Esophageal Dysmotility and Gut Microbiome Alterations in Systemic Sclerosis

Abstract

Background and Aims : Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by widespread fibrosis and vascular abnormalities that affect multiple organs, including the gastrointestinal tract. Esophageal dysmotility (ED), a common complication of SSc, significantly impairs patients’ quality of life and contributes to morbidity and mortality. Concurrently, alterations in gut microbiota composition referred to as dysbiosis, have been observed in SSc patients. This review aims to synthesize current literature on the relationship between ED and gut microbiome alterations in SSc, exploring potential pathophysiological links and therapeutic implications. Methods : A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, using keywords such as “systemic sclerosis,” “esophageal dysmotility,” “gut microbiota,” and “dysbiosis.” Studies examining gut microbiome composition and function in SSc patients with ED were included. This review prioritizes human studies employing high-resolution manometry (HRM), esophageal transit studies, 16S rRNA gene sequencing, metagenomics, and metabolomics. Studies were assessed for methodological quality and potential biases. Extracted data included the prevalence of ED and specific patterns of dysbiosis observed in SSc patients. Results : A high prevalence of ED was reported among SSc patients, ranging from 50% to 90% across different studies. The severity of ED varied, spanning from ineffective esophageal motility to complete absence of contractility. Multiple studies identified significant alterations in the gut microbiome of SSc patients compared to healthy controls. These alterations included a decreased abundance of beneficial bacteria such as Faecalibacterium , Clostridium , and Bacteroides , alongside an increased prevalence of potentially pathogenic bacteria like Fusobacterium , Prevotella , and Erwinia . The specific composition of gut microbiota varied across studies, likely influenced by factors such as SSc subtype (limited vs. diffuse cutaneous SSc), disease duration, and treatment regimens. Several studies investigated the correlation between gut microbiome alterations and specific gastrointestinal symptoms, including dysphagia. However, the causal relationship between gut dysbiosis and ED remains uncertain. Some evidence suggests that dysbiosis may contribute to inflammation and fibrosis in the esophagus, exacerbating ED, while other findings propose that ED may induce secondary changes in gut microbiota due to altered motility and nutrient absorption. Conclusion : This review underscores the strong association between ED and gut microbiome alterations in SSc. The high prevalence of ED and the consistent findings of dysbiosis suggest a complex interplay between these two factors. However, further research is necessary to elucidate the precise mechanisms underlying their relationship, particularly whether dysbiosis is a cause, consequence, or contributing factor to ED. Future studies should prioritize longitudinal investigations, mechanistic studies exploring interactions between gut microbiota, immune responses, and esophageal tissue, and well-designed clinical trials assessing microbiome-targeted therapies for ED in SSc.