The heme catabolite bilirubin has anti-inflammatory, anti-oxidative and anti-mutagenic effects and its relation to colorectal cancer (CRC) risk is currently under evaluation. Although the main metabolic steps of bilirubin metabolism, including the formation of stercobilin and urobilin, take place in the human gastrointestinal tract, potential interactions with the human gut microbiota are unexplored. This study investigated, whether gut microbiota composition is altered in Gilbert’s Syndrome (GS), a mild form of chronically elevated serum unconjugated bilirubin (UCB) compared to matched controls. Potential differences in the incidence of CRC-associated bacterial species in GS were also assessed. To this end, a secondary investigation of the BILIHEALTH study was performed, assessing 45 adults with elevated UCB levels (GS) against 45 age- and sex-matched controls (C). Fecal microbiota analysis was performed using 16S rRNA gene sequencing. No association between mildly increased UCB and the composition of the gut microbiota in this healthy cohort was found. The alpha and beta diversity did not differ between C and GS and both groups showed a typical representation of the known dominant phyla. Furthermore, no difference in abundance of Firmicutes and Proteobacteria, which have been associated with the mucosa of CRC patients were observed between the groups. A sequence related to the Christensenella minuta strain YIT 12065 was identified with a weak association value of 0.521 as an indicator species in the GS group. This strain has been previously associated with a lower body mass index, which is typical for the GS phenotype. Overall, sex was the only driver for an identifiable difference in the study groups, as demonstrated by a greater bacterial diversity in women. After adjusting for confounding factors and multiple testing, we can conclude that the GS phenotype does not affect the composition of the human gut microbiota in this generally healthy study group.

血红素分解代谢物胆红素具有抗炎、抗氧化和抗诱变作用，目前正在评估其与结直肠癌 (CRC) 风险的关系。虽然胆红素代谢的主要代谢步骤，包括粪胆素和尿胆素的形成，发生在人类胃肠道中，但与人类肠道微生物群的潜在相互作用尚未探索。这项研究调查了吉尔伯特综合征 (GS) 中肠道微生物群的组成是否发生了改变，与匹配的对照相比，这是一种慢性升高的血清未结合胆红素 (UCB) 的温和形式。还评估了 GS 中 CRC 相关细菌种类发生率的潜在差异。为此，对 BILIHEALTH 研究进行了二次调查，评估 45 名 UCB 水平升高 (GS) 的成年人与 45 名年龄和性别匹配的对照 (C)。使用 16S rRNA 基因测序进行粪便微生物群分析。在这个健康队列中，未发现轻度增加的 UCB 与肠道微生物群的组成之间存在关联。C 和 GS 之间的 alpha 和 beta 多样性没有差异，两组都显示出已知优势门的典型代表。此外，在丰度上没有差异厚壁菌 和 变形菌，这与 CRC 患者的黏膜有关。相关的序列小克里斯滕森菌菌株 YIT 12065 被鉴定为 GS 组中的指示物种，其弱关联值为 0.521。该菌株以前与较低的体重指数有关，这是 GS 表型的典型特征。总体而言，性别是研究组中可识别差异的唯一驱动因素，正如女性细菌多样性更大所证明的那样。在调整混杂因素和多重测试后，我们可以得出结论，在这个总体健康的研究组中，GS 表型不影响人类肠道微生物群的组成。