Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway
Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest‐derived cell (ENCC) transplantation is a potential therapeutic strategy; however...
Gespeichert in:
| Veröffentlicht in: | The EMBO journal 2023-01, Vol.42 (1), p.e111139-n/a |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext bestellen |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 1 |
| container_start_page | e111139 |
| container_title | The EMBO journal |
| container_volume | 42 |
| creator | Tian, Donghao Xu, Wenyao Pan, Weikang Zheng, Baijun Yang, Weili Jia, Wanying Liu, Yong Garstka, Malgorzata A Gao, Ya Yu, Hui |
| description | Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest‐derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype
in vitro
and
in vivo
. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short‐chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of
Bacteroides
and
Clostridium
, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome‐wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA‐mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short‐chain fatty acid metabolism‐induced MEK1/2 signaling.
Synopsis
Fecal microbiota transplantation synergy with enteric neural crest‐derived cell transplantation is tested in a rat model of hypoganglianosis to provide a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.
The intestinal microenvironment in a rat model of hypoganglionosis negatively influences enteric neural crest‐derived cell (ENCC) proliferation and migration
Fecal microbiota transplantation (FMT) relieves hypoganglionosis symptoms and promotes ENCC transplantation in vitro and vivo.
Some genera, particularly
Bacteroides
and
Clostridium
, increased after FMT, which coincided with short‐chain fatty acid (SCFA) production.
SCFA exposure stimulated ENCC proliferation, migration, and supported ENCC transplantation in the treatment of hypoganglionosis via the MEK1/2 signaling pathway.
Graphical Abstract
Fecal microbiota transplantation enhances enteric neural crest‐derived cell transplantation in a rat model of hypoganglionosis supporting a non‐surgical treatment option of neurocristopathies including Hirschsprung disease. |
| doi_str_mv | 10.15252/embj.2022111139 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_C6C</sourceid><recordid>TN_cdi_proquest_miscellaneous_2737118187</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2760461580</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4649-3d87521289dc3bd484847704f1606afa40acb766d7af857ae2026bc4d3872dc33</originalsourceid><addsrcrecordid>eNqFkTFv1DAcxS1ERY_CzoQssbCktR3H9kks7emOQlsxAHP0T-zkfErsYCeqsjHwAfiMfBJ8vUIFEsIevPze0_N7CL2g5JQWrGBnpq92p4wwRtPJl4_QgnJBMkZk8RgtCBM041Qtj9HTGHeEkEJJ-gQd5yJXTFK6QN82poYO97YOvrJ-BDwGcHHowI0wWu-wcVtwtYm4Nl2Hx60JMMzYOgw4wIh7r02HfYO38-BbcG2XRD7aiKsZf1xtzn98_W6dnmqj8c36ip4xHG3roLOuxQOM21uYn6GjBrpont-_J-jzZv1pdZldf3j7bnV-ndVc8GWWayULRpla6jqvNFfpSkl4QwUR0AAnUFdSCC2hUYUEk4oRVc11riRLkvwEvT74DsF_mUwcy97G_bfAGT_Fksk8laKokgl99Re681NIsfeUIFzQQpFEkQOV2osxmKYcgu0hzCUl5d1C5X6h8mGhJHl5bzxVvdG_Bb8mScCbA3BrOzP_17Bc31y8_8OfHuQxKV1rwkPwf2b6CRUKrnI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2760461580</pqid></control><display><type>article</type><title>Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway</title><source>Springer Nature OA Free Journals</source><creator>Tian, Donghao ; Xu, Wenyao ; Pan, Weikang ; Zheng, Baijun ; Yang, Weili ; Jia, Wanying ; Liu, Yong ; Garstka, Malgorzata A ; Gao, Ya ; Yu, Hui</creator><creatorcontrib>Tian, Donghao ; Xu, Wenyao ; Pan, Weikang ; Zheng, Baijun ; Yang, Weili ; Jia, Wanying ; Liu, Yong ; Garstka, Malgorzata A ; Gao, Ya ; Yu, Hui</creatorcontrib><description>Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest‐derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype
in vitro
and
in vivo
. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short‐chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of
Bacteroides
and
Clostridium
, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome‐wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA‐mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short‐chain fatty acid metabolism‐induced MEK1/2 signaling.
Synopsis
Fecal microbiota transplantation synergy with enteric neural crest‐derived cell transplantation is tested in a rat model of hypoganglianosis to provide a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.
The intestinal microenvironment in a rat model of hypoganglionosis negatively influences enteric neural crest‐derived cell (ENCC) proliferation and migration
Fecal microbiota transplantation (FMT) relieves hypoganglionosis symptoms and promotes ENCC transplantation in vitro and vivo.
