Microbiome-based probiotic intervention to reduce chemotherapy-induced gastrointestinal toxicity

Chemotherapy is one of the primary treatment options for cancer; however, its gastrointestinal toxicity and disruption of gut microbial homeostasis can adversely affect patient health and treatment outcomes. This study investigated chemotherapy-induced alterations in the gut microbiome and evaluated the effects of probiotic supplementation on microbial diversity, gastrointestinal toxicity, and treatment response in cancer patients.

The probiotic strain was isolated from a commercial formulation and identified as Lactobacillus casei using biochemical characterization and 16S rRNA gene sequencing. Its secreted metabolites were characterized using Fourier-transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy. A total of 150 patients receiving platinum-based chemotherapy were enrolled and divided into control and probiotic intervention groups. Fecal samples were collected before and after chemotherapy and subjected to 16S rRNA sequencing to assess microbial diversity and taxonomic composition.

Chemotherapy induced significant gut microbial dysbiosis, characterized by reduced alpha diversity, decreased abundance of beneficial bacteria, including Lactobacillus, Bifidobacterium, and Faecalibacterium, and increased abundance of opportunistic pathogens such as Escherichia-Shigella and Klebsiella. In contrast, probiotic-treated patients maintained a relatively balanced gut microbiota and exhibited less pronounced dysbiosis after chemotherapy. Gastrointestinal complications were also reduced following probiotic supplementation. Overall gastrointestinal toxicity was observed in 85% of control patients compared with 65% of probiotic-treated patients, while diarrhea occurred in 60% and 35%, respectively. Grade 3-4 gastrointestinal toxicity was reported in 40% of control patients compared with 20% of probiotic-treated patients. Probiotic supplementation was additionally associated with lower incidence and severity of mucositis, nausea, and vomiting. Chemotherapy responders exhibited a more favorable microbial profile with greater abundance of beneficial commensal bacteria than non-responders. Receiver operating characteristic analysis identified microbial taxa as potential predictors of chemotherapy outcomes, with AUC values of 0.81 for Bacteroides ovatus, 0.78 for Faecalibacterium prausnitzii, and 0.86 for the combined response model. The combined microbial model achieved an AUC of 0.88 for predicting severe gastrointestinal toxicity.

Overall, probiotic supplementation may help preserve intestinal microbial homeostasis, reduce chemotherapy-associated gastrointestinal toxicity, and support improved treatment outcomes in cancer patients.