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. 2025 Nov;7(11):e70127.
doi: 10.1002/acr2.70127.

Characterization of the Fecal Metabolome in Patients With Early Systemic Sclerosis

Arissa C Young  1 , Kristofer Andréasson  2 , Jennifer Labus  1 , Nedas Matulionis  1 , Jonathan P Jacobs  1 , Heather Christofk  1 , Elizabeth R Volkmann  1
Affiliations

Characterization of the Fecal Metabolome in Patients With Early Systemic Sclerosis

Arissa C Young et al. ACR Open Rheumatol. 2025 Nov.

Abstract

Objective: To evaluate the fecal metabolome in patients with early systemic sclerosis (SSc) compared with unaffected controls and to determine if altered metabolites are associated with specific bacterial genera in patients with early SSc.

Methods: Stool samples and clinical data were collected from 106 patients with early SSc and 79 unaffected control patients. Targeted metabolomics was performed on fecal samples using liquid chromatography mass spectrometry, and 16S ribosomal RNA gene sequencing was used to determine the microbial composition of fecal samples.

Results: Compared with unaffected controls, patients with early SSc had higher levels of nicotinamide, 5'-methylthioadenosine, and several short-chain fatty acids (SCFAs) including valeric acid, propionic acid, and caproic acid. Conversely, patients with early SSc had lower levels of xylonic acid, orotate, methionine sulfoxide, and sarcosine. SCFAs were associated with unique bacterial genera, several of which were more abundant in patients with SSc compared with unaffected controls.

Conclusion: The fecal metabolome is altered in patients with early SSc, with a shift toward increased SCFAs.

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Figures

Figure 1
Figure 1
Patients with early SSc (blue) have increased abundance of specific short‐chain fatty acids compared with unaffected controls (red). SSc, systemic sclerosis.
Figure 2
Figure 2
Sparse partial least squares discriminant analysis for differentiating SSc from unaffected controls based on fecal metabolome. (A) Orange bars indicate metabolites that are more abundant in patients with early SSc compared with controls. Blue bars indicate metabolites that are more abundant in controls compared with early SSc. (B) The classification performance of sparse partial least squares discriminant analysis in part A when applied to patient samples. Unaffected controls are represented by blue circles, and SSc patients are represented by orange triangles. CMP, cytidine monophosphate; GMP, guanosine monophosphate; SSc, systemic sclerosis.
Figure 3
Figure 3
Forest plot showing significant associations (Q < 0.05) between gut bacteria (genus‐level taxa) and SCFAs after adjusting for age, sex, small intestinal bacterial overgrowth, body mass index, proton pump inhibitor, and any immunosuppression. Red dots indicate negative associations, and blue dots indicate positive associations. Bacterial genera that are outlined in green are more abundant in patients with SSc. Bacterial genera that are outlined in orange are more abundant in unaffected controls. CI, confidence interval; SCFA, short‐chain fatty acid.
Figure 4
Figure 4
Patients with early SSc (red) have an increased abundance of bacteria that are positively associated with short‐chain fatty acids and a decreased abundance of bacteria that are negatively associated with short‐chain fatty acids. SSc, systemic sclerosis.
See this image and copyright information in PMC

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