scholarly journals Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett’s esophagus

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nandan P. Deshpande ◽  
Stephen M. Riordan ◽  
Claire J. Gorman ◽  
Shaun Nielsen ◽  
Tonia L. Russell ◽  
...  

Abstract Background The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host. Methods Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest. Results Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of Campylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between Campylobacter and napsin B aspartic peptidase. Targeted culture of Campylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these Campylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the Campylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression. Conclusions We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.

2020 ◽  
Author(s):  
Pieter De Maayer ◽  
Talia Pillay ◽  
Teresa A Coutinho

Abstract Background Flagellar motility is an efficient means of movement that allows bacteria to successfully colonize and compete with other microorganisms within their respective environments. The production and functioning of these structures is highly energy intensive and as such flagellar motility is a tightly regulated process. Despite this, some bacteria have been observed to possess multiple flagellar systems which allow distinct forms of motility. Results Comparative genomic analyses showed that, in addition to the previously identified primary peritrichous (flag-1) and secondary, lateral (flag-2) flagellar loci, three novel types of flagellar loci, varying in both gene content and gene order, are encoded on the genomes of members of the order Enterobacterales. The flag-3 and flag-4 loci encode peritrichous flagellar systems while the flag-5 locus encodes a polar flagellum. In total, 798/4,028 (~ 20%) of the studied taxa incorporate dual flagellar systems, while nineteen taxa incorporate three distinct flagellar loci. Phylogenetic analyses indicate the complex evolutionary histories of the flagellar systems among the Enterobacterales. Conclusions Supernumerary flagellar loci are relatively common features across a broad taxonomic spectrum in the order Enterobacterales. Here, we report for the first time on the occurrence of two peritrichous flagellar loci in some enterobacterial taxa, as well as the occurrence of three flagellar systems in select members of the Enterobacterales. Considering the energetic burden of maintaining and operating multiple flagellar systems, they are likely to play a role in the ecological success of members of this family and we postulate on their potential biological functions.


Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 95
Author(s):  
Yan Jia ◽  
Bo Yang ◽  
Paul Ross ◽  
Catherine Stanton ◽  
Hao Zhang ◽  
...  

The potential probiotic benefits of Lactobacillus mucosae have received increasing attention. To investigate the genetic diversity of L. mucosae, comparative genomic analyses of 93 strains isolated from different niches (human and animal gut, human vagina, etc.) and eight strains of published genomes were conducted. The results showed that the core genome of L. mucosae mainly encoded translation and transcription, amino acid biosynthesis, sugar metabolism, and defense function while the pan-genomic curve tended to be close. The genetic diversity of L. mucosae mainly reflected in carbohydrate metabolism and immune/competitive-related factors, such as exopolysaccharide (EPS), enterolysin A, and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas. It was worth noting that this research firstly predicted the complete EPS operon shared among L. mucosae. Additionally, the type IIIA CRISPR-Cas system was discovered in L. mucosae for the first time. This work provided new ideas for the study of this species.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3171
Author(s):  
Sandrine M. Caputo ◽  
Dominique Telly ◽  
Adrien Briaux ◽  
Julie Sesen ◽  
Maurizio Ceppi ◽  
...  

Background: Large genomic rearrangements (LGR) in BRCA1 consisting of deletions/duplications of one or several exons have been found throughout the gene with a large proportion occurring in the 5′ region from the promoter to exon 2. The aim of this study was to better characterize those LGR in French high-risk breast/ovarian cancer families. Methods: DNA from 20 families with one apparent duplication and nine deletions was analyzed with a dedicated comparative genomic hybridization (CGH) array, high-resolution BRCA1 Genomic Morse Codes analysis and Sanger sequencing. Results: The apparent duplication was in fact a tandem triplication of exons 1 and 2 and part of intron 2 of BRCA1, fully characterized here for the first time. We calculated a causality score with the multifactorial model from data obtained from six families, classifying this variant as benign. Among the nine deletions detected in this region, eight have never been identified. The breakpoints fell in six recurrent regions and could confirm some specific conformation of the chromatin. Conclusions: Taken together, our results firmly establish that the BRCA1 5′ region is a frequent site of different LGRs and highlight the importance of the segmental duplication and Alu sequences, particularly the very high homologous region, in the mechanism of a recombination event. This also confirmed that those events are not systematically deleterious.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Josué Barrera-Redondo ◽  
Guillermo Sánchez-de la Vega ◽  
Jonás A. Aguirre-Liguori ◽  
Gabriela Castellanos-Morales ◽  
Yocelyn T. Gutiérrez-Guerrero ◽  
...  

AbstractDespite their economic importance and well-characterized domestication syndrome, the genomic impact of domestication and the identification of variants underlying the domestication traits in Cucurbita species (pumpkins and squashes) is currently lacking. Cucurbita argyrosperma, also known as cushaw pumpkin or silver-seed gourd, is a Mexican crop consumed primarily for its seeds rather than fruit flesh. This makes it a good model to study Cucurbita domestication, as seeds were an essential component of early Mesoamerican diet and likely the first targets of human-guided selection in pumpkins and squashes. We obtained population-level data using tunable Genotype by Sequencing libraries for 192 individuals of the wild and domesticated subspecies of C. argyrosperma across Mexico. We also assembled the first high-quality wild Cucurbita genome. Comparative genomic analyses revealed several structural variants and presence/absence of genes related to domestication. Our results indicate a monophyletic origin of this domesticated crop in the lowlands of Jalisco. We found evidence of gene flow between the domesticated and wild subspecies, which likely alleviated the effects of the domestication bottleneck. We uncovered candidate domestication genes that are involved in the regulation of growth hormones, plant defense mechanisms, seed development, and germination. The presence of shared selected alleles with the closely related species Cucurbita moschata suggests domestication-related introgression between both taxa.


