AUTHOR=Zöhrer Patrick A. , Hana Claudia A. , Seyed Khoei Nazlisadat , Mölzer Christine , Hörmann-Wallner Marlies , Tosevska Anela , Doberer Daniel , Marculescu Rodrig , Bulmer Andrew C. , Herbold Craig W. , Berry David , Wagner Karl-Heinz 

TITLE=Gilbert’s Syndrome and the Gut Microbiota – Insights From the Case-Control BILIHEALTH Study

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.701109

DOI=10.3389/fcimb.2021.701109

ISSN=2235-2988

ABSTRACT=The heme catabolite bilirubin has anti-inflammatory, anti-oxidative and anti-mutagenic effects and its relation to colorectal cancer risk (CRC) 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 for the first time the effect of Gilbert’s Syndrome (GS), a mild form of chronically elevated unconjugated serum bilirubin (UCB), on the gut microbiota and whether the incidence of CRC-associated bacterial species, previously identified in the literature, were influenced by GS. 
For that purpose, 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). Microbiota analysis in faecal samples was performed using 16S rRNA gene sequencing. 
No association between mildly increased serum 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 associated with a lower body mass index in literature, 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 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.