Francesc Català-Moll

Identifying animal species that are susceptible to the plethora of existing and emerging viruses is critical for predicting and containing disease outbreaks. Current efforts to assess viral tropism largely rely on experimental infection models, but such experiments are logistically and ethically infeasible for many wildlife species. To tackle this challenge, we developed a panel of airway organoids from ten taxonomically diverse wildlife and livestock species and evaluated their susceptibility to influenza viruses of mammalian (pH1N1) and avian (H5N1) origin. Our analyses revealed large host-specific differences in infection rate and cytopathogenicity that aligned with known in vivo data and field observations. Furthermore, we demonstrated that this organoid panel can serve as a powerful tool to elucidate receptor-binding mechanisms, viral dynamics and early host adaptation in poorly characterized animal hosts. In summary, this work provides a robust and ethically viable approach for evaluating viral tropism and adaptation in wildlife species, and may aid current pandemic preparedness, zoonotic disease surveillance and wildlife conservation efforts.

Late presentation of HIV-1 infection is linked to gut dysbiosis, impaired immune reconstitution, excess inflammation, immune activation, and increased morbidity and mortality. It is unclear if antiretroviral therapy initiation can reverse HIV-associated gut dysbiosis at all, or if specific antiretroviral regimens are more effective in restoring the gut microbiota than others. This has important implications for the long-term health of individuals with HIV. In this multicenter, open-label, randomized clinical trial (NCT02337322), 88 antiretroviral-naïve individuals with advanced HIV-1 infection (median CD4+ T cells of 34 cells/mm³) were randomized (1:1) to initiate lamivudine/abacavir plus either dolutegravir or ritonavir-boosted darunavir, and were followed for 2 years. Both groups had similar HIV-1 suppression rates and recovery of CD4+ T cells. However, treatment with dolutegravir led to increased gut microbial richness and diversity and enrichment of specific microbial taxa and metabolic pathways. These changes were associated with reduced inflammation and lower immune activation, outcomes that did not occur with darunavir/ritonavir. After two years, participants on dolutegravir-based therapy had gut microbiota profiles more closely resembling those of people without HIV, compared to individuals taking darunavir/ritonavir. In summary, dolutegravir-based therapy restores the gut microbiota more effectively than darunavir/ritonavir in patients who present late with HIV.

Identifying animal species that are susceptible to the plethora of existing and emerging viruses is critical for predicting and containing disease outbreaks. Current efforts to assess viral tropism largely rely on experimental infection models, but such experiments are logistically and ethically infeasible for many wildlife species. To tackle this challenge, we developed a panel of airway organoids from ten taxonomically diverse wildlife and livestock species and evaluated their susceptibility to influenza viruses of mammalian (pH1N1) and avian (H5N1) origin. Our analyses revealed large species-specific differences in infection rate and cytopathogenicity that aligned with known in vivo data and field observations. Furthermore, we demonstrated that this organoid panel can serve as a powerful tool to elucidate receptor-binding mechanisms, viral dynamics, and early host adaptation in poorly characterized animal species. In summary, this work provides a robust and ethically viable approach for evaluating viral tropism and adaptation in wildlife species, and fills a critical gap in current pandemic preparedness, zoonotic disease surveillance, and wildlife conservation efforts.

Late HIV-1 presentation is linked to impaired immune reconstitution, excess inflammation, immune activation, and increased morbidity and mortality. It also leads to gut dysbiosis, which is believed to worsen all such conditions. It is not clear if antiretroviral therapy initiation can reverse HIV-associated gut dysbiosis at all, or if specific antiretroviral regimens with higher intestinal penetration are more effective in restoring the gut microbiota than others, which has important implications for the long-term health of individuals with HIV. In this multicenter, open-label, randomized clinical trial (NCT02337322), 88 antiretroviral-naïve individuals with advanced HIV-1 infection (median CD4+ 34 cells/mm3) were randomized (1:1) to initiate lamivudine/abacavir plus either dolutegravir or ritonavir-boosted darunavir, and were followed for 2 years. Both groups achieved similar HIV-1 suppression and CD4+ count recovery. However, subjects starting dolutegravir experienced increases in gut microbial diversity and enrichment of beneficial commensal taxa and functional microbial pathways, which correlated with reductions in systemic inflammation and immune activation. These changes were not observed with darunavir/ritonavir treatment. In conclusion, treatment regimens that include dolutegravir are more likely to restore at 2 years the architecture and function of the gut microbiota in individuals with advanced HIV compared to those that include darunavir/ritonavir and should therefore be prioritized.

Although SARS-CoV-2 reinfections remain a concern for healthcare systems worldwide, the factors driving them are still not fully understood. In this study, we examined data for 3303 individuals who experienced two SARS-CoV-2 infections between March 2020 and May 2022 from both clinical and viral genomics perspectives. Our findings indicate that viral evolution was the primary driver of reinfection. However, chronic conditions were common among reinfected individuals, including those under 26 years old, suggesting that the presence of underlying and/or chronic conditions increases susceptibility to reinfection. The median time elapsed between infections was one year, often coinciding with the emergence of new variants. While vaccination showed only a limited protective effect against reinfection, it drastically decreased the hospitalization rate, underscoring its role in mitigating disease severity. Our findings point to the need for more flexible vaccination strategies, especially for individuals with chronic conditions. Understanding the interactions between host factors and viral evolution is critical to strengthening prevention strategies and reducing the burden of reinfections and their possible long-term complications.

Summary: The dar R package streamlines differential abundance (DA) testing in microbiome research by integrating state-of-the-art DA methods—such as DESeq2, ALDEx2, ANCOM-BC, and MetagenomeSeq—within a customizable consensus-based framework, thereby enhancing the robustness and reproducibility of DA results. Leveraging microbiome data in phyloseq or TreeSummarizedExperiment formats, dar organizes analysis steps in a modular recipe object, enabling users to easily incorporate preprocessing tasks such as taxonomic filtering, rarefaction, and subsetting, alongside multiple DA analysis methods. Dedicated visualization tools facilitate the definition of a consensus by illustrating the overlap among methods, empowering users to refine analysis strategies and display final results. Reproducibility is supported through functions that export and import entire analysis workflows, making dar a comprehensive solution for addressing the complex, high-dimensional nature of microbiome data. Availability and implementation: dar is an R package available from Bioconductor ≥ 3.19 ( https://www.bioconductor.org/packages/dar ) for R ≥ 4.4. The software is distributed under the MIT License and includes example datasets. Contact: fcatala@irsicaixa.es Supplementary information: Additional documentation is available at https://microbialgenomics-irsicaixaorg.github.io/dar

Purpose of review: Condomless receptive anal intercourse stands out as the sexual practice with highest risk of HIV-1 infection. Recent studies have suggested that the gut microbiome influences susceptibility to HIV transmission. This review explores recent research on host risk factors, the rectal microbiome composition, local inflammation, and bacteria-derived mediators that may affect HIV transmission. Recent findings: Constitutive host factors such as rectal mucosal structure and immune cell populations in the rectum contribute to increased susceptibility. Changes in the composition of the rectal microbiota, influenced by sexual practices and HIV infection modulate immune activation and inflammation, impacting HIV susceptibility. Bacteria-derived mediators may further influence immune responses and HIV replication in the rectal mucosa. Summary: Understanding the role of the rectal microbiome in HIV transmission has important clinical implications. Targeted interventions that modulate the microbiome may reduce susceptibility to HIV transmission by regulating immune responses and inflammation. Further research into the host–microbiome interactions could lead to novel preventive and therapeutic strategies to mitigate HIV transmission.