29 conformation, 5 fertility and reproduction, 5 health, and 9 longevity-indicator traits were assessed. In general, the approximate genetic correlations calculated were low to moderate. In summary, 3 physiological indicators of heat stress response were measured in a large number of animals and shown to be lowly heritable. There is a value in developing a selection index including all the 3 indicators to improve heat tolerance in dairy cattle. All the unfavorable genetic relationships observed between heat tolerance and other economically important traits can be accounted for in a selection index to enable improved climatic resilience while also maintaining or increasing productivity in Holstein cattle.

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Heat stress is a major cause of welfare issues and economic losses to the worldwide dairy cattle industry. Genetic selection for heat tolerance has a great potential to positively affect the dairy industry, as the gains are permanent and cumulative over generations. Rectal temperature (RT) is hypothesized to be a good indicator trait of heat tolerance. Therefore, this study investigated the genetic architecture of RT by estimating genetic parameters, performing genome-wide association studies, and biologically validating potential candidate genes identified to be related to RT in Holstein cattle. A total of 33,013 RT records from 7,598 cows were used in this study. In addition, 1,114 cows were genotyped using the Illumina 150K Bovine BeadChip (Illumina, San Diego, CA). Rectal temperature measurements taken in the morning (AMRT) and in the afternoon (PMRT) are moderately heritable traits, with estimates of 0.09 ± 0.02 and 0.04 ± 0.01, respectively. These 2 traits are also highly genetically correlated (r = 0.90 ± 0.08). A total of 10 SNPs (located on BTA3, BTA4, BTA8, BTA13, BTA14, and BTA29) were found to be significantly associated with AMRT and PMRT. Subsequently, gene expression analyses were performed to validate the key functional genes identified (SPAG17, FAM107B, TSNARE1, RALYL, and PHRF1). This was done through in vitro exposure of peripheral blood mononuclear cells (PBMC) to different temperatures (37°C, 39°C, and 42°C). The relative mRNA expression of 2 genes, FAM107B and PHRF1, significantly changed between the control and heat stressed PBMC. In summary, RT is heritable, and enough genetic variability exists to enable genetic improvement of heat tolerance in Holstein cattle. Important genomic regions were identified and biologically validated; FAM107B and PHRF1 are the main candidate genes identified to influence heat stress response in dairy cattle.

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Intense selection for milk yield has increased environmental sensitivity in animals, and currently, heat stress is an expensive problem in dairy farming. The objectives were to identify the best model for characterizing environmental sensitivity in Holstein cattle, using the test-day milk yield (TDMY) combined with the temperature-humidity index (THI), and identify sires genetically superior for heat-stress (HS) tolerance and milk yield, through random regression. The data comprised 94,549 TDMYs of 11,294 first-parity Holstein cows in Brazil, collected from 1997 to 2013. The yield data were fitted to Legendre orthogonal polynomials, linear splines and the Wilmink function. The THI (the average of two days before the dairy control) was used as an environmental gradient. An animal model that fitted production using a Legendre polynomials of quartic order for the days in milk and quadratic equations for the THI presented a better quality of fit (Akaike's information criterion (AIC) and Bayesian information criterion (BIC)). The Spearman correlation coefficient of greatest impact was 0.54, between the top 1% for TDMY and top 1% for HS. Only 9% of the sires showed plasticity and an aptitude for joint selection. Thus, despite the small population fraction allowed for joint selection, sufficient genetic variability for selecting more resilient sires was found, which promoted concomitant genetic gains in milk yield and thermotolerance.

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Improving swine climatic resilience through genomic selection has the potential to minimize welfare issues and increase the industry profitability. The main objective of this study was to investigate the genetic and genomic determinism of tolerance to heat stress in four independent purebred populations of swine. Three female reproductive traits were investigated: total number of piglets born (TNB), number of piglets born alive (NBA) and average birth weight (ABW). More than 80,000 phenotypic and 12,000 genotyped individuals were included in this study. Genomic random-regression models were fitted regressing the phenotypes of interest on a set of 95 environmental covariates extracted from public weather station records. The models yielded estimates of (genomic) reactions norms for individual pigs, as indicator of heat tolerance. Heat tolerance is a heritable trait, although the heritabilities are larger under comfortable than heat-stress conditions (larger than 0.05 vs. 0.02 for TNB; 0.10 vs. 0.05 for NBA; larger than 0.20 vs. 0.10 for ABW). TNB showed the lowest genetic correlation (-38%) between divergent climatic conditions, being the trait with the strongest impact of genotype by environment interaction, while NBA and ABW showed values slightly negative or equal to zero reporting a milder impact of the genotype by environment interaction. After estimating genetic parameters, a genome-wide association study was performed based on the single-step GBLUP method. Heat tolerance was observed to be a highly polygenic trait. Multiple and non-overlapping genomic regions were identified for each trait based on the genomic breeding values for reproductive performance under comfortable or heat stress conditions. Relevant regions were found on chromosomes (SSC) 1, 3, 5, 6, 9, 11, and 12, although there were important regions across all autosomal chromosomes. The genomic region located on SSC9 appears to be of particular interest since it was identified for two traits (TNB and NBA) and in two independent populations. Heat tolerance based on reproductive performance indicators is a heritable trait and genetic progress for heat tolerance can be achieved through genetic or genomic selection. Various genomic regions and candidate genes with important biological functions were identified, which will be of great value for future functional genomic studies.

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Resilience is conceived as a dynamic developmental process involving the achievement of positive adaptation within the context of significant adversity. Resilience is not a unique ability but rather a set of capacities of a system put in place to absorb a disturbance and to reorganize while trying to retain the same function, structure, and identity. This review describes the characteristics and the molecular mechanisms of resilience to understand the core elements of resilience and its indicators. The objectives of this review are: (1) to define some of the leading environmental stressors and clarify the mechanism of vulnerability or resilience outcomes; (2) to clarify some of the prominent epigenetic modulations mediating resilience or vulnerability as a stress response; (3) to highlight the neural mechanisms related to stress resilience since the central nervous system is a highly dynamic structure characterized by an everlasting plasticity feature, which therefore has the opportunity to modify resilience. The review aims to introduce the reader to the concept of resilience seen as an ability acquired in life and not only inherited from birth.

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BACKGROUND: Climate change is expected to have a negative impact on food availability. While most efforts have been directed to reducing greenhouse gas emissions, complementary strategies are necessary to control the detrimental effects of climate change on farm animal performance. The objective of this study was to develop novel animal resilience phenotypes using reaction norm slopes, and examine their genetic and genomic parameters. A closely monitored dairy goat population was used for this purpose. RESULTS: Individual animals differed in their response to changing atmospheric temperature and a temperature-humidity index. Significant genetic variance and heritability estimates were derived for these animal resilience phenotypes. Furthermore, some resilience traits had a significant unfavourable genetic correlation with animal performance. Genome-wide association analyses identified several candidate genes related to animal resilience to environment change. CONCLUSIONS: Heritable variation exists among dairy goats in their production response to fluctuating weather variables. Results may inform future breeding programmes aimed to ensure efficient animal performance under changing climatic conditions.

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