IMR Press / FBL / Volume 28 / Issue 3 / DOI: 10.31083/j.fbl2803043
Open Access Original Research
Effects of Intestinal Microorganisms on Influenza-Infected Mice with Antibiotic-Induced Intestinal Dysbiosis, through the TLR7 Signaling Pathway
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1 Department of Microbiology and Immunology, Basic Medicine College, Jinan University, 510632 Guangzhou, Guangdong, China
2 School of Chemistry & Pharmaceutical Sciences, Guangxi Normal University, 541001 Guilin, Guangxi, China
3 School of Pharmacy, Guangdong Lingnan Institute of Technology, 510663 Guangzhou, Guangdong, China
4 Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, 510632 Guangzhou, Guangdong, China
5 Department of Blood Transfusion, The Sixth Affiliated Hospital, Sun Yat-Sen University, 510632 Guangzhou, Guangdong, China
*Correspondence: chengwl@mail.sysu.edu.cn (Wenli Cheng); tjzhy@jnu.edu.cn (Zhenyou Jiang)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(3), 43; https://doi.org/10.31083/j.fbl2803043
Submitted: 14 September 2022 | Revised: 7 December 2022 | Accepted: 12 December 2022 | Published: 2 March 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Stability of intestinal flora is not only important for maintaining stable immune functions; it is also a key immune channel communicating the interaction between lung and intestine. In this study, probiotics and fecal microbiota transplantation (FMT) were used to regulate influenza-infected mice with antibiotic-induced intestinal dysbiosis and the effects of intestinal microorganisms on these mice were subsequently observed and evaluated. Methods: Mice are housed in a normal environment with intranasal infection with influenza virus (FM1). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine messenger RNA expression and lung viral replication of toll-like receptor 7 (TLR7), myeloid differentiation primary reaction 88 (MyD88) and nuclear factor κB (ss) p65 in the TLR7 signaling pathway. Western blotting is used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T regulated cells. Results: Results showed that compared with the simple virus group, both diversity and species of intestinal flora in influenza-infected mice with antibiotic-induced intestinal dysbiosis were lower, in vivo viral replication was significantly increased, lung and intestinal tissues were seriously damaged, degree of inflammation increased, expression of the TLR7 signaling pathway increased, and the Th1/Th2:Th17/Treg ratio decreased. Probiotics and FMT effectively regulated intestinal flora, improved pathological lung changes and inflammation caused by influenza infection, and adjusted the TLR7 signaling pathway and the Th1/Th2:Th17/Treg ratio. This effect was not obvious in TLR7-/- mice.In summary, by affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. Conclusions: By affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. In summary, damage to lung tissue and intestinal mucosa in influenza-infected mice with antibiotic-induced intestinal dysbiosis is more serious compared to simple virus-infected mice. Improving intestinal flora using probiotics or FMT can alleviate intestinal inflammation and improve pulmonary inflammation through the TLR7 signaling pathway.

Keywords
intestinal flora
probiotics
influenza A virus FM1 mouse lung adaptation strain
fecal microbiota transplantation
TLR7
Funding
2019A1515011071/Science and Technology Projects of Guangdong Province
82074133/National Natural Science Foundation of China
2014ZX10003002-003–002/National Science and Technology Major Infectious Diseases Project during the 12th 5-Year Plan Period
21621101/Fundamental Research Funds for the Central Universities
Figures
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