Susceptibility of lactic acid bacteria, bifidobacteria and other bacteria of intestinal origin to chemotherapeutic agents

- Lactic acid bacteria (LAB) and bifidobacteria showed variable resistance to tested chemotherapeutic agents (CAs).
- Greatest interspecies variation in MICs was observed for CAs pemetrexed and afatinib.
- Intestinal bacteria other than LAB and bifidobacteria proved to be highly resistant to all CAs.

Chemotherapy is a cornerstone of cancer treatment but it can have serious side effects, such as intestinal mucositis. This work reports the susceptibility/resistance profiles of 34 species of lactic acid bacteria (LAB), bifidobacteria and other intestinal bacteria from different collections to various chemotherapeutic agents (CAs) currently used in cancer treatments in an attempt to identify microorganisms that could prevent or treat mucositis symptoms. The highest concentrations of the CAs tested were equal to or higher than those reached in plasma during anticancer treatments. All 34 species proved to be resistant at the highest concentrations assayed [minimum inhibitory concentrations (MICs) > 128 µg/mL] to capecitabine, cyclophosphamide, docetaxel, erlotinib, gefitinib, irinotecan and paclitaxel. For doxorubicin, 5-fluorouracil, gemcitabine and, especially, afatinib and pemetrexed, interspecies variation in the MIC was observed. In further work to assess the interspecies and intraspecies variability, MICs of the CAs pemetrexed and afatinib were determined for 32 strains belonging to four Bifidobacterium spp. of intestinal origin. For pemetrexed, a bimodal MIC curve was obtained (modes <2-8 µg/mL and >256 µg/mL), whilst a normal unimodal curve was obtained for afatinib (mode 128 µg/mL). Altogether, these results suggest that the majority of CAs should not, by themselves, perturb the microbial populations of the gut microbiota (but considering that they could be transformed in vivo into more toxic compounds). However, LAB and bifidobacteria, which are key players in the intestinal microbial balance of the healthy state, might be particularly inhibited by CAs such as gemcitabine or doxorubicin.