A recent study, led by Dr Heping Zhang from the Key Laboratory of Dairy Biotechnology and Bioengineering in China, has reported that early detection of gout may be possible through a diagnosis model that uses gout-associated bacteria.
Gout is an auto-inflammatory disease that has been rising worldwide. It is characterized by increased accumulation and reduced excretion of uric acid, which is the final product of purine metabolism. Current clinical diagnosis of gout is based on increased uric acid levels in the blood, although this is a measure with low sensitivity and late onset.
As humans excrete 30% of uric acid through the intestine, with intestinal bacteria participating in its metabolism, the researchers wondered if intestinal microbiota could potentially assist as an indicator of uric acid metabolism in the host for gout diagnosis.
The cross-sectional study included 83 Chinese adults. The gout group consisted of 35 adults and the control group consisted of 33 healthy adults. An additional validation group consisted of 6 gout patients and 9 healthy individuals. For all the participants, the taxonomic structure of their intestinal microbiota was determined by 16S rRNA gene pyrosequencing, and the functional profile of microbiota was analysed in a selected subsample within each group.
The gut microbiota composition was altered profoundly in gout patients, who showed a significant reduction in microbial diversity as compared to the healthy group. Potential confounding non-gout-related factors were taken into account in statistical analyses, and the results confirmed that the gout disease is a factor of major significance when explaining the difference in gut microbiota organismal structure in the gout group.
The gut microbiota functional profile of gout patients was also distinct from healthy individuals. Xanthine dehydrogenase enzyme that can degrade the purine to uric acid was enriched in the gout patients, whereas the allantoinase that degrades the uric acid to urea was depleted. This mechanism contributes to increasing levels of uric acid, which cannot be further degraded to urea, resulting in accumulation of uric acid and consequent aggravation of gout symptoms.
To investigate microbial species linked to gout, microbial genes were grouped into clusters based on their abundance. The metagenomic species network was differently enriched in gout patients and healthy individuals. In gout patients, Bacteroides caccae and B. xylanisolvens were enriched, whereas Faecalibacterium prausnitzii, Clostridium butyrate-producing bacteria and Bifidobacterium pseudocatenulatum were depleted. B. caccae is thought to potentially induce an inflammatory response in gout patients. F. prausnitzii depletion may be detrimental and could explain the decline in butyric acid biosynthesis in gout patients, as it is a beneficial bacterium due to its anti-inflammatory effects and its major role in maintaining gut health through butyrate production. A total of 17 genera were associated with the gout, and these could be considered microbial biomarkers of the gout disease. Researchers developed a ‘microbial index of gout’ (MiG) based on the relative abundance of those specific bacterial markers that distinguish gout patients from healthy controls. In the validation group, a diagnosis model using the MiG reached 88.9% accuracy, which was higher than that based on measurement of uric acid in the blood (71.3%).
To sum up, the Microbial index of Gout is proposed as a novel and sensitive tool for early diagnosis of gout via faecal microbiota. If validated in larger cohorts, including measurements of intestinal microbiota in the diagnosis of gout could provide new ways to prevent and control gout.
Guo Z, Zhang J, Wang Z, et al. Intestinal microbiota distinguish gout patients from healthy humans. Sci Rep. 2016; 6:20602. doi:10.1038/srep20602.