Some genera, particularly
Bacteroides
and
Clostridium
, increased after FMT, which coincided with short‐chain fatty acid (SCFA) production.
SCFA exposure stimulated ENCC proliferation, migration, and supported ENCC transplantation in the treatment of hypoganglionosis via the MEK1/2 signaling pathway.
Graphical Abstract
Fecal microbiota transplantation enhances enteric neural crest‐derived cell transplantation in a rat model of hypoganglionosis supporting a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.15252/embj.2022111139</identifier><identifier>PMID: 36382711</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Bacteroides ; Cell therapy ; Cell- and Tissue-Based Therapy ; Clostridium ; Dysbacteriosis ; EMBO12 ; EMBO24 ; EMBO34 ; enteric neural crest‐derived cells ; Fatty acids ; Fatty Acids, Volatile - metabolism ; Fecal Microbiota Transplantation ; Fecal microflora ; fecal transplantation ; Feces ; Gene sequencing ; Hirschsprung disease ; Hirschsprung Disease - genetics ; Hirschsprung Disease - metabolism ; Hirschsprung Disease - therapy ; Hirschsprung's disease ; Innervation ; Intestine ; Kinases ; Large intestine ; Life Sciences ; MAP kinase ; Mass spectrometry ; Mass spectroscopy ; Microbiota ; Microenvironments ; Microorganisms ; Neural crest ; Phenotypes ; Rats ; rRNA 16S ; short‐chain fatty acids ; Signal Transduction ; Signaling ; Signs and symptoms ; Transcriptomes ; Transplantation</subject><ispartof>The EMBO journal, 2023-01, Vol.42 (1), p.e111139-n/a</ispartof><rights>The Author(s) 2022</rights><rights>2022 The Authors.</rights><rights>2023 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4649-3d87521289dc3bd484847704f1606afa40acb766d7af857ae2026bc4d3872dc33</citedby><cites>FETCH-LOGICAL-c4649-3d87521289dc3bd484847704f1606afa40acb766d7af857ae2026bc4d3872dc33</cites><orcidid>0000-0002-4617-7640 ; 0000-0003-2896-7275 ; 0000-0002-1886-6123 ; 0000-0002-6729-6374</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.15252/embj.2022111139$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://doi.org/10.15252/embj.2022111139$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.15252/embj.2022111139$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36382711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Donghao</creatorcontrib><creatorcontrib>Xu, Wenyao</creatorcontrib><creatorcontrib>Pan, Weikang</creatorcontrib><creatorcontrib>Zheng, Baijun</creatorcontrib><creatorcontrib>Yang, Weili</creatorcontrib><creatorcontrib>Jia, Wanying</creatorcontrib><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Garstka, Malgorzata A</creatorcontrib><creatorcontrib>Gao, Ya</creatorcontrib><creatorcontrib>Yu, Hui</creatorcontrib><title>Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest‐derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype
in vitro
and
in vivo
. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short‐chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of
Bacteroides
and
Clostridium
, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome‐wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA‐mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short‐chain fatty acid metabolism‐induced MEK1/2 signaling.
Synopsis
Fecal microbiota transplantation synergy with enteric neural crest‐derived cell transplantation is tested in a rat model of hypoganglianosis to provide a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.
The intestinal microenvironment in a rat model of hypoganglionosis negatively influences enteric neural crest‐derived cell (ENCC) proliferation and migration
Fecal microbiota transplantation (FMT) relieves hypoganglionosis symptoms and promotes ENCC transplantation in vitro and vivo.
Some genera, particularly
Bacteroides
and
Clostridium
, increased after FMT, which coincided with short‐chain fatty acid (SCFA) production.
SCFA exposure stimulated ENCC proliferation, migration, and supported ENCC transplantation in the treatment of hypoganglionosis via the MEK1/2 signaling pathway.
