Gastrointestinal tract involvement in systemic sclerosis: The roles of diet and the microbiome

Elsevier

Available online 24 February 2023, 152185

Seminars in Arthritis and RheumatismAuthor links open overlay panel, , , , , , , , AbstractBackground

Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype.

Objectives

Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet.

Methods

Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet.

Results

Of the 66 total SSc patients included, the majority were women (n=56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N=19) versus non-low (N=16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus.

Conclusion

SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.

Section snippetsINTRODUCTION

Systemic sclerosis (SSc) is a rare, incurable autoimmune disease with the highest cause-specific mortality of all connective tissue diseases [1,2]. The gastrointestinal (GI) tract is one of the most commonly affected internal organs in SSc, [3] and involvement of the GI tract is a leading cause of morbidity and mortality in SSc [4,5].

The pathogenesis of GI involvement in SSc is poorly understood. Recent studies have found significant differences in GI microbial composition between SSc patients

Study Participants

Patient participants were consecutively enrolled from outpatient rheumatology clinics at the University of California, Los Angeles (UCLA). Inclusion criteria were: (1) adult patients (age ≥18 years); (2) SSc of any disease duration according to the 2013 American College of Rheumatology/European League Against Rheumatism Classification Criteria for SSc [15]. Exclusion criteria were: (1) co-morbid GI condition, including inflammatory bowel disease (IBD), celiac disease and GI malignancy; (2)

Participant Characteristics

Among the 66 participants enrolled in this study, the majority were women with a mean age of 55 ± 11.8 years (Table 1). The mean disease duration was 9.6 years, and there was a similar balance of patients with diffuse and limited cutaneous sclerosis. Most participants (84%) were taking immunosuppressants at the time of stool collection. No participants had received antibiotics during the four weeks prior to stool collection. No participants received antibiotics more than 2 times in the

DISCUSSION

This study demonstrated that decreased microbial diversity (e.g., alpha diversity) is associated with more severe SSc-GI symptoms. Specifically, patients with less microbial diversity reported worse GI morbidity and worse symptoms of distension and social functioning. Patients with increased GI symptom severity also exhibited differences in overall microbial composition (e.g., beta diversity) from those with less severe GI symptoms. Moreover, pathobiont genera (e.g., Enteroccocus, Klebsiella)

CONCLUSIONS AND FUTURE DIRECTIONS

In summary, SSc patients reporting more severe GI symptoms exhibited signs of GI microbial dysbiosis characterized by reduced species richness and altered microbial composition. While a low FODMAP diet was not associated with reduced symptom severity or altered microbial composition compared to a non-low FODMAP diet, certain pathobiont phylotypes were enriched in the non-low FODMAP group. Understanding the relationships between alterations in GI microbial composition and SSc may help identify

AUTHOR CONTRIBUTIONS

Audrey Nguyen: data analysis and interpretation; drafted and critically reviewed the article; study design; agrees to the journal to which the article will be submitted; reviewed and agreed on article version for submission; agrees to take responsibility and be accountable for article contents.

Kristofer Andréasson: study design; data analysis and interpretation; critically reviewed and edited the article; agrees to the journal to which the article will be submitted; reviewed and agreed on

FUNDING

This work was supported by NHLBI (K23 HL150237-01 [ERV]; Greg Cohen [ERV]; Anonymous donor [ERV]; VA CDA2 IK2CX001717 [JPJ]; Ulla and Roland Gustafssons donations fund [KA]; NIH/NIAMS K23 AR071473, Scleroderma Research Foundation, Rheumatology Research Foundation, Jerome L Greene Foundation [ZHM].

Declaration of Competing Interest

None.

Acknowledgements

None.

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