Department of Medicine, Nephrology Division, Duke University Medical Center, Durham, NC, USA.
Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
Ann Med. 2022 Dec;54(1):1221-1225. doi: 10.1080/07853890.2022.2069853.
Accumulating evidence suggest that gut microbiota may impact urologic health including prostate cancer (PC), potentially 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 >3 and <36 months, and body mass index (BMI) ≥24 kg/m.
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%; = .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( = .003). There was a similar inverse trend between change in zonulin and log(PSADT) ( = .050). Nevertheless, the mediation analysis showed that zonulin was not a significant intermediary mechanism of the effect of weight change on PSADT ( = .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. 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.
越来越多的证据表明，肠道微生物群可能会影响泌尿科健康，包括前列腺癌（PC），可能会影响肠道通透性（IP）。研究表明，健康饮食和减肥可以改善受损的肠道通透性。在 Carbohydrate and Prostate Study 2（CAPS2）临床试验中，低碳水化合物饮食（LCD）显著降低了 PC 患者的体重，并暗示减缓了 PC 疾病的进展，我们探讨了 LCD 对肠道通透性标志物——紧密连接蛋白（zonulin）和炎症标志物——高敏 C 反应蛋白（hsCRP）的影响。
CAPS2 是一项为期 6 个月的随机对照试验，使用前列腺特异性抗原倍增时间（PSADT）作为标志物，测试了 LCD 干预与对照组在 PC 进展方面的效果。所有 45 名参与者均接受过初次 PC 治疗，PSADT＞3 且＜36 个月，且体重指数（BMI）≥24kg/m。
在 6 个月时，LCD 组 zonulin 降低（中位数-8.3%，IQR-16.6，0.3%），而对照组略有增加（中位数 1.4%，IQR-3.0，13.3%； = .014）。hsCRP 无变化。线性回归模型显示，体重变化与 log(PSADT)显著相关，体重减轻越多，PSADT 越长（ = .003）。zonulin 与 log(PSADT)的变化呈类似的反向趋势（ = .050）。然而，中介分析表明，zonulin 不是体重变化对 PSADT 影响的重要中介机制（ = .3）。
未来的研究值得进一步探讨肠道通透性与炎症的潜在关联，并阐明肠道通透性的改善是否与 PC 进展的减缓有关。NCT01763944。关键信息肠道微生物群可能会影响泌尿科健康，包括前列腺癌，可能通过影响肠道通透性。体重减轻显著改善了前列腺癌患者的肠道通透性。肠道通透性的改善与 PSA 倍增时间表明的前列腺癌进展减缓相关。
