Wenchao Wei, Chi Chun Wong, Zhongjun Jia, Weixin Liu, Changan Liu, Fenfen Ji, Yasi Pan, Feixue Wang, Guoping Wang, Liuyang Zhao, Eagle S H Chu, Xiang Zhang, Joseph J Y Sung, Jun Yu <<<

Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by C-inulin. Integration of C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease. <<<

Aspergillus fumigatus is an environmental saprobe and opportunistic human fungal pathogen. Despite an estimated annual occurrence of more than 300,000 cases of invasive disease worldwide, a comprehensive survey of the genomic diversity present in A. fumigatus-including the relationship between clinical and environmental isolates and how this genetic diversity contributes to virulence and antifungal drug resistance-has been lacking. In this study we define the pan-genome of A. fumigatus using a collection of 300 globally sampled genomes (83 clinical and 217 environmental isolates). We found that 7,563 of the 10,907 unique orthogroups (69%) are core and present in all isolates and the remaining 3,344 show presence/absence of variation, representing 16-22% of the genome of each isolate. Using this large genomic dataset of environmental and clinical samples, we found an enrichment for clinical isolates in a genetic cluster whose genomes also contain more accessory genes, including genes coding for transmembrane transporters and proteins with iron-binding activity, and genes involved in both carbohydrate and amino-acid metabolism. Finally, we leverage the power of genome-wide association studies to identify genomic variation associated with clinical isolates and triazole resistance as well as characterize genetic variation in known virulence factors. This characterization of the genomic diversity of A. fumigatus allows us to move away from a single reference genome that does not necessarily represent the species as a whole and better understand its pathogenic versatility, ultimately leading to better management of these infections. <<<