Table 1 Selection of chemotherapeutic agents and the bidirectional effects between the chemotherapy and intestinal microbiota

Cisplatin

Damages mucosal barrier by impairing DNA replication of rapidly proliferating epithelial cells [61]

Facilitates translocation of gut bacteria

Commensal gut bacteria influences genotoxicity by inducing reactive oxygen species (ROS) production and recruitment of pathogenic Th17 cells in the tumor microenvironment independently of immunity elicited by immunogenic cell death [12]

CDI [62]

Ototoxicity [63]

Antibiotics against Gram-positive bacteria abrogate antitumor chemotoxicity, increase tumor size and decrease survival rate

Cisplatin alone show better response compared to a combined treatment of cisplatin and antibiotics in mice with lung cancer [64]. The combination treatment increased tumor size and decreased survival rate

Lactobacillus acidophilus restores antitumor efficacy following antibiotic treatment [64, 65]

Restoration of gut microbiota and epithelial integrity by FMT [66] and treatment with D-methionine [67, 68] prevent infections and ototoxicity without affecting tumor chemotoxicity

Paclitaxel

Increases gut permeability, as indicated by 5-fold elevation in circulating LPS-binding protein and systemic inflammation [69]

Reduces abundance of Roseburia, Porphyromonadaceae and Akkermanisa Muciniphila [69, 70]

Chemotherapy-induced peripheral neuropathic pain (CIPN) [70]

CDI [71, 72]

FMT increases A. Muciniphila abundance and reduces CIPN [70]

5-Fluoruracil

Reduces Clostridium spp. and increases members of Proteobacteria, mainly Enterobacteriaceae [73]

Damages mucosal barrier

Mucositis along the entire gastrointestinal tract [74]

CDI [75, 76]

Oral butyrate supplementation improves gut barrier by reducing inflammation and mucositis [77]

Antibiotics reduce mucositis and cytokine production but also diminish antitumor efficacy [78] and promote chemotherapy resistance [11]

Cyclophosphamide

Triggers disruption of gut barrier by altering bacterial composition

Gram-positive bacteria such as Enterococcus hirae, Lactobacillus johnsonii, and L. murinus translocate from gut into mesenteric lymph nodes and spleen [56]. This enhances immune responses by the production of interferon gamma (IFN-γ) and activation of Th17 cells

CDI [75]

Antibiotics against Gram-positive bacteria reduce Th17 responses, and subsequent development of cyclophosphamide-resistance

Re-establishment of E. hirae alone restores antitumor activity [79].

E. hirae decreases tumor-infiltrating T_regs. Barnesiella intestinihominis accumulates in the colon and increases the number of intra-tumoral IFN-γ-producing γδT cells. E. hirae and B. intestinihominis synergistically stimulate local and systemic immunity to improve anticancer effects [79].

Nod1^−/−Nod2^−/− mice having abundant B. intestinihominis demonstrate increased γδT cells in tumor beds and enhanced cyclophosphamide efficacy [79]