Table 3 Clinical studies deciphering the predictive value of the gut microbiota in radiation-induced toxicities

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