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23-09-2022 | Antibiotic | Original Article

Long-term use of broad-spectrum antibiotics affects Ly6C^hi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy

Authors: Yanhong Wu, Xiaolei Tang, Feng Hu, Tao Zhu, Hui Liu, Yanjing Xiong, Xiaoxuan Zuo, Aiping Xu, Xiufen Zhuang

Published in: Immunologic Research | Issue 6/2022

Abstract

The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A⁺ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6C^hi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.

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Title: Long-term use of broad-spectrum antibiotics affects Ly6Chi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy
Authors: Yanhong Wu
Xiaolei Tang
Feng Hu
Tao Zhu
Hui Liu
Yanjing Xiong
Xiaoxuan Zuo
Aiping Xu
Xiufen Zhuang
Publication date: 23-09-2022
Publisher: Springer US
Keywords: Antibiotic
Respiratory Microbiota
Cytostatic Therapy
Published in: Immunologic Research / Issue 6/2022
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-022-09313-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Long-term use of broad-spectrum antibiotics affects Ly6C^hi monocyte recruitment and IL-17A and IL-22 production through the gut microbiota in tumor-bearing mice treated with chemotherapy

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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