Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice

Abstract Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesio...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiaoxiao Zhang, Liang Wang, Asif Iqbal Khan, Ata Ur Rehman, Kavish Hasnain Khinsar, Yi Xin
Format: Article
Language:English
Published: SpringerOpen 2025-01-01
Series:AMB Express
Subjects:
Online Access:https://doi.org/10.1186/s13568-024-01796-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832585385877700608
author Xiaoxiao Zhang
Liang Wang
Asif Iqbal Khan
Ata Ur Rehman
Kavish Hasnain Khinsar
Yi Xin
author_facet Xiaoxiao Zhang
Liang Wang
Asif Iqbal Khan
Ata Ur Rehman
Kavish Hasnain Khinsar
Yi Xin
author_sort Xiaoxiao Zhang
collection DOAJ
description Abstract Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted. In our search for new intestinal mucositis therapies, we wanted to see how Lentinan (LT), derived from Lentinus edodes, would fare in mouse models of intestinal mucositis. To create the intestinal mucositis model in mice, we gave them intra-peritoneal doses of 5-fluorouracil (5-FU) (50 mg/kg) and then tested the effects of Lentinan on intestinal mucositis. This examination required constant monitoring of several factors, such as body weight fluctuations, food consumption, and diarrhea. In addition, we measured the levels of certain inflammatory cytokines (Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-10 (IL-10), looked at the expression of tight junction proteins (Zonula Occludens-1(ZO-1), Claudin-1), measured mucin-2 levels, and looked into changes in the gut flora. In the mouse model of intestinal mucositis, our findings showed that LT effectively reduced weight loss, increased food intake, and relieved diarrhea. Concurrently, we saw a decrease in the expression of inflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as a considerable increase in the concentration of IL-10. Furthermore, LT reduced intestinal mucositis by increasing the length and structural integrity of the colon. Furthermore, increased expression of tight junction proteins (ZO-1, Claudin-1), mucin-2, and an increase in the number of goblet cells all confirmed our previous findings. Notably, the makeup of beneficial bacteria in the stomach increased as well. Finally, our findings suggest that LT can effectively prevent 5-fluorouracil-induced intestinal mucositis in mice by improving immune function, restoring intestinal barrier integrity, and rebalancing gut microbial flora.
format Article
id doaj-art-d0cfe5c105424f0f8e152bd33008a767
institution Kabale University
issn 2191-0855
language English
publishDate 2025-01-01
publisher SpringerOpen
record_format Article
series AMB Express
spelling doaj-art-d0cfe5c105424f0f8e152bd33008a7672025-01-26T12:53:55ZengSpringerOpenAMB Express2191-08552025-01-0115111510.1186/s13568-024-01796-zLentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis miceXiaoxiao Zhang0Liang Wang1Asif Iqbal Khan2Ata Ur Rehman3Kavish Hasnain Khinsar4Yi Xin5Department of Biotechnology, College of Basic Medical Science, Dalian Medical UniversityDepartment of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Biotechnology, College of Basic Medical Science, Dalian Medical UniversityDepartment of Biotechnology, College of Basic Medical Science, Dalian Medical UniversityDepartment of Meat Sciences and Animal Biologics, University of Wisconsin-MadisonDepartment of Biotechnology, College of Basic Medical Science, Dalian Medical UniversityAbstract Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted. In our search for new intestinal mucositis therapies, we wanted to see how Lentinan (LT), derived from Lentinus edodes, would fare in mouse models of intestinal mucositis. To create the intestinal mucositis model in mice, we gave them intra-peritoneal doses of 5-fluorouracil (5-FU) (50 mg/kg) and then tested the effects of Lentinan on intestinal mucositis. This examination required constant monitoring of several factors, such as body weight fluctuations, food consumption, and diarrhea. In addition, we measured the levels of certain inflammatory cytokines (Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-10 (IL-10), looked at the expression of tight junction proteins (Zonula Occludens-1(ZO-1), Claudin-1), measured mucin-2 levels, and looked into changes in the gut flora. In the mouse model of intestinal mucositis, our findings showed that LT effectively reduced weight loss, increased food intake, and relieved diarrhea. Concurrently, we saw a decrease in the expression of inflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as a considerable increase in the concentration of IL-10. Furthermore, LT reduced intestinal mucositis by increasing the length and structural integrity of the colon. Furthermore, increased expression of tight junction proteins (ZO-1, Claudin-1), mucin-2, and an increase in the number of goblet cells all confirmed our previous findings. Notably, the makeup of beneficial bacteria in the stomach increased as well. Finally, our findings suggest that LT can effectively prevent 5-fluorouracil-induced intestinal mucositis in mice by improving immune function, restoring intestinal barrier integrity, and rebalancing gut microbial flora.https://doi.org/10.1186/s13568-024-01796-z5-fluorouracilIntestinal mucositisLentinanIntestinal floraIntestinal barrier
spellingShingle Xiaoxiao Zhang
Liang Wang
Asif Iqbal Khan
Ata Ur Rehman
Kavish Hasnain Khinsar
Yi Xin
Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
AMB Express
5-fluorouracil
Intestinal mucositis
Lentinan
Intestinal flora
Intestinal barrier
title Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
title_full Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
title_fullStr Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
title_full_unstemmed Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
title_short Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice
title_sort lentinan s effect on gut microbiota and inflammatory cytokines in 5 fu induced mucositis mice
topic 5-fluorouracil
Intestinal mucositis
Lentinan
Intestinal flora
Intestinal barrier
url https://doi.org/10.1186/s13568-024-01796-z
work_keys_str_mv AT xiaoxiaozhang lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice
AT liangwang lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice
AT asifiqbalkhan lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice
AT ataurrehman lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice
AT kavishhasnainkhinsar lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice
AT yixin lentinanseffectongutmicrobiotaandinflammatorycytokinesin5fuinducedmucositismice