Social environment influences microbiota and potentially pathogenic bacterial communities on the skin of developing birds.

BACKGROUND: Animal bacterial symbionts are established early in life, either through vertical transmission and/or by horizontal transmission from both the physical and the social environment, such as direct contact with con- or heterospecifics. The social environment particularly can influence the acquisition of both mutualistic and pathogenic bacteria, with consequences for the stability of symbiotic communities. However, segregating the effects of the shared physical environment from those of the social interactions is challenging, limiting our current knowledge on the role of the social environment in structuring bacterial communities in wild animals. Here, we take advantage of the avian brood-parasite system of Eurasian magpies (Pica pica) and great spotted cuckoos (Clamator glandarius) to explore how the interspecific social environment (magpie nestlings developing with or without heterospecifics) affects bacterial communities on uropygial gland skin. RESULTS: We demonstrated interspecific differences in bacterial community compositions in members of the two species when growing up in monospecific nests. However, the bacterial community of magpies in heterospecific nests was richer, more diverse, and more similar to their cuckoo nest-mates than when growing up in monospecific nests. These patterns were alike for the subset of microbes that could be considered core, but when looking at the subset of potentially pathogenic bacterial genera, cuckoo presence reduced the relative abundance of potentially pathogenic bacterial genera on magpies. CONCLUSIONS: Our findings highlight the role of social interactions in shaping the assembly of the avian skin bacterial communities during the nestling period, as exemplified in a brood parasite-host system.

Molecular subtypes explain lupus epigenomic heterogeneity unveiling new regulatory genetic risk variants.

The heterogeneity of systemic lupus erythematosus (SLE) can be explained by epigenetic alterations that disrupt transcriptional programs mediating environmental and genetic risk. This study evaluated the epigenetic contribution to SLE heterogeneity considering molecular and serological subtypes, genetics and transcriptional status, followed by drug target discovery. We performed a stratified epigenome-wide association studies of whole blood DNA methylation from 213 SLE patients and 221 controls. Methylation quantitative trait loci analyses, cytokine and transcription factor activity - epigenetic associations and methylation-expression correlations were conducted. New drug targets were searched for based on differentially methylated genes. In a stratified approach, a total of 974 differential methylation CpG sites with dependency on molecular subtypes and autoantibody profiles were found. Mediation analyses suggested that SLE-associated SNPs in the HLA region exert their risk through DNA methylation changes. Novel genetic variants regulating DNAm in disease or in specific molecular contexts were identified. The epigenetic landscapes showed strong association with transcription factor activity and cytokine levels, conditioned by the molecular context. Epigenetic signals were enriched in known and novel drug targets for SLE. This study reveals possible genetic drivers and consequences of epigenetic variability on SLE heterogeneity and disentangles the DNAm mediation role on SLE genetic risk and novel disease-specific meQTLs. Finally, novel targets for drug development were discovered.

Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

A Genome-Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome.

OBJECTIVE: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. METHODS: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases. RESULTS: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT1-STAT4 with a genome-wide level of significance; 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele near HLA-DRA is associated with overexpression of HLA-DRB6, HLA-DRB9, HLA-DQA2, and HLA-DQB2 in immune cells, vascular tissue, and nervous tissue. This association is independent of the association between PAPS and HLA-DRB1*1302. Functional analyses highlighted immune-related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren syndrome, suggesting co-localized causal variations close to STAT1-STAT4, TNPO3, and BLK. CONCLUSION: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.

Microbiota and the Volatile Profile of Avian Nests Associate with Each Other and with the Intensity of Parasitism.

Bacteria have been suggested as being partially responsible for avian-nest odours and, thus, volatiles from their metabolism could influence the intensity of selection pressures due to parasites detecting olfactory cues of their hosts. Here, we tested this hypothesis by exploring intra- and interspecific variability in microbial environments, volatile profiles, and intensity of ectoparasitism by Carnus hemapterus in nests of ten avian species. As expected, we found that (i) alpha and beta diversity of microbial and volatile profiles associated to each other. Moreover, (ii) alpha diversity of bacteria and volatiles of nest environment, as well as some particular bacteria and volatiles, associated with intensity of parasitism at early and late stage of the nestling period. Finally, (iii) alpha diversity of the nest microbiota, as well as some particular bacteria and volatiles, was correlated to fledging success. When considering them together, the results support the expected links between microbial environment and nest odours in different bird species, and between microbial environment and both ectoparasitism intensity and fledging success. Relative abundances of particular volatiles and bacteria predicted ectoparasitism and/or fledging success. Future research should prioritize experimental approaches directed to determine the role of bacteria and volatiles in the outcomes of host-ectoparasite interactions.

Volatiles of symbiotic bacterial origin explain ectoparasitism and fledging success of hoopoes.

BACKGROUND: Some parasites use olfactory cues to detect their hosts and, since bacterial symbionts are partially responsible for animal odours, they could influence host parasitism. By autoclaving nest materials of hoopoe (Upupa epops) nests before reproduction started, we explored the hypothetical links between host-associated bacteria, volatiles and parasitism. During the nestling stage, we (i) estimated the level of ectoparasitism by chewing lice (Suborder Mallophaga) in adult hoopoe females and by Carnus haemapterus flies in nestlings, and (ii) characterized microbial communities and volatile profiles of nest environments (nest material and nest cavity, respectively) and uropygial secretions. RESULTS: Experimental nests had less diverse bacterial communities and more diverse volatile profiles than control nests, while occupants experienced lower intensity of parasitism in experimental than in control nests. The experiment also affected beta diversity of the microbial communities of nest material and of the volatiles of the nestling uropygial secretions. Moreover, microbial communities of uropygial secretions and of nest materials covaried with their volatile profiles, while the volatile profile of the bird secretions explained nest volatile profile. Finally, a subset of the volatiles and bacteria detected in the nest material and uropygial secretions were associated with the ectoparasitism intensity of both adult females and nestlings, and with fledging success. CONCLUSIONS: These results show that a component of animal odours is linked with the microbial communities of the host and its reproductive environment, and emphasize that the associations between bacteria, ectoparasitism and reproductive success are partially mediated by volatiles of bacterial origin. Future work should focus on mechanisms underlying the detected patterns.

A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome.

Objectives: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS. Methods: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases. Results: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT4 with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele in the HLA class II locus is associated with overexpression of HLA-DRB6 , HLA-DRB9 , HLA-DPB2 , HLA-DQA2 and HLA-DQB2 , and is independent of the association between PAPS and HLA-DRB1*1302 . Functional analyses highlighted immune and nervous system related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren's syndrome, suggesting colocalized causal variations close to STAT4 , TNPO3 , and BLK . Conclusions: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.