Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients

Abstract

Background Currently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs. Methods Fecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients. Results P-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis. Conclusions PPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

Let’s review the gut microbiota in systemic lupus erythematosus

“…Similarly to the results in mouse studies, in humans the alpha-diversity alterations were also heterogeneous, varying between lower alpha-diversity [20,26,32,33,35,37,39,41,42], increased alpha-diversity [30] or no alterations in this marker compared with HC [16,19,27,31,34]. No differences were found between the newly onset patients and other patients, nor between patients with and without LN [35].…”

“…The beta-diversity was altered between SLE patients and controls [16,27,30,32,35,[37][38][39]41], but not in all studies [31]. Although no association was found with medication [32], some authors found that after PPI use, there was an approximation between the microbiota profile of SLE patients with HC [39].…”

“…The beta-diversity was altered between SLE patients and controls [16,27,30,32,35,[37][38][39]41], but not in all studies [31]. Although no association was found with medication [32], some authors found that after PPI use, there was an approximation between the microbiota profile of SLE patients with HC [39]. Beta-diversity also varied between patients with low and high disease activity [37,38], although not consensually [35], and before and after disease onset [22,42].…”

“…A total of 29 studies were included in this review, twelve of which used mouse models [14][15][16][17][18][19][20][21][22][23][24][25], fifteen included SLE patients [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], and two both [41,42].…”

“…Additionally, a GWAS involved 7,219 SLE cases and 15,991 HC [29]. Ten studies included Chinese populations [26,27,[30][31][32][33][39][40][41], one Egyptian [28], two American [37,42], one Spanish [34], one Japanese [35], and one Dutch [38]. The mean age of the participants ranged between 12.4 and 49.2 years old for SLE patients and 10.6 and 46.9 years old for HC.…”