title: Susceptibility of lactic acid bacteria, bifidobacteria and other bacteria of intestinal origin to chemotherapeutic agents.
abstract: 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.
authors: Departamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Paseo Río Linares s/n, Asturias, Villaviciosa 33300, Spain. Electronic address: abflorez@ipla.csic.es.
authors: Ana B
authors: AB
authors: Flórez
authors: Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Celestino Villamil s/n, Asturias, Oviedo 33006, Spain.
authors: Marta
authors: M
authors: Sierra
authors: Departamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Paseo Río Linares s/n, Asturias, Villaviciosa 33300, Spain.
authors: Patricia
authors: P
authors: Ruas-Madiedo
authors: Departamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Paseo Río Linares s/n, Asturias, Villaviciosa 33300, Spain.
authors: Baltasar
authors: B
authors: Mayo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001644:Bifidobacterium / Q000187:drug effects* / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome; D006801:Humans; D056546:Lactobacillales / Q000187:drug effects* / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D064307:Microbiota
chemical_list: D000970:Antineoplastic Agents
keywords: Bifidobacteria; Chemotherapy; Lactic acid bacteria; Minimum inhibitory concentration; Mucositis; Susceptibility testing