Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

Abstract

Dysbiosis 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.

The microbiome in rheumatology: Where are we and where should we go?

“…One of the earliest investigations showed decreased gut bacterial diversity and a lower Firmicutes:Bacteroidetes ratio in patients with SLE. 41 Other relatively small studies have also demonstrated gut bacterial dysbiosis in SLE, [42][43][44][45][46][47][48] mostly corroborating previous findings. Intriguingly, similar to RA, translocation of intestinal pathobionts was likewise noted with the description of Enterococcus gallinarum in liver biopsies of patients with SLE.…”

The Evolving Role of Gut Microbiota in the Management of Irritable Bowel Syndrome: An Overview of the Current Knowledge

“…However, most of them remain uncharacterized. Since this number is approximately equal to 10 times the total number of body cells, the interest in microbiota study for intestinal and extra-intestinal diseases is not surprising [18][19][20][21][22]. Advances in molecular biology techniques have significantly contributed to microbiome research.…”

Does the Microbiota Play a Pivotal Role in the Pathogenesis of Irritable Bowel Syndrome?

“…Today, it is known that although 98% of the gut microbiota is composed of four phyla of bacteria (Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria), the majority are either Firmicutes or Bacteroidetes [4,5]. With this premise, in the last decade, the gut microbiota has become a key topic in the investigation of several gastrointestinal (GI) as well as extra-GI diseases [6,7,8,9].…”