16s RNA-based metagenomics reveal previously unreported gut microbiota associated with reactive arthritis and undifferentiated peripheral spondyloarthritis.

OBJECTIVES: Reactive arthritis (ReA) provides a unique opportunity to comprehend how a mucosal infection leads to inflammatory arthritis at a distant site without the apparent invasion of the pathogen. Unfortunately, conventional stool cultures after ReA provide limited information, and there is a dearth of metagenomic studies in ReA. The objective of this study was to identify gut microbiota associated with the development of ReA. METHODS: Patients with ReA or undifferentiated peripheral spondyloarthritis (UpSpA) were included if they presented within 4 weeks of the onset of the current episode of arthritis. Metagenomic DNA was extracted from the stools of these patients and of 36 age- and sex-similar controls. Sequencing and analysis were done using a standard 16S ribosomal pipeline. RESULTS: Of 55 patients, there was no difference between the gut microbiota of postdiarrheal ReA(n = 20) and of upSpA (n = 35). Comparing the gut microbiota of patients vs healthy controls, the patients had significantly higher alpha and beta diversity measures. After stringency filters, Proteobacteria had high abundance while Firmicutes had lesser as compared with the controls. Six families were overexpressed in patients, while another five were overexpressed in controls. Sixteen genera and 18 species were significantly different between patients and controls. At the species level there was strong association of Staphylococcus aureus, Clostridium septicum Klebsiella pneumoniae, Escherichia coli, Empedobacter brevis, Roseburia hominis, Bacillus velezensis, and Crassaminicella with ReA. CONCLUSION: The microbiota of classical gut-associated ReA and upSpA is similar. Patients have higher diversities in their gut microbiota compared with healthy controls. Both known and previously unreported species associated with ReA/upSpA were identified.

Impact of vaccination on SARS-CoV-2 evolution and immune escape variants.

Vaccines and host genetic factors can influence the SARS-CoV-2 evolution and emergence of new variants. Even vaccinated cases get affected as virus continues to evolve, raising concerns about vaccine efficacy and the emergence of immune escape variants. Here, we have analyzed 2295 whole-genome sequences of SARS-CoV-2 collected from vaccinated and unvaccinated cases to evaluate the impact of vaccines on virus diversity within hosts. Our comparative analysis revealed a significant higher incidence of intra-host single nucleotides variants (iSNVs) in vaccinated cases compared to unvaccinated ones (p value<0.0001). Furthermore, we have found that specific mutational processes, including APOBEC (C > T) mediated and ADAR1 (A > G) mediated mutations, were found more prevalent in vaccinated cases. Vaccinated cases exhibited higher accumulation of nonsynonymous mutation than unvaccinated cases. Fixed iSNVs were predominantly located in the ORF1ab and spike genes, several key omicron defining immune escape variants S477N, Q493R, Q498R, Y505H, L452R, and N501Y were identified in the RBD domain of spike gene in vaccinated cases. Our findings suggest that vaccine plays an important role in the evolution of the virus genome. The virus genome acquires random mutations due to error-prone replication of the virus, host modification through APOBEC and ADAR1 mediated editing mechanism, and oxidative stress. These mutations become fixed in the viral population due to the selective pressure imposed by vaccination.