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. 2024 Jan 10;12(1):148.
doi: 10.3390/biomedicines12010148.

Exploring the Relationship between Gut Microbiome Composition and Blood Indole-3-acetic Acid in Hemodialysis Patients

Ping-Hsun Wu  1   2   3   4 , Yu-Fang Tseng  5 , Wangta Liu  6 , Yun-Shiuan Chuang  3   4   7 , Chi-Jung Tai  7 , Chun-Wei Tung  8   9 , Kean-Yee Lai  10 , Mei-Chuan Kuo  1   2 , Yi-Wen Chiu  1   2 , Shang-Jyh Hwang  1   2 , Wei-Chun Hung  11 , Yi-Ting Lin  2   3   4   7
Affiliations

Exploring the Relationship between Gut Microbiome Composition and Blood Indole-3-acetic Acid in Hemodialysis Patients

Ping-Hsun Wu et al. Biomedicines. .

Abstract

Indole-3-acetic acid (IAA), a protein-bound uremic toxin resulting from gut microbiota-driven tryptophan metabolism, increases in hemodialysis (HD) patients. IAA may induce endothelial dysfunction, inflammation, and oxidative stress, elevating cardiovascular and cognitive risk in HD patients. However, research on the microbiome-IAA association is limited. This study aimed to explore the gut microbiome's relationship with plasma IAA levels in 72 chronic HD patients aged over 18 (August 2016-January 2017). IAA levels were measured using tandem mass spectrometry, and gut microbiome analysis utilized 16s rRNA next-generation sequencing. Linear discriminative analysis effect size and random forest analysis distinguished microbial species linked to IAA levels. Patients with higher IAA levels had reduced microbial diversity. Six microbial species significantly associated with IAA levels were identified; Bacteroides clarus, Bacteroides coprocola, Bacteroides massiliensi, and Alisteps shahii were enriched in low-IAA individuals, while Bacteroides thetaiotaomicron and Fusobacterium varium were enriched in high-IAA individuals. This study sheds light on specific gut microbiota species influencing IAA levels, enhancing our understanding of the intricate interactions between the gut microbiota and IAA metabolism.

Keywords: end-stage kidney disease; hemodialysis; indole-3-acetic acid; microbiome.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The α-diversity and β-diversity in hemodialysis patients with high and low levels of indole-3-acetic acid (IAA). (A) Patients with high IAA levels presented a higher α-diversity (species richness index and species evenness index) than patients with low IAA levels. The star mark ** referred to p-value <0.05 (B) Patients with high IAA levels had a different β-diversity (Bray–Curtis index) compared to patients with low IAA levels. The β-diversity p-value was calculated using homogeneity of group dispersions by analysis of similarities (ANOSIM) test and permutational multivariate analysis of variance (PERMANOVA) test.
Figure 2
Figure 2
Taxonomic differences were detected between patients with low and high levels of indole-3-acetic acid. Cladogram showing differentially abundant taxonomic clades with an LDA score > 3.0 among patients with low and high levels of indole-3-acetic acid.
Figure 3
Figure 3
Determination of bacteria specific for discrimination across low and high levels of indole-3-acetic acid in hemodialysis patients by applying random forest analysis at the (A) genus-level abundance and (B) species-level abundance. The star sign *** referred to the significant difference in abundance with p-value < 0.05.
Figure 4
Figure 4
The correlation between IAA-associated Bacteroides species and sex, age, albumin, BUN, creatinine, glucose, potassium, LDL, sodium, nPCR, phosphate, total calcium, and uric acid in hemodialysis patients. * indicated p < 0.05.
See this image and copyright information in PMC

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