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Accumulating evidence suggest that gut microbiota may impact urologic health including prostate cancer (PC), potentially  via  affecting intestinal permeability (IP). Studies have indicated that disrupted IP may be improved by healthy diets and weight loss. In the Carbohydrate and Prostate Study 2 (CAPS2) clinical trial, which showed that a low-carbohydrate diet (LCD) reduced weight significantly in men with PC and suggestively slowed PC disease progression, we explored the impact of LCD on an IP marker, zonulin and an inflammation marker, high sensitivity C-reactive protein (hsCRP). CAPS2 was a 6-month randomized controlled trial testing a LCD intervention vs. control on PC progression using prostate-specific antigen doubling time (PSADT) as the marker. All 45 participants had prior primary PC treatment, PSADT &gt;3 and &lt;36 months, and body mass index (BMI) ≥24 kg/m 2 . At 6-month, zonulin decreased in the LCD arm (median −8.3%, IQR −16.6, 0.3%) while the control increased slightly (median 1.4%, IQR −3.0, 13.3%;  p  = .014). No changes were observed in hsCRP. Linear regression models showed that weight change was significantly associated with log(PSADT) such that the greater the weight loss, the longer the PSADT( p  = .003). There was a similar inverse trend between change in zonulin and log(PSADT) ( p  = .050). Nevertheless, the mediation analysis showed that zonulin was not a significant intermediary mechanism of the effect of weight change on PSADT ( p  = .3). Future studies are merited to examine further the potential association of IP with inflammation and to clarify if improvement in IP is associated with decreased PC progression.  Trial registration:  NCT01763944.KEY MESSAGESGut microbiota may impact urologic health including prostate cancer, potentially via affecting intestinal permeability.Weight loss significantly improved intestinal permeability in prostate cancer patients.Improvement in intestinal permeability was associated with slowed prostate cancer progression as indicated by the PSA doubling time. Gut microbiota may impact urologic health including prostate cancer, potentially via affecting intestinal permeability. Weight loss significantly improved intestinal permeability in prostate cancer patients. Improvement in intestinal permeability was associated with slowed prostate cancer progression as indicated by the PSA doubling time.

Weight loss via a low-carbohydrate diet improved the intestinal permeability marker, zonulin, in prostate cancer patients