Systemic Sclerosis Linked With Altered Gut Microbiome

July 24, 2017

Low Bacteroidetes levels may suggest higher disease activity as in Crohn and other inflammatory diseases.

The numbers of Bacteroidetes bacteria in the GI tracts of 2 separate cohorts of patients with systemic sclerosis were significantly reduced when compared with healthy controls.

American patients with systemic sclerosis had more extensive alterations in their intestinal microbiota than those in a Norwegian cohort.

An abundance of Prevotella species was associated with moderate-to-severe GI symptoms in patients with systemic sclerosis. Clostridium species abundance was associated with low GI symptom severity, and Lactobacillus with none-to-mild constipation.

GI symptoms are common in systemic sclerosis, affecting up to 90% of patients. But Elizabeth Volkmann and fellow researchers at UCLA pointed out that very little is known about the pathogenesis of GI dysfunction in patients who have the disease.

GI dysfunction decreases quality of life and is difficult to treat, owing to a lack of understanding of its pathogenesis. Prior studies showed that there are alterations in the normal microbiome of the gut in patients with systemic sclerosis.

The authors sought to compare the specific GI microbiota of patients with and without systemic sclerosis, and compare separate cohorts who were geographically removed, while evaluating their hypothesis that specific microbial genera are associated with GI symptom severity. They presented their findings in a recent British Medical Journalarticle.

The study

Of 51 subjects enrolled in this prospective cohort study, 17 were healthy controls, 17 were patients with systemic sclerosis at UCLA, and 17 were patients with systemic sclerosis at Oslo University Hospital. Stool samples were taken from all subjects and analyzed.

The results

• The microbial composition of subjects with systemic sclerosis in both the UCLA and Oslo University cohorts differed significantly when compared with healthy controls (R2 0.355, p=0.001, and R2 0.126, p=0.002, respectively).

• Two dominant phyla of bacteria were found in systemic sclerosis subjects’ stool: Bacteroidetes (UCLA, 21.3%; Oslo, 45.0%; controls, 63.2%) and Firmicutes (UCLA, 21.3%; Oslo, 42.8%; controls, 33.0%).

Bacteroidetes numbers were significantly reduced in systemic sclerosis subjects when compared with healthy controls (UCLA, p<0.0001, and Oslo, p=0.009).

• Normal gut bacteria Faecalibacterium (UCLA), Clostridium (Oslo), and Bacteroides (UCLA, Oslo) were found in lower numbers in patients with systemic sclerosis compared with Fusobacterium (UCLA), Ruminococcus (UCLA), and the rare γ-Proteobacteria, Erwinia (UCLA), which were abundant in patients with systemic sclerosis when compared with healthy controls.

• The commensal bacteria Lactobacillus was more abundant in in subjects with systemic sclerosis.

• Systemic sclerosis subjects in Oslo had more Faecalibacterium and Bacteroides than subjects at UCLA.

• In both systemic sclerosis groups, Clostridium was more prominent in those with low GI symptom severity when compared with those who had high severity.

Lactobacillus was found in greater numbers in systemic sclerosis subjects who had mild or no constipation compared with those who had moderate or severe constipation.

Prevotella was more common in patients with moderate or severe GI symptoms than in patients with mild or no symptoms.

Implications for physicians

• Systemic sclerosis is associated with altered GI bacteria when compared with healthy subjects.

Bacteroidetes bacteria were depleted in patients with systemic sclerosis; the UCLA group had the lower numbers.

• Low levels of Bacteroidetes in systemic sclerosis may be associated with higher disease activity as is found with Crohn disease and other inflammatory diseases.

• The findings suggest that GI tract dysbiosis may be a pathological feature of the systemic sclerosis disease state.

• Specific genera of bacteria associated with GI dysfunction in systemic sclerosis may provide a target for treatment in this population.

Disclosures:

CURE: Digestive Research Center, the NIH, The Unger-Vetilesen Foundation, The Norwegian Women’s Public Health Association, Iris Cantor, the Health Authority of South-Eastern Norway, and the Norwegian Research Counsel provided funding for this project.

References:

Elizabeth R Volkmann, Anna-Maria Hoffmann-Vold, Yu-Ling Chang, et al. “Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.” BMJ Open Gastro. 2017;3: e000134. doi:10.1136/ bmjgast-2017-000134