Microbial and metabolic multi-omic correlations in systemic sclerosis patients

Intestinal microbiota has been associated with systemic autoimmune diseases, yet the functional consequences of these associations are elusive. We characterized the fecal microbiota (16S rRNA gene amplification and sequencing) and the plasma metabolome (high-performance liquid chromatography coupled to mass spectrometry) in 59 patients with systemic sclerosis (SSc) and 28 healthy controls (HCs). Microbial and metabolic data were cross-correlated to find meaningful associations after extensive data mining analysis and internal validation. Our data show that a reduced model of nine bacteria is capable of differentiating HCs from SSc patients. SSc gut microbiota is characterized by a reduction in protective butyrate-producing bacteria and by an increase in proinflammatory noxious genera, especially Desulfovibrio. From the metabolic point of view, a multivariate model with 17 metabolite intermediates well distinguished cases from controls. The most interesting peaks we found were identified as glycerophospholipid metabolites and benzene derivatives. The microbial and metabolic data showed significant interactions between Desulfovibrio and alpha-N-phenylacetyl-L-glutamine and 2,4-dinitrobenzenesulfonic acid. Our data suggest that in SSc, intestinal microbiota is characterized by proinflammatory alterations subtly entwined with the metabolic state. Desulfovibrio is a relevant actor in gut dysbiosis that may promote intestinal damage and influence amino acid metabolism.