Graphical Abstract
Fecal microbiota transplantation enhances enteric neural crest‐derived cell transplantation in a rat model of hypoganglionosis supporting a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.</description><subject>Animals</subject><subject>Bacteroides</subject><subject>Cell therapy</subject><subject>Cell- and Tissue-Based Therapy</subject><subject>Clostridium</subject><subject>Dysbacteriosis</subject><subject>EMBO12</subject><subject>EMBO24</subject><subject>EMBO34</subject><subject>enteric neural crest‐derived cells</subject><subject>Fatty acids</subject><subject>Fatty Acids, Volatile - metabolism</subject><subject>Fecal Microbiota Transplantation</subject><subject>Fecal microflora</subject><subject>fecal transplantation</subject><subject>Feces</subject><subject>Gene sequencing</subject><subject>Hirschsprung disease</subject><subject>Hirschsprung Disease - genetics</subject><subject>Hirschsprung Disease - metabolism</subject><subject>Hirschsprung Disease - therapy</subject><subject>Hirschsprung's disease</subject><subject>Innervation</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Large intestine</subject><subject>Life Sciences</subject><subject>MAP kinase</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Microbiota</subject><subject>Microenvironments</subject><subject>Microorganisms</subject><subject>Neural crest</subject><subject>Phenotypes</subject><subject>Rats</subject><subject>rRNA 16S</subject><subject>short‐chain fatty acids</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Signs and symptoms</subject><subject>Transcriptomes</subject><subject>Transplantation</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTFv1DAcxS1ERY_CzoQssbCktR3H9kks7emOQlsxAHP0T-zkfErsYCeqsjHwAfiMfBJ8vUIFEsIevPze0_N7CL2g5JQWrGBnpq92p4wwRtPJl4_QgnJBMkZk8RgtCBM041Qtj9HTGHeEkEJJ-gQd5yJXTFK6QN82poYO97YOvrJ-BDwGcHHowI0wWu-wcVtwtYm4Nl2Hx60JMMzYOgw4wIh7r02HfYO38-BbcG2XRD7aiKsZf1xtzn98_W6dnmqj8c36ip4xHG3roLOuxQOM21uYn6GjBrpont-_J-jzZv1pdZldf3j7bnV-ndVc8GWWayULRpla6jqvNFfpSkl4QwUR0AAnUFdSCC2hUYUEk4oRVc11riRLkvwEvT74DsF_mUwcy97G_bfAGT_Fksk8laKokgl99Re681NIsfeUIFzQQpFEkQOV2osxmKYcgu0hzCUl5d1C5X6h8mGhJHl5bzxVvdG_Bb8mScCbA3BrOzP_17Bc31y8_8OfHuQxKV1rwkPwf2b6CRUKrnI</recordid><startdate>20230104</startdate><enddate>20230104</enddate><creator>Tian, Donghao</creator><creator>Xu, Wenyao</creator><creator>Pan, Weikang</creator><creator>Zheng, Baijun</creator><creator>Yang, Weili</creator><creator>Jia, Wanying</creator><creator>Liu, Yong</creator><creator>Garstka, Malgorzata A</creator><creator>Gao, Ya</creator><creator>Yu, Hui</creator><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4617-7640</orcidid><orcidid>https://orcid.org/0000-0003-2896-7275</orcidid><orcidid>https://orcid.org/0000-0002-1886-6123</orcidid><orcidid>https://orcid.org/0000-0002-6729-6374</orcidid></search><sort><creationdate>20230104</creationdate><title>Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway</title><author>Tian, Donghao ; Xu, Wenyao ; Pan, Weikang ; Zheng, Baijun ; Yang, Weili ; Jia, Wanying ; Liu, Yong ; Garstka, Malgorzata A ; Gao, Ya ; Yu, Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4649-3d87521289dc3bd484847704f1606afa40acb766d7af857ae2026bc4d3872dc33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Bacteroides</topic><topic>Cell therapy</topic><topic>Cell- and Tissue-Based Therapy</topic><topic>Clostridium</topic><topic>Dysbacteriosis</topic><topic>EMBO12</topic><topic>EMBO24</topic><topic>EMBO34</topic><topic>enteric neural crest‐derived cells</topic><topic>Fatty acids</topic><topic>Fatty Acids, Volatile - metabolism</topic><topic>Fecal Microbiota Transplantation</topic><topic>Fecal microflora</topic><topic>fecal transplantation</topic><topic>Feces</topic><topic>Gene sequencing</topic><topic>Hirschsprung disease</topic><topic>Hirschsprung Disease - genetics</topic><topic>Hirschsprung Disease - metabolism</topic><topic>Hirschsprung Disease - therapy</topic><topic>Hirschsprung's disease</topic><topic>Innervation</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Large intestine</topic><topic>Life Sciences</topic><topic>MAP kinase</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Microbiota</topic><topic>Microenvironments</topic><topic>Microorganisms</topic><topic>Neural crest</topic><topic>Phenotypes</topic><topic>Rats</topic><topic>rRNA 16S</topic><topic>short‐chain fatty acids</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Signs and symptoms</topic><topic>Transcriptomes</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Donghao</creatorcontrib><creatorcontrib>Xu, Wenyao</creatorcontrib><creatorcontrib>Pan, Weikang</creatorcontrib><creatorcontrib>Zheng, Baijun</creatorcontrib><creatorcontrib>Yang, Weili</creatorcontrib><creatorcontrib>Jia, Wanying</creatorcontrib><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Garstka, Malgorzata