Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model

Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body....
Ausführliche Beschreibung

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Autor*in:	Kim, Namkwon [verfasserIn] Ju, In Gyoung Jeon, Seung Ho Lee, Yeongae Jung, Min-Ji Gee, Min Sung Cho, Jae Seok Inn, Kyung-Soo Garrett-Sinha, Lee Ann Oh, Myung Sook Lee, Jong Kil

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Alzheimer’s disease Microbiota-Gut-Brain axis Microfold cells Microglia

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Journal of neuroinflammation - London : BioMed Central, 2004, 20(2023), 1 vom: 27. Nov.
Übergeordnetes Werk:	volume:20 ; year:2023 ; number:1 ; day:27 ; month:11

Links:	Volltext

DOI / URN:	10.1186/s12974-023-02966-9

Katalog-ID:	SPR053880862

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520			\|a Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.
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allfields	10.1186/s12974-023-02966-9 doi (DE-627)SPR053880862 (SPR)s12974-023-02966-9-e DE-627 ger DE-627 rakwb eng Kim, Namkwon verfasserin aut Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Ju, In Gyoung aut Jeon, Seung Ho aut Lee, Yeongae aut Jung, Min-Ji aut Gee, Min Sung aut Cho, Jae Seok aut Inn, Kyung-Soo aut Garrett-Sinha, Lee Ann aut Oh, Myung Sook aut Lee, Jong Kil aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 27. Nov. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:27 month:11 https://dx.doi.org/10.1186/s12974-023-02966-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 20 2023 1 27 11
spelling	10.1186/s12974-023-02966-9 doi (DE-627)SPR053880862 (SPR)s12974-023-02966-9-e DE-627 ger DE-627 rakwb eng Kim, Namkwon verfasserin aut Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Ju, In Gyoung aut Jeon, Seung Ho aut Lee, Yeongae aut Jung, Min-Ji aut Gee, Min Sung aut Cho, Jae Seok aut Inn, Kyung-Soo aut Garrett-Sinha, Lee Ann aut Oh, Myung Sook aut Lee, Jong Kil aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 27. Nov. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:27 month:11 https://dx.doi.org/10.1186/s12974-023-02966-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 20 2023 1 27 11
allfields_unstemmed	10.1186/s12974-023-02966-9 doi (DE-627)SPR053880862 (SPR)s12974-023-02966-9-e DE-627 ger DE-627 rakwb eng Kim, Namkwon verfasserin aut Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Ju, In Gyoung aut Jeon, Seung Ho aut Lee, Yeongae aut Jung, Min-Ji aut Gee, Min Sung aut Cho, Jae Seok aut Inn, Kyung-Soo aut Garrett-Sinha, Lee Ann aut Oh, Myung Sook aut Lee, Jong Kil aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 27. Nov. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:27 month:11 https://dx.doi.org/10.1186/s12974-023-02966-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 20 2023 1 27 11
allfieldsGer	10.1186/s12974-023-02966-9 doi (DE-627)SPR053880862 (SPR)s12974-023-02966-9-e DE-627 ger DE-627 rakwb eng Kim, Namkwon verfasserin aut Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Ju, In Gyoung aut Jeon, Seung Ho aut Lee, Yeongae aut Jung, Min-Ji aut Gee, Min Sung aut Cho, Jae Seok aut Inn, Kyung-Soo aut Garrett-Sinha, Lee Ann aut Oh, Myung Sook aut Lee, Jong Kil aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 27. Nov. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:27 month:11 https://dx.doi.org/10.1186/s12974-023-02966-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 20 2023 1 27 11
allfieldsSound	10.1186/s12974-023-02966-9 doi (DE-627)SPR053880862 (SPR)s12974-023-02966-9-e DE-627 ger DE-627 rakwb eng Kim, Namkwon verfasserin aut Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213 Ju, In Gyoung aut Jeon, Seung Ho aut Lee, Yeongae aut Jung, Min-Ji aut Gee, Min Sung aut Cho, Jae Seok aut Inn, Kyung-Soo aut Garrett-Sinha, Lee Ann aut Oh, Myung Sook aut Lee, Jong Kil aut Enthalten in Journal of neuroinflammation London : BioMed Central, 2004 20(2023), 1 vom: 27. Nov. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:20 year:2023 number:1 day:27 month:11 https://dx.doi.org/10.1186/s12974-023-02966-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_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 20 2023 1 27 11
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authorswithroles_txt_mv	Kim, Namkwon @@aut@@ Ju, In Gyoung @@aut@@ Jeon, Seung Ho @@aut@@ Lee, Yeongae @@aut@@ Jung, Min-Ji @@aut@@ Gee, Min Sung @@aut@@ Cho, Jae Seok @@aut@@ Inn, Kyung-Soo @@aut@@ Garrett-Sinha, Lee Ann @@aut@@ Oh, Myung Sook @@aut@@ Lee, Jong Kil @@aut@@
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Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. 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author	Kim, Namkwon
spellingShingle	Kim, Namkwon misc Alzheimer’s disease misc Microbiota-Gut-Brain axis misc Microfold cells misc Microglia Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
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topic_title	Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model Alzheimer’s disease (dpeaa)DE-He213 Microbiota-Gut-Brain axis (dpeaa)DE-He213 Microfold cells (dpeaa)DE-He213 Microglia (dpeaa)DE-He213
topic	misc Alzheimer’s disease misc Microbiota-Gut-Brain axis misc Microfold cells misc Microglia
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title	Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
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title_full	Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
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author_browse	Kim, Namkwon Ju, In Gyoung Jeon, Seung Ho Lee, Yeongae Jung, Min-Ji Gee, Min Sung Cho, Jae Seok Inn, Kyung-Soo Garrett-Sinha, Lee Ann Oh, Myung Sook Lee, Jong Kil
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title_sort	inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in alzheimer’s disease mouse model
title_auth	Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
abstract	Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. © The Author(s) 2023
abstractGer	Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. © The Author(s) 2023
abstract_unstemmed	Background The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. Conclusion Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications. © The Author(s) 2023
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title_short	Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
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Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown. Methods Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age. Results In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice. 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Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model

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