The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.

Group A rotavirus classification is currently based on the molecular properties of the two outer layer proteins, VP7 and VP4, and the middle layer protein, VP6. As reassortment of all the 11 rotavirus gene segments plays a key role in generating rotavirus diversity in nature, a classification system that is based on all the rotavirus gene segments is desirable for determining which genes influence rotavirus host range restriction, replication, and virulence, as well as for studying rotavirus epidemiology and evolution. Toward establishing such a classification system, gene sequences encoding VP1 to VP3, VP6, and NSP1 to NSP5 were determined for human and animal rotavirus strains belonging to different G and P genotypes in addition to those available in databases, and they were used to define phylogenetic relationships among all rotavirus genes. Based on these phylogenetic analyses, appropriate identity cutoff values were determined for each gene. For the VP4 gene, a nucleotide identity cutoff value of 80% completely correlated with the 27 established P genotypes. For the VP7 gene, a nucleotide identity cutoff value of 80% largely coincided with the established G genotypes but identified four additional distinct genotypes comprised of murine or avian rotavirus strains. Phylogenetic analyses of the VP1 to VP3, VP6, and NSP1 to NSP5 genes showed the existence of 4, 5, 6, 11, 14, 5, 7, 11, and 6 genotypes, respectively, based on nucleotide identity cutoff values of 83%, 84%, 81%, 85%, 79%, 85%, 85%, 85%, and 91%, respectively. In accordance with these data, a revised nomenclature of rotavirus strains is proposed. The novel classification system allows the identification of (i) distinct genotypes, which probably followed separate evolutionary paths; (ii) interspecies transmissions and a plethora of reassortment events; and (iii) certain gene constellations that revealed (a) a common origin between human Wa-like rotavirus strains and porcine rotavirus strains and (b) a common origin between human DS-1-like rotavirus strains and bovine rotaviruses. These close evolutionary links between human and animal rotaviruses emphasize the need for close simultaneous monitoring of rotaviruses in animals and humans.Group A rotaviruses are major pathogens associated with acute gastroenteritis in humans and animals. Rotaviruses form a genus in the Reoviridae family and are characterized by a segmented double-stranded RNA genome (3, 16). The rotavirus genome is enclosed in a triple-layered icosahedral capsid and consists of 11 segments, encoding six viral structural proteins (VP1 to VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6) (16). Each genome segment, with the exception of gene 11 that encodes two proteins (NSP5 and NSP6), codes for a single viral protein. The inner layer of the rotavirus virion is mainly composed of VP2, which encases VP1, the viral RNA-dependent RNA polymerase, and VP3, the viral capping enzyme (16). The middle layer of the virion is composed entirely of VP6 trimers, which determine rotavirus ...

Immune-checkpoint blockade (ICB) combined with neoadjuvant chemotherapy improves pathological complete response in breast cancer (BC). To understand why only a subset of tumors respond to ICB, patients with hormone receptor-positive or triple-negative BC were treated with anti-PD1 prior to surgery. Paired pre-versus on-treatment biopsies from treatment-naïve patients receiving anti-PD-1 (n=29) or patients receiving neoadjuvant chemotherapy prior to anti-PD1 (n=11) were subjected to single-cell transcriptome, T-cell receptor and proteome profiling. One-third of tumors contained PD1-expressing T-cells, which clonally expanded upon anti-PD1 treatment irrespective of tumor subtype. Expansion mainly involved CD8 + T-cells with pronounced expression of cytotoxic-activity (PRF1, GZMB), immune-cell homing (CXCL13) and exhaustion markers (HAVCR2, LAG3), and CD4 + T-cells characterized by expression of T-helper-1 (IFNG) and follicular-helper (BCL6, CXCR5) markers. In pre-treatment biopsies, the relative frequency of immunoregulatory dendritic cells (PD-L1), specific macrophage phenotypes (CCR2 or MMP9) and cancer cells exhibiting MHC class I/II expression correlated positively with T-cell expansion. Conversely, undifferentiated preeffector/memory T-cells (TCF7, GZMK) or inhibitory macrophages (CXCR3, C3) were inversely correlated. Collectively, our data identify various immunophenotypes and associated gene sets that are positively or negatively correlated with T-cell expansion following anti-PD1. We shed light on the heterogeneity in treatment response to anti-PD1 in breast cancer.