During the 2008-2012 pertussis epidemic in Australia, pertactin (Prn)-negative Bordetella pertussis emerged. We analyzed 78 isolates from the 2013-2017 epidemic and documented continued expansion of Prn-negative ptxP3 B. pertussis strains. We also detected a filamentous hemagglutinin-negative and Prn-negative B. pertussis isolate.

Objective Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection. Design Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics Results Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics. Conclusion Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host. Trial registration number ACTRN12619000611123.

Macroautophagy/autophagy, a fundamental cell process for nutrient recycling and defense against pathogens (termed xenophagy), is crucial to human health. ATG16L2 (autophagy related 16 like 2) is an autophagic protein and a paralog of ATG16L1. Both proteins are implicated in similar diseases such as cancer and other chronic diseases; however, most autophagy studies to date have primarily focused on the function of ATG16L1, with ATG16L2 remaining uncharacterized and understudied. Overexpression of ATG16L2 has been reported in various cancers including colorectal, gastric, and prostate carcinomas, whereas altered methylation of ATG16L2 has been associated with lung cancer formation and poorer response to therapy in leukemia. In addition, ATG16L2 polymorphisms have been implicated in a range of other diseases including inflammatory bowel diseases and neurodegenerative disorders. Despite this likely role in human health, the function of this enigmatic protein in autophagy remains unknown. Here, we review current studies on ATG16L2 and collate evidence that suggests that this protein is a potential modulator of autophagy as well as the implications this has on pathogenesis. Abbreviations: ATG5: autophagy related 5; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; ATG16L2: autophagy related 16 like 2; CD: Crohn disease; IBD: inflammatory bowel diseases; IRGM: immunity related GTPase M; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PE: phosphatidylethanolamine; RB1CC1: RB1 inducible coiled-coil 1; SLE: systemic lupus erythematosus; WIPI2B: WD repeat domain, phosphoinositide interacting 2B

Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.