Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhe Zhao, Jingwen Ning, Xiu-qi Bao, Meiyu Shang, Jingwei Ma, Gen Li, Dan Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Fecal microbiota transplantation Parkinson’s disease Rotenone-induced mouse model Microbiota-gut-brain axis 16S RNA sequencing Microbial ecology QR100-130
Acceso en línea:	https://doaj.org/article/ecea8d05303449e0a45e9dce517ec48f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ecea8d05303449e0a45e9dce517ec48f
record_format	dspace
spelling	oai:doaj.org-article:ecea8d05303449e0a45e9dce517ec48f2021-11-21T12:06:42ZFecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis10.1186/s40168-021-01107-92049-2618https://doaj.org/article/ecea8d05303449e0a45e9dce517ec48f2021-11-01T00:00:00Zhttps://doi.org/10.1186/s40168-021-01107-9https://doaj.org/toc/2049-2618Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstractZhe ZhaoJingwen NingXiu-qi BaoMeiyu ShangJingwei MaGen LiDan ZhangBMCarticleFecal microbiota transplantationParkinson’s diseaseRotenone-induced mouse modelMicrobiota-gut-brain axis16S RNA sequencingMicrobial ecologyQR100-130ENMicrobiome, Vol 9, Iss 1, Pp 1-27 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fecal microbiota transplantation Parkinson’s disease Rotenone-induced mouse model Microbiota-gut-brain axis 16S RNA sequencing Microbial ecology QR100-130
spellingShingle	Fecal microbiota transplantation Parkinson’s disease Rotenone-induced mouse model Microbiota-gut-brain axis 16S RNA sequencing Microbial ecology QR100-130 Zhe Zhao Jingwen Ning Xiu-qi Bao Meiyu Shang Jingwei Ma Gen Li Dan Zhang Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
description	Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstract
format	article
author	Zhe Zhao Jingwen Ning Xiu-qi Bao Meiyu Shang Jingwei Ma Gen Li Dan Zhang
author_facet	Zhe Zhao Jingwen Ning Xiu-qi Bao Meiyu Shang Jingwei Ma Gen Li Dan Zhang
author_sort	Zhe Zhao
title	Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
title_short	Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
title_full	Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
title_fullStr	Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
title_full_unstemmed	Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis
title_sort	fecal microbiota transplantation protects rotenone-induced parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-tlr4 signaling pathway through the microbiota-gut-brain axis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ecea8d05303449e0a45e9dce517ec48f
work_keys_str_mv	AT zhezhao fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT jingwenning fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT xiuqibao fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT meiyushang fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT jingweima fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT genli fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis AT danzhang fecalmicrobiotatransplantationprotectsrotenoneinducedparkinsonsdiseasemiceviasuppressinginflammationmediatedbythelipopolysaccharidetlr4signalingpathwaythroughthemicrobiotagutbrainaxis
_version_	1718419279554019328

Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Ejemplares similares