Strongyloides stercoralis infection induces gut dysbiosis in chronic kidney disease patients

Abstract

Background: Strongyloides stercoralis infection typically causes severe symptoms in immunocompromised patients. This infection can also alter the gut microbiota and is often found in areas where chronic kidney disease (CKD) is common. However, the relationship between S. stercoralis and the gut microbiome in chronic kidney disease (CKD) is not understood fully. Recent studies have shown that gut dysbiosis plays an important role in the progression of CKD. Hence, this study aims to investigate the association of S. stercoralis infection and gut microbiome in CKD patients.

Methodology/principal findings: Among 838 volunteers from Khon Kaen Province, northeastern Thailand, 40 subjects with CKD were enrolled and divided into two groups (S. stercoralis-infected and -uninfected) matched for age, sex and biochemical parameters. Next-generation technology was used to amplify and sequence the V3-V4 region of the 16S rRNA gene to provide a profile of the gut microbiota. Results revealed that members of the S. stercoralis-infected group had lower gut microbial diversity than was seen in the uninfected group. Interestingly, there was significantly greater representation of some pathogenic bacteria in the S. stercoralis-infected CKD group, including Escherichia-Shigella (P = 0.013), Rothia (P = 0.013) and Aggregatibacter (P = 0.03). There was also a trend towards increased Actinomyces, Streptococcus and Haemophilus (P > 0.05) in this group. On the other hand, the S. stercoralis-infected CKD group had significantly lower representation of SCFA-producing bacteria such as Anaerostipes (P = 0.01), Coprococcus_1 (0.043) and a non-significant decrease of Akkermansia, Eubacterium rectale and Eubacterium hallii (P > 0.05) relative to the uninfected group. Interesting, the genera Escherichia-Shigella and Anaerostipes exhibited opposing trends, which were significantly related to sex, age, infection status and CKD stages. The genus Escherichia-Shigella was significantly more abundant in CKD patients over the age of 65 years and infected with S. stercoralis. A correlation analysis showed inverse moderate correlation between the abundance of the genus of Escherichia-Shigella and the level of estimated glomerular filtration rate (eGFR).

Conclusions/significance: Conclusion, the results suggest that S. stercoralis infection induced gut dysbiosis in the CKD patients, which might be involved in CKD progression.

Fig 1. Species accumulation curve.

X-axis: Number of samples, Y-axis: number of OTUs. Following an initial sharp rise in the number of OTUs as number of samples increases, there is a levelling of the plot. The narrow spread of the boxplots as the total number of samples is approached indicates that the number of samples was adequate to capture most of the microbial diversity present.

Fig 2. Comparison of alpha diversity indexes and beta diversity in CKD patients with and without S. stercoralis infection.

(A) Shannon index (B) Shannon index in males (C) Simpson index in males. (D) Boxplot based on unweighted UniFrac distance. (E) Principal coordinate analysis (PCoA).

Fig 3. Histogram of cladogram and linear discriminant analysis (LDA) score.

The histogram of the LDA scores presents taxa (potential biomarkers) whose abundance differed significantly among groups (Ss+ vs. Ss-) order Bradymonadales in Ss- (green color). Species E. coli belongs to the genus Escherichia-Shigella; genus Dialister belongs to the order Selenomonadales, class Negativicutes and family Veillonellaceae in Ss+ (red color). The cladogram shows specific taxa relevant to Ss+ and Ss- in the red and green nodes. The highest taxonomic level is towards the center of the diagram. The diameter of each circle represents the relative abundance of the taxon.

Fig 4. The gut microbiota composition.

(A) and (B), Control group compared with S. stercoralis-infection group (Ss+) at the phylum and genus levels, respectively.

Fig 5. Clustering using the unweighted pair group method with arithmetic mean (UPGMA).

UPGMA cluster tree based on unweighted UniFrac distances between CKD patients with or without S. stercoralis infection. The red branches represent individuals with S. stercoralis infection (Ss+) and the dark blue branches indicate uninfected (Ss-) individuals.

Fig 6. Comparisons of abundance (numbers of sequence reads) of some bacteria between Ss- and Ss+ group.

Pathogenic bacteria: Escherichia-Shigella, Streptococcus, Haemophilus, Rothia, Actinomyces, Aggregatibacter. SCFA-producing bacteria: Eubacterium rectale_group, Eubacterium hallii_group, Anaerostipes, Coprococcus_1, Akkermansia.

Fig 7. Opposing trends in abundance of two genera, Anaerostipes and Escherichia-Shigella.

(A) and (D) Different trends related to age; (B) and (E) sex; (C) and (F) CKD stages. * P < 0.05, **P < 0.01, ***P < 0.001. Analysis of the difference among groups of sex, age and CKD stages based on one-way ANOVA test.