Bellocchi, ChiaraFernández-Ochoa, ÁlvaroMontanelli, GaiaVigone, BarbaraSantaniello, AlessandroQuirantes-Piné, RosaBorrás-Linares, IsabelGerosa, MariaArtusi, CarolinaGualtierotti, RobertaSegura-Carrettero, AntonioAlarcón-Riquelme, Marta EBeretta, Lorenzo2023-01-252023-01-252019-08-232077-0383http://hdl.handle.net/10668/14445Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren's syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Sjögren’s syndromemetabolomicsmicrobiomicprimary anti-phosholipid syndromesystemic autoimmune diseasessystemic lupus erythematosusundifferentiated connective tissue diseasesresearch article31450824open access10.3390/jcm8091291PMC6780636https://www.mdpi.com/2077-0383/8/9/1291/pdf?version=1567074415https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780636/pdf