Correction: Longitudinal microbiome profiling reveals impermanence of probiotic bacteria in domestic pigeons.

[This corrects the article DOI: 10.1371/journal.pone.0217804.]

Longitudinal microbiome profiling reveals impermanence of probiotic bacteria in domestic pigeons.

Probiotics are bacterial species or assemblages that are applied to animals and plants with the intention of altering the microbiome in a beneficial way. Probiotics have been linked to positive health effects such as faster disease recovery times in humans and increased weight gain in poultry. Pigeon fanciers often feed their show pigeons probiotics with the intention of increasing flight performance. The objective of our study was to determine the effect of two different probiotics, alone and in combination, on the fecal microbiome of Birmingham Roller pigeons. We sequenced fecal samples from 20 pigeons divided into three probiotic treatments, including prior to, during, and after treatment. Pre-treatment and control group samples were dominated by Actinobacteria, Firmicutes, Proteobacteria, and Cyanobacteria. Administration of a probiotic pellet containing Enterococcus faecium and Lactobacillus acidophilus resulted in increase in average relative abundance of Lactobacillus spp. from 4.7 ± 2.0% to 93.0 ± 5.3%. No significant effects of Enterococcus spp. were detected. Probiotic-induced shifts in the microbiome composition were temporary and disappeared within 2 days of probiotic cessation. Administration of a probiotic powder in drinking water that contained Enterococcus faecium and three Lactobacillus species had minimal effect on the microbiome. We conclude that supplementing Birmingham roller pigeons with the probiotic pellets, but not the probiotic powder, temporarily changed the microbiome composition. A next step is to experimentally test the effect of these changes in microbiome composition on host health and physical performance

Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis

Common diseases such as endometriosis (ED), Alzheimer's disease (AD) and multiple sclerosis (MS) account for a significant proportion of the health care burden in many countries. Genome-wide association studies (GWASs) for these diseases have identified a number of individual genetic variants contributing to the risk of those diseases. However, the effect size for most variants is small and collectively the known variants explain only a small proportion of the estimated heritability. We used a linear mixed model to fit all single nucleotide polymorphisms (SNPs) simultaneously, and estimated genetic variances on the liability scale using SNPs from GWASs in unrelated individuals for these three diseases. For each of the three diseases, case and control samples were not all genotyped in the same laboratory. We demonstrate that a careful analysis can obtain robust estimates, but also that insufficient quality control (QC) of SNPs can lead to spurious results and that too stringent QC is likely to remove real genetic signals. Our estimates show that common SNPs on commercially available genotyping chips capture significant variation contributing to liability for all three diseases. The estimated proportion of total variation tagged by all SNPs was 0.26 (SE 0.04) for ED, 0.24 (SE 0.03) for AD and 0.30 (SE 0.03) for MS. Further, we partitioned the genetic variance explained into five categories by a minor allele frequency (MAF), by chromosomes and gene annotation. We provide strong evidence that a substantial proportion of variation in liability is explained by common SNPs, and thereby give insights into the genetic architecture of the diseases.10 page(s

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old