84 research outputs found
Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery
Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers
are essential in the gut barrier maturation in the early life. The motherâofspring transmission of microorganisms is
the most important factor infuencing microbial colonization in mammals, and Câsection delivery (CSD) is an imporâ
tant disruptive factor of this transfer. Recently, the deregulation of symbiotic hostâmicrobe interactions in early life
has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and
infammation. The main goal of this study is to decipher the role of the earlyâlife gut microbiotaâbarrier alterations and
its links with laterâlife risks of intestinal infammation in a murine model of CSD.
Results The higher sensitivity to chemically induced infammation in CSD mice is related to excessive exposure to a
too diverse microbiota too early in life. This early microbial stimulus has shortâterm consequences on the host homeoâ
stasis. It switches the pupâs immune response to an infammatory context and alters the epithelium structure and
the mucusâproducing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early
life involves a disproportionate shortâchain fatty acids ratio and an excessive antigen exposure across the vulnerable
gut barrier in the frst days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the
microbiota is causal in the high sensitivity of CSD mice to chemicalâinduced colitis and in most of the phenotypical
parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by
CSD in mice, reverts the higher sensitivity to infammation in exâgermâfree mice colonized by CSD pupsâ microbiota.
Conclusions Earlyâlife gut microbiotaâhost crosstalk alterations related to CSD could be the linchpin behind the pheâ
notypic efects that lead to increased susceptibility to an induced infammation later in life in mice.
Keywords Câsection delivery, Microbiota, Primary colonization, Early life, Infammation, Gut barrier, Murine modelinfo:eu-repo/semantics/publishedVersio
Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery
Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother-offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD.
The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup's immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups' microbiota.
Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice
Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa
peer-reviewedSalmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogenâs ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection
Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa
[EN] Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen's ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infectionSIWe want to acknowledge the staff from the Genomics and Animal breeding group at the University of CĂłrdoba for their technical support to carry out this study. This article is based upon work from COST Action FA1401 (PiGutNet), supported by COST (European Cooperation in Science and Technology. This work was supported by the Spanish Ministry of Economy and Competitiveness (AGL2014-54089-R/AGL2017-87415-R). HA was funded by the PiGutNet COST action (FA1401) for a Short-Term Scientific Mission at INRAâs GABI laboratory (Jouy-en- Josas, France). SZL is a postdoctoral researcher supported by the Postdoctoral Trainee Program of the Spanish Ministry of Economy and Competitiveness (FPDI-2013-15619). HA is a postdoctoral researcher supported by the Juan de la Cierva Postdoctoral Trainee Program of the Spanish Ministry of Economy and Competitiveness (FJCI-2014-22877
Diversity across major and candidate genes in European local pig breeds
The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo-Calabrese, Basque, BĂsara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, Krskopolje (Krskopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, Schwa-bisch-Hallisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the populationâs structure and relationships
The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild
Background The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas. Results We successfully identified the causal genetic variant for SnowflakeÂżs albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that SnowflakeÂżs parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla. Conclusions In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost. Keywords: Gorilla; Albinism; Inbreeding; Genome; Conservatio
Diversity across major and candidate genes in European local pig breeds
The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo-Calabrese, Basque, BĂsara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, KrĆĄkopolje (KrĆĄkopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, SchwĂ€bisch-HĂ€llisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the population's structure and relationships
Genomic diversity, linkage disequilibrium and selection signatures in European local pig breeds assessed with a high density SNP chip
Genetic characterization of local breeds is essential to preserve their genomic variability, to advance
conservation policies and to contribute to their promotion and sustainability. Genomic diversity of
twenty European local pig breeds and a small sample of Spanish wild pigs was assessed using high
density SNP chips. A total of 992 DNA samples were analyzed with the GeneSeek Genomic Profler
(GGP) 70K HD porcine genotyping chip. Genotype data was employed to compute genetic diversity,
population diferentiation and structure, genetic distances, linkage disequilibrium and efective
population size. Our results point out several breeds, such as Turopolje, Apulo Calabrese, Casertana,
Mora Romagnola and Lithuanian indigenous wattle, having the lowest genetic diversity, supported
by low heterozygosity and very small efective population size, demonstrating the need of enhanced
conservation strategies. Principal components analysis showed the clustering of the individuals of
the same breed, with few breeds being clearly isolated from the rest. Several breeds were partially
overlapped, suggesting genetic closeness, which was particularly marked in the case of Iberian and
Alentejana breeds. Spanish wild boar was also narrowly related to other western populations, in
agreement with recurrent admixture between wild and domestic animals. We also searched across
the genome for loci under diversifying selection based on FST outlier tests. Candidate genes that may
underlie diferences in adaptation to specifc environments and productive systems and phenotypic
traits were detected in potentially selected genomic regions.FE1B-06B2-126F | JosĂ© Pedro Pinto de AraĂșjoN/
Genome-wide association study confirm major QTL for backfat fatty acid composition on SSC14 in Duroc pigs
Background: Fatty acid composition contributes importantly to meat quality and is essential to the nutritional
value of the meat. Identification of genetic factors underlying levels of fatty acids can be used to breed for pigs
with healthier meat. The aim of this study was to conduct genome-wide association studies (GWAS) to identify QTL
regions affecting fatty acid composition in backfat from the pig breeds Duroc and Landrace.
Results: Using data from the Axiom porcine 660 K array, we performed GWAS on 454 Duroc and 659 Landrace
boars for fatty acid phenotypes measured by near-infrared spectroscopy (NIRS) technology (C16:0, C16:1n-7, C18:0,
C18:1n-9, C18:2n-6, C18:3n-3, total saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty
acids). Two QTL regions on SSC4 and SSC14 were identified in Duroc for the de novo synthesized fatty acids traits,
whereas one QTL on SSC8 was detected in Landrace for C16:1n-7. The QTL region on SSC14 has been reported in
previous studies and a putative causative mutation has been suggested in the promoter region of the SCD gene.
Whole genome re-sequencing data was used for genotype imputation and to fine map the SSC14 QTL region in
Norwegian Duroc. This effort confirms the location of the QTL on this chromosome as well as suggesting other
putative candidate genes in the region. The most significant single nucleotide polymorphisms (SNPs) located on
SSC14 explain between 55 and 76% of the genetic variance and between 27 and 54% of the phenotypic variance
for the de novo synthesized fatty acid traits in Norwegian Duroc. For the QTL region on SSC8 in Landrace, the most
significant SNP explained 19% of the genetic variance and 5% of the phenotypic variance for C16:1n-7.
Conclusions: This study confirms a major QTL affecting fatty acid composition on SSC14 in Duroc, which can be
used in genetic selection to increase the level of fatty acid desaturation. The SSC14 QTL was not segregating in the
Landrace population, but another QTL on SSC8 affecting C16:1n-7 was identified and might be used to increase the
level of desaturation in meat products from this breed
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