A</creatorcontrib><creatorcontrib>Gao, Ya</creatorcontrib><creatorcontrib>Yu, Hui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Tian, Donghao</au><au>Xu, Wenyao</au><au>Pan, Weikang</au><au>Zheng, Baijun</au><au>Yang, Weili</au><au>Jia, Wanying</au><au>Liu, Yong</au><au>Garstka, Malgorzata A</au><au>Gao, Ya</au><au>Yu, Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2023-01-04</date><risdate>2023</risdate><volume>42</volume><issue>1</issue><spage>e111139</spage><epage>n/a</epage><pages>e111139-n/a</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><abstract>Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest‐derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation. We found that the hypoganglionosis intestinal microenvironment negatively influenced the ENCC functional phenotype
in vitro
and
in vivo
. Combining 16S rDNA sequencing and targeted mass spectrometry revealed microbial dysbiosis and reduced short‐chain fatty acid (SCFA) production in the hypoganglionic gut. FMT increased the abundance of
Bacteroides
and
Clostridium
, SCFA production, and improved outcomes following ENCC transplantation. SCFAs alone stimulated ENCC proliferation, migration, and supported ENCC transplantation. Transcriptome‐wide mRNA sequencing identified MAPK signaling as the top differentially regulated pathway in response to SCFA exposure, and inhibition of MEK1/2 signaling abrogated the SCFA‐mediated effects on ENCC. This study demonstrates that FMT improves cell therapy for hypoganglionosis via short‐chain fatty acid metabolism‐induced MEK1/2 signaling.
Synopsis
Fecal microbiota transplantation synergy with enteric neural crest‐derived cell transplantation is tested in a rat model of hypoganglianosis to provide a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.
The intestinal microenvironment in a rat model of hypoganglionosis negatively influences enteric neural crest‐derived cell (ENCC) proliferation and migration
Fecal microbiota transplantation (FMT) relieves hypoganglionosis symptoms and promotes ENCC transplantation in vitro and vivo.
Some genera, particularly
Bacteroides
and
Clostridium
, increased after FMT, which coincided with short‐chain fatty acid (SCFA) production.
SCFA exposure stimulated ENCC proliferation, migration, and supported ENCC transplantation in the treatment of hypoganglionosis via the MEK1/2 signaling pathway.
Graphical Abstract
Fecal microbiota transplantation enhances enteric neural crest‐derived cell transplantation in a rat model of hypoganglionosis supporting a non‐surgical treatment option of neurocristopathies including Hirschsprung disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36382711</pmid><doi>10.15252/embj.2022111139</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-4617-7640</orcidid><orcidid>https://orcid.org/0000-0003-2896-7275</orcidid><orcidid>https://orcid.org/0000-0002-1886-6123</orcidid><orcidid>https://orcid.org/0000-0002-6729-6374</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | ISSN: 0261-4189 |
| ispartof | The EMBO journal, 2023-01, Vol.42 (1), p.e111139-n/a |
| issn | 0261-4189 1460-2075 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2737118187 |
| source | Springer Nature OA Free Journals |
| subjects | Animals Bacteroides Cell therapy Cell- and Tissue-Based Therapy Clostridium Dysbacteriosis EMBO12 EMBO24 EMBO34 enteric neural crest‐derived cells Fatty acids Fatty Acids, Volatile - metabolism Fecal Microbiota Transplantation Fecal microflora fecal transplantation Feces Gene sequencing Hirschsprung disease Hirschsprung Disease - genetics Hirschsprung Disease - metabolism Hirschsprung Disease - therapy Hirschsprung's disease Innervation Intestine Kinases Large intestine Life Sciences MAP kinase Mass spectrometry Mass spectroscopy Microbiota Microenvironments Microorganisms Neural crest Phenotypes Rats rRNA 16S short‐chain fatty acids Signal Transduction Signaling Signs and symptoms Transcriptomes Transplantation |
| title | Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA‐induced MEK1/2 signaling pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T22%3A39%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_C6C&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fecal%20microbiota%20transplantation%20enhances%20cell%20therapy%20in%20a%20rat%20model%20of%20hypoganglionosis%20by%20SCFA%E2%80%90induced%20MEK1/2%20signaling%20pathway&rft.jtitle=The%20EMBO%20journal&rft.au=Tian,%20Donghao&rft.date=2023-01-04&rft.volume=42&rft.issue=1&rft.spage=e111139&rft.epage=n/a&rft.pages=e111139-n/a&rft.issn=0261-4189&rft.eissn=1460-2075&rft_id=info:doi/10.15252/embj.2022111139&rft_dat=%3Cproquest_C6C%3E2760461580%3C/proquest_C6C%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2760461580&rft_id=info:pmid/36382711&rfr_iscdi=true |