Table 3.
Clinical studies deciphering the predictive value of the gut microbiota in radiation-induced toxicities
| References | Study population | Major techniques | Endpoints | Highlights and Comments |
|---|---|---|---|---|
| Manichanh, Spain, [29] | Gynecological (n = 6) or rectal cancer (n = 4) patients | Feaces for 16S rRNA DGGE + 16S rRNA sequencing | ARE (CTCAE) | The first study using 16S rRNA analysis in clinical cohorts to reveal: a) microbiota perturbations in patients with diarrhea is more drastic throughout radiotherapy; b) baseline microbiota features are distinguishable between diarrhea vs. no-diarrhea |
| Wang, China, [28] | Cervical (n = 8), colorectal (n = 2) and anal (n = 1) cancer patients | Feaces for 16S rRNA sequencing + blood for inflammatory markers assay | ARE (CTCAE) | The first study describing pre-treatment microbiota features predictive of acute diarrhea, including lower SDI and higher Firmicute/Bacteroides ratio |
| Wang, China, [30] | Stage II-IV cervical cancer patients (n = 18) | Feaces for 16S rRNA sequencing + coculture of colonic epithelium with faecal bacteria + blood for inflammatory marker assay | ARE (RTOG) | Baseline Coprococcus is enriched and microbial diversity is declined (including SDI) in patients predisposing to ARE; coculture assay demonstrated that dysbiotic microbiota from patients with severe ARE induces barrier impairment and pro-inflammatory response |
| Colbert, US, [31] | Stage I-IV cervical cancer patients (n = 35) | Feaces for 16S rRNA sequencing | ARE (bowel part of EPIC questionnaire, patient-reported) | High SDI independently predicts better near-term gastrointestinal function; Clostridiales is enriched in milder ARE and Sutterella in severe ARE patients |
| Colbert, US, [32] | Cervical, vaginal and anal cancer patients (n = 59) | Rectal swabs for 16S rRNA sequencing | CRE (RTOG and CTCAE) | Baseline Sutterella is underrepresented in CRE patients |
| Cai, China, [33] | Stage I-III cervical (n = 16) and endometrial (n = 1) cancer patients | Feaces for 16S rRNA sequencing + LC–MS | ARE (RTOG) | The first integrative multi-omics translational study constructing prediction model for ARE, using abundances of Erysipelatoclostridium and its downstream metabolite, ptilosteroid A |
| Ferreira, UK, [34] | Prostate cancer, early cohort (n = 32); late cohort (n = 87); coloscopy cohort (n = 15) | Feaces for 16S rRNA sequencing | ARE; CRE (clinician-reported: RTOG, LENT/SOM, UCLA-PCI outcomes; patient-reported: modified QoL questionnaire) | The first study reporting how gut microbiota affects CRE and emphasizing on SCFA metabolism by integration with inferred metagenomic analysis. Non-significant trend towards higher Sutterella exists in acute symptomatic patients |
| Ferreira, UK, [45] | Prostate cancer patients (n = 32) | Feaces, urine and plasma for NMR + LC–MS | CRE (patient-reported: modified QoL questionnaire) | The first study reporting microbiota-related metabolite profile associated with CRE, reinforcing the significance of SCFA in toxicity amelioration |
| Zhang, China, [35] | Stage I-III rectal cancer patients (n = 22) | Feaces for 16S rRNA sequencing | ARE (CTCAE) | Clostridia, Bifidobacterium and primary bile acid biosynthesis pathway are enriched in low toxicity patients |
| Zhang, China, [36] | Stage I-III rectal cancer patients (n = 84) | Feaces for 16S rRNA sequencing | ARE; myelosuppression (both per CTCAE) | The first study on both myelosuppression and ARE and accordingly constructing two robust prediction models. Baseline Akkermansia, Bifidobacterium and Coprococcus are enriched in low toxicity patients whereas β-glucuronidase-producing and pro-diarrhea Escherichia enriched in high toxicity patients |
| Colbert, US, [37] | Stage I-IV anal squamous cell cancer patients (n = 22) | Anorectal swabs at tumor site for 16S rRNA sequencing | ARE (bowel part of EPIC questionnaire); acute anal dermatitis (CTCAE) | The first pilot study focusing on both ARE and anal dermatitis |
DGGE Denaturing gradient gel electrophoresis, ARE Acute radiation enteropathy, CTCAE Common terminology for adverse events, SDI Shannon diversity index, RTOG Radiation therapy oncology group scale, EPIC Expanded prostate cancer index composite, CRE Chronic radiation enteropathy, LENT/SOM Late effects of normal tissues scale, UCLA-PCI = Bowel problem/distress measured with the university of California, Los Angeles prostate cancer index, QoL = Quality of life, SCFA Short chain fatty acid; NMR Nuclear magnetic resonance, LC–MS Liquid chromatography-mass spectrometry