Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term’s historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth.

The highly proliferating C2A subtype is characterized by topoisomerase 2-alpha gene up-regulation and FA pathway activation, and the HB therapeutic arsenal could include bortezomib for the treatment of patients with the most aggressive tumors. (Hepatology 2018;68:89-102).

T he unconventional splicing of Hac1 by the ribonuclease Ire1 is a key event in the activation of the unfolded protein response (UPR) in Saccharomyces cerevisiae. This splicing is independent of the spliceosome and is mediated by a secondary structure at the intron-exon boundaries of the mRNA. Similar unconventional splicing was also described for the gene Xbp1 in human, mouse, Caenorhabditis elegans and Drosophila melanogaster, and for Hac1 in five other fungi. We used reported RNA structures to build a multiple sequence alignment and the Infernal package to search for homologous structures. We identified homologous noncanonical intron structures in 128 out of 156 searched eukaryotic genomes. Our results show that the sequence of the Hac1/Xbp1 intron is highly conserved only around the splice sites recognized by Ire1. The consensus structure of the Hac1/Xbp1 mRNA is well conserved in Fungi and Metazoa and resembles structures previously described. We show that a typical Hac1/Xbp1 intron is very short, only 20-26 bases, whereas yeast species have a long intron (>100 bases). We identified six species with unambiguous Hac1/Xbp1 homologs that have lost the non-canonical intron structure. We propose that these species use a different mechanism to regulate the UPR.

MicroRNAs are essential post-transcriptional regulators. Many animal microRNAs are clustered in the genome, and it has been shown that clustered microRNAs may be transcribed as a single transcript. Polycistronic microRNAs are often members of the same family, suggesting a role of tandem duplication in the emergence of clusters. The mir-2 microRNA family is the largest in Drosophila melanogaster, with 8 members that are mostly clustered in the genome. Previous studies suggest that the copy number and genomic distribution of mir-2 family members has been subject to significant change during evolution. The effects of such changes on their function are still unknown. Here we study the evolution of function in the mir-2 family. Our analyses show that, in spite of the change in number and organization among invertebrates, most mir-2 loci produce very similar mature microRNA products. Multiple mature miR-2 sequences are predicted to target genes involved in neural development in Drosophila. These targeting properties are conserved in the distant species Caenorhabditis elegans. Duplication followed by functional diversification is frequent during protein-coding gene evolution. However, our results suggest that the production of microRNA clusters by gene duplication rarely involves functional changes. This pattern of functional redundancy among clustered paralogous microRNAs reflects birth-and-death evolutionary dynamics. However, we identified a small number of mir-2 sequences in Drosophila that may have undergone functional shifts associated with genomic rearrangements. Therefore, redundancy in microRNA families may facilitate the acquisition of novel functional features.

Introns in protein-coding genes are very rare in hemiascomycetous yeast genomes. It has been suggested that these species have experienced extensive intron loss during their evolution from the postulated intron-rich fungal ancestor. However, no intron-devoid yeast species have been identified and some of the introns remaining within the genomes of intron-poor species, such as Saccharomyces cerevisiae, appear to be beneficial during growth under stress conditions. In order to reveal the pattern of intron retention within intron-poor yeast species and better understand the mechanisms of intron evolution, we generated a comprehensive set of 250 orthologous introns in the 20 species that comprise the Saccharomycetaceae, by analyzing RNA deep-sequencing data and alignments of intron-containing genes. Analysis of these intron sets shows that intron loss is at least two orders of magnitude more frequent than intron gain. Fine mapping of intron positions shows that intron sliding is rare, and that introns are almost always removed without changing the primary sequence of the encoded protein. The latter finding is consistent with the prevailing view that homologous recombination between reverse-transcribed mature mRNAs and the corresponding genomic locus is the primary mechanism of intron loss. However, we also find evidence that loss of a small number of introns is mediated by micro-homology, and that the number of intron losses is diminished in yeast species that have lost the microhomology end joining and nonhomologous end joining machinery.

Microbiota-gut-brain (MGB) research is a fast-growing field of inquiry with important implications for how human brain function and behaviour are understood. Researchers manipulate gut microbes ('microbiota') to reveal connections between intestinal microbiota and normal brain functions (e.g., cognition, emotion, memory) or pathological states (e.g., anxiety and mood disorders, neural developmental disorders such as autism). Many claims are made about causal relationships between gut microbiota and human behaviour. By uncovering these relationships, MGB research aims to offer new explanations of mental health and potential avenues of treatment.So far, limited evaluation has been made of MGB's methods and its core experimental findings, many of which are extensively reiterated in copious reviews of the field. These factors, plus the self-help potential of MGB, have combined to encourage uncritical public uptake of MGB discoveries. Both social and professional media focus on the potential for dietary intervention in mental health, and causal relationships are assumed to be established.Our target article has two main aims. One is to examine critically the core practices and findings of experimental MGB research, and to raise questions about them for brain and behavioural scientists who may not be familiar with the field. The other is to challenge the way in which MGB findings are presented. Our positive goal is to suggest how current problems and weaknesses may be addressed, in order for both scientific and public audiences to gain a clearer picture of MGB research and its strengths and limitations.

Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut inflammation and microbiota dysbiosis is still poorly understood. The main objective of this study was to assess gut microbiota composition in CF children depending on their intestinal inflammation. We collected fecal samples from 20 children with CF. Fecal calprotectin levels were measured and fecal microbiota was analyzed by 16S rRNA sequencing. We observed intestinal inflammation was associated with microbiota disturbances characterized mainly by increased abundances of Staphylococcus, Streptococcus, and Veillonella dispar, along with decreased abundances of Bacteroides, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Those changes exhibited similarities with that of Crohn’s disease (CD), as evidenced by the elevated CD Microbial-Dysbiosis index that we applied for the first time in CF. Furthermore, the significant over-representation of Streptococcus in children with intestinal inflammation appears to be specific to CF and raises the issue of gut–lung axis involvement. Taken together, our results provide new arguments to link gut microbiota and intestinal inflammation in CF and suggest the key role of the gut–lung axis in the CF evolution.

Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment that can predict the clinical response as a biomarker, with a higher proportion of Burkholderiales order in future responder patients. This study suggests a cross-influence between anti-TNF-α treatment and intestinal microbiota. If its results are confirmed on larger groups of patients, it may pave the way to the development of predictive tests suitable for clinical practices.