Gene ◽  
2021 ◽  
pp. 145715
Author(s):  
Ying Zhang ◽  
Zhengfeng Wang ◽  
Yanan Guo ◽  
Sheng Chen ◽  
Xianyi Xu ◽  
...  

2021 ◽  
Author(s):  
Yang Liu ◽  
Wei Xiao ◽  
Leilei Yu ◽  
Fengwei Tian ◽  
Gang Wang ◽  
...  

Irritable bowel syndrome (IBS) is a chronic intestinal disorder accompanied by low-grade inflammation, visceral hypersensitivity, and gut microbiota dysbiosis. Several studies have indicated that Lactobacillus supplementation can help to alleviate...


2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Chao Ye ◽  
Jiqiang Wu ◽  
Wu Tong ◽  
Tongling Shan ◽  
Xuefei Cheng ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simin Chai ◽  
Ran Tian ◽  
Juanjuan Bi ◽  
Shixia Xu ◽  
Guang Yang ◽  
...  

Abstract Background The mammalian testis is an important male exocrine gland and spermatozoa-producing organ that usually lies in extra-abdominal scrotums to provide a cooler environment for spermatogenesis and sperm storage. Testicles sometimes fail to descend, leading to cryptorchidism. However, certain groups of mammals possess inherently ascrotal testes (i.e. testes that do not descend completely or at all) that have the same physiological functions as completely descended scrotal testes. Although several anatomical and hormonal factors involved in testicular descent have been studied, there is still a paucity of comprehensive research on the genetic mechanisms underlying the evolution of testicular descent in mammals and how mammals with ascrotal testes maintain their reproductive health. Results We performed integrative phenotypic and comparative genomic analyses of 380 cryptorchidism-related genes and found that the mammalian ascrotal testes trait is derived from an ancestral scrotal state. Rapidly evolving genes in ascrotal mammals were enriched in the Hedgehog pathway—which regulates Leydig cell differentiation and testosterone secretion—and muscle development. Moreover, some cryptorchidism-related genes in ascrotal mammals had undergone positive selection and contained specific mutations and indels. Genes harboring convergent/parallel amino acid substitutions between ascrotal mammals were enriched in GTPase functions. Conclusions Our results suggest that the scrotal testis is an ancestral state in mammals, and the ascrotal phenotype was derived multiple times in independent lineages. In addition, the adaptive evolution of genes involved in testicular descent and the development of the gubernaculum contributed to the evolution of ascrotal testes. Accurate DNA replication, the proper segregation of genetic material, and appropriate autophagy are the potential mechanisms for maintaining physiological normality during spermatogenesis in ascrotal mammals. Furthermore, the molecular convergence of GTPases is probably a mechanism in the ascrotal testes of different mammals. This study provides novel insights into the evolution of the testis and scrotum in mammals and contributes to a better understanding of the pathogenesis of cryptorchidism in humans.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3162 ◽  
Author(s):  
Ana Gutiérrez-Preciado ◽  
Carlos Vargas-Chávez ◽  
Mariana Reyes-Prieto ◽  
Omar F. Ordoñez ◽  
Diego Santos-García ◽  
...  

We report the genome sequence ofExiguobacterium chiriqhuchastr. N139, isolated from a high-altitude Andean lake. Comparative genomic analyses of theExiguobacteriumgenomes available suggest that our strain belongs to the same species as the previously reportedE. pavilionensisstr. RW-2 andExiguobacteriumstr. GIC 31. We describe this species and propose thechiriqhuchaname to group them. ‘Chiri qhucha’ in Quechua means ‘cold lake’, which is a common origin of these three cosmopolitan Exiguobacteria. The 2,952,588-bpE. chiriqhuchastr. N139 genome contains one chromosome and three megaplasmids. The genome analysis of the Andean strain suggests the presence of enzymes that conferE. chiriqhuchastr. N139 the ability to grow under multiple environmental extreme conditions, including high concentrations of different metals, high ultraviolet B radiation, scavenging for phosphorous and coping with high salinity. Moreover, the regulation of its tryptophan biosynthesis suggests that novel pathways remain to be discovered, and that these pathways might be fundamental in the amino acid metabolism of the microbial community from Laguna Negra, Argentina.


2017 ◽  
Vol 5 (32) ◽  
Author(s):  
Rose Waldron ◽  
Jamie McGowan ◽  
Natasha Gordon ◽  
Charley McCarthy ◽  
E. Bruce Mitchell ◽  
...  

ABSTRACT Dermatophagoides pteronyssinus is the European dust mite and a major source of human allergens. Here, we present the first draft genome sequence of the mite, as well as the ab initio gene prediction and functional analyses that will facilitate comparative genomic analyses with other mite species.


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