Cargando…

Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model

The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in m...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Wei, Zhang, Di, He, Tian, Liu, Yingying, Shao, Limei, Lv, Zhongping, Pu, Xiaoping, Wang, Yufang, Liu, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040537/
https://www.ncbi.nlm.nih.gov/pubmed/36992690
http://dx.doi.org/10.3389/fcimb.2023.1130820
_version_ 1784912494388576256
author Lv, Wei
Zhang, Di
He, Tian
Liu, Yingying
Shao, Limei
Lv, Zhongping
Pu, Xiaoping
Wang, Yufang
Liu, Ling
author_facet Lv, Wei
Zhang, Di
He, Tian
Liu, Yingying
Shao, Limei
Lv, Zhongping
Pu, Xiaoping
Wang, Yufang
Liu, Ling
author_sort Lv, Wei
collection PubMed
description The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 (Lacto)-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients.
format Online
Article
Text
id pubmed-10040537
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-100405372023-03-28 Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model Lv, Wei Zhang, Di He, Tian Liu, Yingying Shao, Limei Lv, Zhongping Pu, Xiaoping Wang, Yufang Liu, Ling Front Cell Infect Microbiol Cellular and Infection Microbiology The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 (Lacto)-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients. Frontiers Media S.A. 2023-03-13 /pmc/articles/PMC10040537/ /pubmed/36992690 http://dx.doi.org/10.3389/fcimb.2023.1130820 Text en Copyright © 2023 Lv, Zhang, He, Liu, Shao, Lv, Pu, Wang and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Lv, Wei
Zhang, Di
He, Tian
Liu, Yingying
Shao, Limei
Lv, Zhongping
Pu, Xiaoping
Wang, Yufang
Liu, Ling
Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title_full Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title_fullStr Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title_full_unstemmed Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title_short Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
title_sort combination of lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10040537/
https://www.ncbi.nlm.nih.gov/pubmed/36992690
http://dx.doi.org/10.3389/fcimb.2023.1130820
work_keys_str_mv AT lvwei combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT zhangdi combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT hetian combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT liuyingying combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT shaolimei combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT lvzhongping combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT puxiaoping combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT wangyufang combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel
AT liuling combinationoflactobacillusplantarumimprovestheeffectsoftacrolimusoncolitisinamousemodel