Gut virome in inflammatory bowel disease and beyond.

OBJECTIVE: The gut virome is a dense community of viruses inhabiting the gastrointestinal tract and an integral part of the microbiota. The virome coexists with the other components of the microbiota and with the host in a dynamic equilibrium, serving as a key contributor to the maintenance of intestinal homeostasis and functions. However, this equilibrium can be interrupted in certain pathological states, including inflammatory bowel disease, causing dysbiosis that may participate in disease pathogenesis. Nevertheless, whether virome dysbiosis is a causal or bystander event requires further clarification. DESIGN: This review seeks to summarise the latest advancements in the study of the gut virome, highlighting its cross-talk with the mucosal microenvironment. It explores how cutting-edge technologies may build upon current knowledge to advance research in this field. An overview of virome transplantation in diseased gastrointestinal tracts is provided along with insights into the development of innovative virome-based therapeutics to improve clinical management. RESULTS: Gut virome dysbiosis, primarily driven by the expansion of Caudovirales, has been shown to impact intestinal immunity and barrier functions, influencing overall intestinal homeostasis. Although emerging innovative technologies still need further implementation, they display the unprecedented potential to better characterise virome composition and delineate its role in intestinal diseases. CONCLUSIONS: The field of gut virome is progressively expanding, thanks to the advancements of sequencing technologies and bioinformatic pipelines. These have contributed to a better understanding of how virome dysbiosis is linked to intestinal disease pathogenesis and how the modulation of virome composition may help the clinical intervention to ameliorate gut disease management.

Multi-cohort analysis of depression-associated gut bacteria sheds insight on bacterial biomarkers across populations.

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of gut bacteria in the diagnostics and treatment of depression. To minimise heterogenicity in data analysis, the present meta-analysis adopted a standardised bioinformatics and statistical pipeline to analyse 16S rRNA sequences of 1827 samples from eight different cohorts. Although changes in the overall bacterial community were identified by our meta-analysis, depressive-correlated changes in alpha-diversity were absent. Enrichment of Bacteroidetes, Parabacteroides, Barnesiella, Bacteroides, and Bacteroides vulgatus, along with depletion in Firmicutes, Dialister, Oscillospiraceae UCG 003 and UCG 002, and Bacteroides plebeius, were observed in depressive-associated bacteria. By contrast, elevated L-glutamine degradation, and reduced L-glutamate and L-isoleucine biosynthesis were identified in depressive-associated microbiomes. After systemically reviewing the data of these collected cohorts, we have established a bacterial classifier to identify depressive symptoms with AUC 0.834 and 0.685 in the training and external validation dataset, respectively. Moreover, a low-risk bacterial cluster for depressive symptoms was identified, which was represented by a lower abundance of Escherichia-Shigella, and a higher abundance of Faecalibacterium, Oscillospiraceae UCG 002, Ruminococcus, and Christensenellaceae R.7 group.

Role of gut microbiota in travel-related acquisition of extended spectrum ß-lactamase-producing Enterobacteriaceae.

BACKGROUND: International travel could facilitate the spread of antimicrobial-resistant bacteria including extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). Previous studies, which attempted to understand the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels, are limited to western travellers. METHODS: We established a prospective cohort of 90 Hong Kong travellers to investigate gut microbiota determinants and associated risk factors for the acquisition of ESBL-E. Baseline characteristics and travel-associated risk factors were gathered through questionnaires. Faecal samples were collected in 3-4 days before and after travel. Antimicrobial susceptibility of ESBL-E isolates was tested, and gut microbiota were profiled by 16S rDNA amplicon sequencing. Non-parametric tests were used to detect potential associations, and logistic regression models were used to quantify the associations. Random forest models were constructed to identify microbial predictors for ESBL-E acquisition. RESULTS: In total, 49 (54.4%) participants were tested negative for ESBL-E colonization before travel and were followed up after travel. A total of 60 ESBL-E isolates were cultured from 20 (40.8%) participants. Having low Actinobacteria richness and low abundance of short-chain fatty acid-producing bacteria in the gut microbiota before travel increased the risk of acquiring ESBL-E and the risk can be further exacerbated by eating raw seafood during travel. Besides, post-travel ESBL-E positive participants had increased abundances of several opportunistic pathogens such as Staphylococcus, Enterococcus, Escherichia/Shigella and Klebsiella. The random forest model integrating pre-travel microbiota and the identified travel-related risk factor could predict ESBL-E acquisition with an area under the curve of 75.4% (95% confidence interval: 57.9-93.0%). CONCLUSIONS: In this study, we identified both travel-related risk factors and microbiota predictors for the risk of ESBL-E acquisition. Our results provide foundational knowledge for future developments of microbiota-based interventions to prevent ESBL-E acquisition during international travels.