Session Item

A mono-institutional trial was set up in 2017 to investigate the modulations of gut microbiota (MB) after prostate cancer (PCa) radiotherapy (RT). We here explore how RT can modulate MB species abundances, but also the possibility that urinary (GU) and intestinal (GI) toxicity (tox) is associated to different modulations in MB

Consecutive patients (pts) receiving conventional (70-78Gy @2Gy/fr) or moderately hypofractionated (65-67.5Gy @2.6Gy/fr) VMAT+IGRT were enrolled. Gut MB was measured pre-RT and at RT end.  Stool samples were collected using gut-OMNIgene devices, DNA extracted using the QIAamp-DNA-Stool-Mini-Kit, bacterial 16S ribosomal-RNA reads analyzed with QIIME software and pooled in Operational Taxonomic Units (OTU) with Uclust software. Pre-RT and post-RT OTUs at genus and species taxonomic levels were considered. Modulation was  evaluated by Wilcoxontest, both on the whole population and after stratification with respect to acute GU and GI tox (CTCAE): Grade 0 (G0) vs Grade 1 (G1) vs Grade 2 (G2)

135 pts were included, 157 genera and 412 bacterial species were identified. 59/157 genera and 132/412 species were found in at least 10% of pts and included in the analyses. 7 genera (Bilophila, Faecalibacterium, Flavonifractor, Gemmiger, Phascolarctobacterium, Roseburia, Sutterella) and 4 species (Blautia producta, Faecalibacterium prausnitzii, Roseburia faecis, Ruminococcos bromii) were significantly modulated by RT (p<0.01 and <0.001, for genera and species, respectively), details in fig 1. Of interest, Ruminococcus bromii is a keystone species for the degradation of resistant starch in the colon and a possible relationship between Roseburia faecis and irritable bowel syndrome was recently proposed. When considering GI tox, 29 (22%), 30 (22%) and 76 (56%) pts reported G0, G1 and G2 events, respectively. No significant MB modulation was found in G0 (at p level<0.01), while 7 genera were significantly modulated by RT in G1: Faecalibacterium, Flavonifractor, Gemmiger, Odoribacter, Phascolarctobacterium, Roseburia, Sutterella (p range: 0.003-0.008). 3 genera were significantly modulated in G2: Akkermansia, Bilophila, Faecalibacterium (p range: 0.001-0.008). When considering GU tox, 80 (59%) and 42 (31%) pts reported G1 and G2 events, respectively. No significant MB modulation (at p level<0.01) in G0 was identified.5 genera were modulated in G1: Faecalibacterium, Flavonifractor, Phascolarctobacterium, Ruminococcus, Sutterella (p<0.01). Lactobacillus was significantly modulated exclusively in pts with G2 GU tox (p=0.008). The detailed results about association between tox and MB species are reported in fig 2

This analysis demonstrated the possibility to quantitatively study RT-induced alteration of gut MB in a clinical setting including “real world” pts. Moreover, association between acute tox and different pattern of MB alteration was highlighted: a dysbiotic MB becomes a strongly suspected actor in appearance and evolution of RT-induced tox