Abstract
Metabolic impairments are a frequent hallmark of systemic lupus erythematosus (SLE). Increased serum levels of free fatty acids (FFA) are commonly found in these patients, although the underlying causes remain elusive. Recently, it has been suggested that factors other than inflammation or clinical features may be involved. The gut microbiota is known to influence the host metabolism, the production of short-chain fatty acids (SCFA) playing a potential role. Taking into account that lupus patients exhibit an intestinal dysbiosis, we wondered whether altered FFA levels may be associated with the intestinal microbial composition in lupus patients. To this aim, total and specific serum FFA levels, fecal SCFA levels, and gut microbiota composition were determined in 21 SLE patients and 25 healthy individuals. The Firmicutes to Bacteroidetes (F/B) ratio was strongly associated with serum FFA levels in healthy controls (HC), even after controlling for confounders. However, this association was not found in lupus patients, where a decreased F/B ratio and increased FFA serum levels were noted. An altered production of SCFA was related to the intestinal dysbiosis in lupus, while SCFA levels paralleled those of serum FFA in HC. Although a different serum FFA profile was not found in SLE, specific FFA showed distinct patterns on a principal component analysis. Immunomodulatory omega-3 FFA were positively correlated to the F/B ratio in HC, but not in SLE. Furthermore, divergent associations were observed for pro- and anti-inflammatory FFA with endothelial activation biomarkers in lupus patients. Overall, these findings support a link between the gut microbial ecology and the host metabolism in the pathological framework of SLE. A potential link between intestinal dysbiosis and surrogate markers of endothelial activation in lupus patients is supported, FFA species having a pivotal role.
Highlights
Epidemiological studies have consistently shown an increase in the prevalence and severity of a number of metabolic disorders in patients with systemic lupus erythematosus (SLE) compared to the general population [1,2,3]
The main aims of the present report were (i) to analyze the potential association between the microbiota composition and free fatty acids (FFA) serum levels, (ii) to elucidate whether microbial metabolites can have a role in this interaction, (iii) to evaluate whether a different profile of FFA can be found in lupus patients, and (iv) to study the associations of these parameters with clinically relevant serum biomarkers
The concentration of total FFA was measured in serum samples from 21 SLE patients and 25 matched healthy controls (HC) (Table 1)
Summary
Epidemiological studies have consistently shown an increase in the prevalence and severity of a number of metabolic disorders in patients with systemic lupus erythematosus (SLE) compared to the general population [1,2,3]. These mediators can impair the balance between endothelial repair and damage, whereas a number of systemic effects can be triggered, including a shift to a pro-oxidant status [8] and altered lipid metabolism. In this scenario, the underlying mechanisms are not totally understood, the relationship between systemic inflammation, metabolic disorders, and CVD may be explained, at least in part, by the free fatty acids (FFA) [9]. These clinical studies did not allow the elucidation of the exact mediators and mechanisms involved
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