Recent Publication on the Gut Microbiome’s Role in Gout Features Atropos Health’s RWE
The choice of antibiotic may affect your gut microbiota which in turn influences uric acid metabolism and risk of gout. Atropos Health’s RWE capabilities supported the novel discovery of a widely distributed gene cluster integral to uric acid metabolism, and how uric acid metabolism may be influenced by antibiotics targeting different types of gut bacteria.
A recent preprint of the article “A widely distributed gene cluster compensates for uricase loss in hominids” (Liu et al.), https://www.biorxiv.org/content/10.1101/2022.07.24.501321v1.full, sought to understand whether aerobic vs anaerobic antibiotics might exacerbate the risk of hyperuricemia and gout, prevalent conditions affecting ~15% and ~4% of US adults, respectively. The authors hypothesized that patients on an anaerobic antibiotic (Clindamycin) would be at greater risk of developing gout compared to those on an aerobic antibiotic (Bactrim), since it targets anaerobic gut microbes involved in degrading uric acid and preventing hyperuricemia.
As such, Atropos Health was engaged to conduct a retrospective cohort study using de-identified EHR data from Stanford Health Care, leveraging our Advanced Cohorting Engine (ACE) and causal inference methods powered by high dimensional propensity scores. We compared new and recurrent gout diagnoses between new adult users of oral Clindamycin vs. oral Bactrim and found a higher risk of gout for Clindamycin-treated patients after propensity-score matching (hazard ratio=1.3, 95% CI, 1.1-1.54). After propensity score matching, the 2 treatment groups were similar in their baseline characteristics, (i.e. demography, sex distribution, and comorbidities).
These findings suggest that “disruption of the anaerobic gut microbiota by antibiotics increases the risk of developing gout in human patients”, supporting similar findings in uricase-knockout mice more sensitive to gut disruption.
Additionally, the mouse model demonstrated that uric acid metabolism in the gut might influence plasma levels in the host. Using isotope tracing and single knockout mutants of uric acid-inducible genes, the authors showed that gut bacteria with uric acid-inducible genes were critical for anaerobic uric acid metabolism. By identifying and characterizing these uric acid-inducible genes, the authors proposed a novel anaerobic mechanism for eliminating uric acid by gut bacteria.
The above results suggest two important implications:
First, antibiotic therapies that might disrupt the gut microbiota should be carefully considered in patients predisposed to gout
Second, increasing uric acid metabolism in the gut represents an important new therapeutic approach to treating patients with hyperuricemia
We envision that live biotherapeutic products consisting of uric acid consuming bacteria could be a new therapeutic modality to address outstanding needs in hyperuricemia and gout.
Atropos Health’s contributions to this publication are consistent with our commitment to leveraging our rapid, consistent real-world evidence generation capabilities to advance research and the practice of evidence-based medicine.
To learn more, get in touch with our team via info@atroposhealth.com.