AUTHOR=Zhao Xuanqi , Wu Heng , Zhu Ruizhe , Shang Gaishuang , Wei Jing , Shang Haitao , Tian Puyuan , Chen Tingtao , Wei Hong 

TITLE=Combination of thalidomide and Clostridium butyricum relieves chemotherapy-induced nausea and vomiting via gut microbiota and vagus nerve activity modulation

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1220165

DOI=10.3389/fimmu.2023.1220165

ISSN=1664-3224

ABSTRACT=<p>Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and <italic>Clostridium butyricum</italic>. Our results suggested that the combination of THD and <italic>C. butyricum</italic> abundantly enhanced the anticancer effect of cisplatin <italic>via</italic> activating the caspase-3 apoptosis pathway, and also ameliorated CINV <italic>via</italic> inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HT<sub>3</sub>R and NK-1R) in brain and colon. Additionally, the combination of THD and <italic>C. butyricum</italic> reversed the gut dysbacteriosis in CRC mice by increasing the abundance of <italic>Clostridium</italic>, <italic>Lactobacillus</italic>, <italic>Bifidobacterium</italic>, and <italic>Ruminococcus</italic> at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1β, and TNF-α. In all, these results suggest that the combination of THD and <italic>C. butyricum</italic> had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.</p>