Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing

We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a...
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Gespeichert in:

Autor*in:	Axel Künstner [verfasserIn] Paul Schilf [verfasserIn] Hauke Busch [verfasserIn] Saleh M. Ibrahim [verfasserIn] Misa Hirose [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 3, p 1056
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:3, p 1056

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms23031056

Katalog-ID:	DOAJ072983442

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520			\|a We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.
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allfields	10.3390/ijms23031056 doi (DE-627)DOAJ072983442 (DE-599)DOAJ024f21b64cc646f49a81aba55b75cad9 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Axel Künstner verfasserin aut Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants. mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism Biology (General) Chemistry Paul Schilf verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 3, p 1056 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:3, p 1056 https://doi.org/10.3390/ijms23031056 kostenfrei https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 kostenfrei https://www.mdpi.com/1422-0067/23/3/1056 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 3, p 1056
spelling	10.3390/ijms23031056 doi (DE-627)DOAJ072983442 (DE-599)DOAJ024f21b64cc646f49a81aba55b75cad9 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Axel Künstner verfasserin aut Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants. mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism Biology (General) Chemistry Paul Schilf verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 3, p 1056 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:3, p 1056 https://doi.org/10.3390/ijms23031056 kostenfrei https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 kostenfrei https://www.mdpi.com/1422-0067/23/3/1056 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 3, p 1056
allfields_unstemmed	10.3390/ijms23031056 doi (DE-627)DOAJ072983442 (DE-599)DOAJ024f21b64cc646f49a81aba55b75cad9 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Axel Künstner verfasserin aut Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants. mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism Biology (General) Chemistry Paul Schilf verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 3, p 1056 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:3, p 1056 https://doi.org/10.3390/ijms23031056 kostenfrei https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 kostenfrei https://www.mdpi.com/1422-0067/23/3/1056 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 3, p 1056
allfieldsGer	10.3390/ijms23031056 doi (DE-627)DOAJ072983442 (DE-599)DOAJ024f21b64cc646f49a81aba55b75cad9 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Axel Künstner verfasserin aut Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants. mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism Biology (General) Chemistry Paul Schilf verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 3, p 1056 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:3, p 1056 https://doi.org/10.3390/ijms23031056 kostenfrei https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 kostenfrei https://www.mdpi.com/1422-0067/23/3/1056 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 3, p 1056
allfieldsSound	10.3390/ijms23031056 doi (DE-627)DOAJ072983442 (DE-599)DOAJ024f21b64cc646f49a81aba55b75cad9 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Axel Künstner verfasserin aut Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants. mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism Biology (General) Chemistry Paul Schilf verfasserin aut Hauke Busch verfasserin aut Saleh M. Ibrahim verfasserin aut Misa Hirose verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 3, p 1056 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:3, p 1056 https://doi.org/10.3390/ijms23031056 kostenfrei https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 kostenfrei https://www.mdpi.com/1422-0067/23/3/1056 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 3, p 1056
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callnumber-first	Q - Science
author	Axel Künstner
spellingShingle	Axel Künstner misc QH301-705.5 misc QD1-999 misc mitochondrial DNA polymorphisms misc natural variants misc gut microbiota misc complex I misc proteobacteria misc glucose metabolism misc Biology (General) misc Chemistry Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing
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topic_title	QH301-705.5 QD1-999 Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing mitochondrial DNA polymorphisms natural variants gut microbiota complex I proteobacteria glucose metabolism
topic	misc QH301-705.5 misc QD1-999 misc mitochondrial DNA polymorphisms misc natural variants misc gut microbiota misc complex I misc proteobacteria misc glucose metabolism misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc mitochondrial DNA polymorphisms misc natural variants misc gut microbiota misc complex I misc proteobacteria misc glucose metabolism misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc mitochondrial DNA polymorphisms misc natural variants misc gut microbiota misc complex I misc proteobacteria misc glucose metabolism misc Biology (General) misc Chemistry
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title	Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing
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title_full	Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing
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title_sort	changes of gut microbiota by natural mtdna variant differences augment susceptibility to metabolic disease and ageing
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title_auth	Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing
abstract	We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.
abstractGer	We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.
abstract_unstemmed	We recently reported on two mouse strains carrying different single nucleotide variations in the mitochondrial complex I gene, i.e., B6-mt<sup<BPL</sup< mice carrying m.11902T<C and B6-mt<sup<ALR</sup< carrying m.4738C<A. B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.
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title_short	Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing
url	https://doi.org/10.3390/ijms23031056 https://doaj.org/article/024f21b64cc646f49a81aba55b75cad9 https://www.mdpi.com/1422-0067/23/3/1056 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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B6-mt<sup<BPL</sup< mice exhibited a longer lifespan and a lower metabolic disease susceptibility despite mild mitochondrial functional differences in steady-state. As natural polymorphisms in the mitochondrial DNA (mtDNA) are known to be associated with distinct patterns of gut microbial composition, we further investigated the gut microbiota composition in these mice strains. In line with mouse phenotypes, we found a significantly lower abundance of <i<Proteobacteria</i<, which is positively associated with pathological conditions, in B6-mt<sup<BPL</sup< compared to B6-mt<sup<ALR</sup< mice. A prediction of functional profile of significantly differential bacterial genera between these strains revealed an involvement of glucose metabolism pathways. Whole transcriptome analysis of liver samples from B6-mt<sup<BPL</sup< and B6-mt<sup<ALR</sup< mice confirmed these findings. Thus, both host gene expression and gut microbial changes caused by the mtDNA variant differences may contribute to the ageing and metabolic phenotypes observed in these mice strains. Since gut microbiota are easier to modulate, compared with mtDNA variants, identification of such mtDNA variants, specific gut bacterial species and bacterial metabolites may be a potential intervention to modulate common diseases, which are differentially susceptible to individuals with different mtDNA variants.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondrial DNA polymorphisms</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">natural variants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">gut microbiota</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">complex I</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">proteobacteria</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">glucose metabolism</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Chemistry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Paul Schilf</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hauke Busch</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Saleh M. 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Changes of Gut Microbiota by Natural mtDNA Variant Differences Augment Susceptibility to Metabolic Disease and Ageing

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