Study: Fecal Microbiome More Diverse in SSc Patients

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by Patricia Inacio PhD |

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The fecal microbiome — the community of microbes present in stools — of scleroderma patients is more diverse than that of healthy people, according to a Canadian study.

The findings also showed that the diversity and abundance of bacterial species in the stools was higher among patients with an abnormal increase in the overall bacterial population in the small intestine.

The study, “Fecal microbiome differs between patients with systemic sclerosis with and without small intestinal bacterial overgrowth,” was published in the Journal of Scleroderma and Related Disorders.

Up to 90% of patients with scleroderma — or systemic sclerosis (SSc) — experience gastrointestinal (GI) tract symptoms such as diarrhea and constipation. Despite representing the second-most commonly affected system, the cause for GI symptoms in scleroderma remains elusive.

Prior research, however, suggested that alterations in scleroderma patients’ fecal microbiome may play a role.

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Small intestinal bacterial overgrowth (SIBO), a condition associated with increased numbers of bacteria in the small intestine, was detected in 43% of scleroderma patients in a prior study.

Now, researchers at the McMaster University, in Canada, analyzed the fecal microbiome of scleroderma patients and compared it between those with and without a diagnosis of SIBO, as well as to that of healthy people, who served as controls.

In total, the study included 29 patients (27 women, two men, mean age 55.5 years). Thirteen had SIBO (44.8%). There were 20 healthy controls (14 women, six men, mean age 33.1). Limited cutaneous scleroderma was the most prevalent type of the disorder, seen in 20 of the 29 patients. Also, most patients (69%) were positive for anticentromere autoantibodies (ACA), the characteristic antibodies in scleroderma that wrongly target the body’s own tissues.

Patients underwent breath testing to assess SIBO. All participants provided stool samples for analysis and completed the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (GIT 2.0). That tool is used to evaluate GI tract manifestations and health-related quality of life. Higher scores indicate worse symptoms.

Results revealed that the fecal microbiome of scleroderma patients was more diverse than that of healthy controls. Specifically, patients had a higher abundance of two groups (phylum) of bacteria — called Proteobacteria and Bacteroidetes — but fewer of the phylum called Firmicutes.

At the genera level, which is organized under the pylum, the patients had lower abundance of bacteria from the genus Enterocococcus, Lactococcus, and SMB53.

The researchers compared the fecal microbiome of patients positive for SIBO to that of controls. The analysis revealed differences in relative bacterial diversity — such as a larger abundance of Bacteroides bacteria — but the absolute number (abundance) of species was similar.

Bacteroides bacteria “have been shown to negatively affect GI symptoms in SSc over time when in low abundance,” the researchers wrote.

No differences were observed between SIBO-negative SSc patients and healthy controls.

Also, when assessing patients relative to their SIBO status, the results showed that both diversity and abundance of bacterial species were higher in those with SIBO.

No correlations were seen between participants without ACA or those with another type of characteristic scleroderma antibodies, known as anti-Scl-70 autoantibodies, and breath testing or specific bacteria.

However, in patients positive for ACA autoantibodies, a higher relative abundance of the species Alistipes indistinctus was associated with higher methane levels in their breath. Also, in these patients a higher burden of GI symptoms associated with increased abundance of the bacterium Coprobacillus cateniformis.

Lower abundance of Clostridium bacteria corelated with worse emotional well-being. In contrast, a higher abundance of Slackia bacteria was linked with higher rates of fecal soiling (incontinence).

Overall, “this study identified unique microbiota profiles in patients with SSc in comparison with HCs [healthy controls], as well as differences in microbial composition in SIBO- positive versus SIBO-negative SSc patients,” the researchers wrote.

“Furthermore, we have found novel associations between certain bacterial taxa [ranks] and emotional well-being in SSc,” they added.

Among the study’s limitations, the investigators mentioned that the controls were not matched to the patients in their age, lifestyle habits, and ethnicity. Not being able to analyze the microbiome over time was another limitation.

“While a larger sample size is needed to validate these results, they provide potential bacterial targets for therapies aimed at improving the GI symptoms and quality of life in patients with SSc,” they concluded.