Abstract
Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.
Highlights
Gout is an auto-inflammatory disease caused by a disorder in purine metabolism and the resulted chronic elevation of blood uric acid[1]
For each of the collectively 83 subjects, organismal structure of intestinal microbiota was analyzed by sequencing 16S ribosomal RNA (rRNA) gene amplicons, which revealed for each microbiota on average 202 operational taxonomic units (OTUs) from averagely 6402 reads (Supplementary Table 2)
To characterize the functional profiles of microbiota, 16 from the gout group, 18 from the healthy group and 5 from the validation group were randomly selected for whole-metagenome shotgun sequencing, yielding 371.2 Giga base (Gb) of pair-end reads
Summary
Gout is an auto-inflammatory disease caused by a disorder in purine metabolism and the resulted chronic elevation of blood uric acid (i.e., hyperuricemia)[1]. Uricase, allantoinase and allantoicase activities can sequentially degrade uric acid to 5-hydroxyisourate, allantoin, allantoate and eventually to urea Synthesis of these enzymes was found vigorous in Lactobacillus and Pseudomonas, both common members of human intestinal microbiota[18]. We hypothesize that the intestinal microbiota can potentially serve as proxy to probe uric acid metabolism in the host for the purpose of diagnosis or prognosis. To test this hypothesis, here we designed a cross-sectional study in an 83-member Chinese cohort that consists of both gout patients and healthy individuals. A microbiota-based model based on such difference was established and shown to diagnose gout at 88.9% accuracy
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