Gastrointestinal mucositis (GI‐M) is a dose‐limiting complication of chemotherapy initiated by direct cytotoxic injury to the intestinal epithelium. It is then perpetuated by aberrant immune responses driven by the host and their microbiota. GI‐M presentation is heterogeneous, hypothesized to be influenced by patient factors including genomic variability, comorbidities, and, more recently, unique gut microbiota signatures. We aimed to identify microbial attributes that differ between patients that developed GI‐M compared with those that did not and use this information to identify/characterize novel microbial biotherapeutics. Archived stool samples collected from N = 12 patients undergoing standard‐dose chemotherapy were used. GI‐M was defined using the CTCAE. Microbial composition was assessed by 16S rRNA gene sequencing and the most differentially abundant taxon, Blautia luti, was identified for in vitro characterization. Blautia luti supernatants (BLSPNs) were isolated and investigated in vitro. Of the 12 patients recruited, four were included in the “high toxicity” group. B. luti levels strongly correlated with toxicity outcomes ( r = 0.744). Chemotherapy‐induced cell death in colonic epithelial cells was attenuated when treated prophylactically, concurrently, and therapeutically with BLSPN ( p = 0.0087, p = 0.0022, and p = 0.0166, respectively). Notably, 20% BLSPN enhanced Roseburia intestinalis ( p = 0.0015) and F. prausnitzii ( p = 0.0007) growth, but prevented Escherichia coli outgrowth ( p = 0.0002) under oxidative conditions. In conclusion, B. luti strongly correlates with GI‐M risk and demonstrates in vitro behaviors that address defined drivers of GI‐M etiology.
Secombe et al. (Thu,) studied this question.