Project description:Members of the genus Hepacivirus have a broad range of hosts, with at least 14 species identified. To date, a highly pathogenic hepacivirus causing severe disease in animals has not been found. Here, by using high-throughput sequencing, a new hepacivirus was identified as the dominant and highly pathogenic virus in severe acute hepatitis outbreaks in bamboo rats (Rhizomys pruinosus), with ≈80% mortality; this virus emerged in February 2020 in two bamboo rat farms in China. Hepaciviral genome copies in bamboo rat liver were significantly higher than in other organs. Genomic sequences of hepacivirus strains from 12 sick bamboo rats were found to share 85.3 to 100% nucleotide (nt) identity and 94.9 to 100% amino acid (aa) identity and to share 79.7 to 87.8% nt and 90.4 to 97.8% aa identities with previously reported bamboo rat hepaciviruses of Vietnam and China. Sequence analysis further revealed the simultaneous circulation of genetically divergent hepacivirus variants within the two outbreaks. Phylogenetic analysis showed that hepacivirus strains from the present and previous studies formed an independent clade comprised of at least two genotypes, clearly different from all other known species, suggesting a novel species within the genus Hepacivirus. This is the first report of a non-human-infecting hepacivirus causing potentially fatal infection of bamboo rats, and the associated hepatitis in the animals potentially can be used to develop a surrogate model for the study of hepatitis C virus infection in humans and for the development of therapeutic strategies. IMPORTANCE Members of the genus Hepacivirus have a broad host range, with at least 14 species identified, but none is highly pathogenic to its host except for hepatitis C virus, which causes severe liver diseases in humans. In this study, a new liver-tropic hepacivirus species was identified by high-throughput sequencing as the pathogen associated with two outbreaks of severely acute hepatitis in hoary bamboo rats (Rhizomys pruinosus) on two farms in Hainan Province, China; this is the first reported highly pathogenic animal hepacivirus to our knowledge. Further phylogenetic analysis suggested that the hepaciviruses derived from hoary bamboo rats in either the current or previous studies represent a novel species within the genus Hepacivirus. This finding is a breakthrough that has significantly updated our understanding about the pathogenicity of animal hepaciviruses, and the hepacivirus-associated hepatitis in bamboo rats may have a use as an animal infection model to understand HCV infection and develop therapeutic strategies.
Project description:<p>Bamboo rats (<em>Rhizomys pruinosus</em>) are among the few mammals that lives on a bamboo-based diet which is mainly composed of lignocellulose. However, the mechanisms of adaptation of their gut microbiome and metabolic systems in the degradation of lignocellulose are largely unknown. Here, we conducted a multi-omics analysis on bamboo rats to investigate the interaction between their gut microbiomes and metabolic systems in the pre- and post-weaning periods, and observed significant relationships between dietary types, gut microbiome, serum metabolome and host gene expression. For comparison, published gut microbial data from the famous bamboo-eating giant panda (<em>Ailuropoda melanoleuca</em>) were also used for analysis. We found that the adaptation of the gut microbiome of the bamboo rat to a lignocellulose diet is related to a member switch in the order Bacteroidales from family <em>Bacteroidaceae</em> to family <em>Muribaculaceae</em>, while for the famous bamboo-eating giant panda, several aerobes and facultative anaerobes increase after weaning. The conversion of bacteria with an increased relative abundance in bamboo rats after weaning enriched diverse carbohydrate-active enzymes (CAZymes) associated with lignocellulose degradation and functionally enhanced the biosynthesis of amino acids and B vitamins. Meanwhile, the circulating concentration of short chain fatty acids (SCFAs) derived metabolites and the metabolic capacity of linoleic acid in the host were significantly elevated. Our findings suggest that fatty acid metabolism, including linoleic acid and SCFAs, are the main energy sources for bamboo rats in response to the low-nutrient</p>
Project description:Giant panda are carnivorous bears which feed almost exclusively on plant biomass (i.e. bamboo). The potential contribution of its gut microbiome to lignocellulose degradation has been mostly investigated with cultivation-independent approaches. Recently, we reported on the first lab-scale cultivation of giant panda gut microbiomes and described their actual fermentation capacity. Fermentation of bamboo leaf using green dung resulted in a neutral pH, the main products being ethanol, lactate and H2. Fermentation of bamboo pith using yellow dung resulted in an acidic pH, the main product being lactate. Here, we cultivated giant panda gut microbiomes to test 1) the impact of mixed dung as inoculum; 2) the fermentation capacity of solid lignocellulose as opposed to organics-rich biofluids in the dung; 3) the artificial shift of pH from neutral to acidic on bamboo leaf fermentation. Our results indicate that i) gut microbiomes fermentation of solid lignocellulose contributes up to a maximum of 1/3 even in the presence of organics-rich biofluids; ii) alcohols are an important product of bamboo leaf fermentation at neutral pH; iii) aside hemicellulose, gut microbiomes may degrade plant cell membranes to produce glycerol; iv) pH, rather than portion of bamboo, ultimately determines fermentation profiles and gut microbiome assemblage.
Project description:The iconic giant panda is an endangered species known worldwide for its peculiar dietary habits. While retaining the digestive system of a carnivore, the giant panda successfully moved into a diet almost exclusively based on bamboo. Digestion of lignocellulose is believed to be conducted solely by its gut microbiome, provided that no lignocellulose-degrading enzyme was found in the giant panda’s genome. Many reports focused on which lignocellulose component feeds the giant panda, while little effort was made to link the products of bamboo fermentation to the panda’s dietary choices. In the present study, fermentation of either green leaves or yellow pith was conducted in the laboratory using gut microbiomes derived from either green or yellow stools, respectively. Green leaves were fermented to ethanol, lactate and acetate, while yellow pith to lactate resembling, respectively, hetero/homo-fermentation patterns. Several microbial pathways (assessed by metaproteomics) related to hemicellulose rather than cellulose degradation. However, alpha-amylases (E.C. 3.2.1.1) from the giant panda itself were the most predominant enzyme (up to 60% of all metaproteins), indicating that they have a primary role in bamboo digestion. The distinct fermentation profiles resulting from digestion of selected portions of bamboo may be part of the feeding strategy of giant pandas.