Stem Cell Transcription Factor FoxO Controls Microbiome Resilience in Hydra

The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept

Image_1.PNG

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model

Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question of whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberries are rich in dietary fibers, the extent of microbiome modulation by polyphenols, particularly proanthocyanidins (PACs), remains to be shown. Since previous work has only focused on long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, PAC-rich cranberry juice extract (CJE) on the short-term dynamics of a human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57%), the highest ever utilized in a microbiome study. In a 37-day experiment with a ten-day CJE intervention and 14-day recovery phase, we profiled the microbiota via 16S rRNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamic patterns in bacterial abundances during and after treatment, before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of Akkermansia muciniphila and Clostridium hiranonis at the expense of Bacteroides ovatus after the offset of the selection pressure imposed by the PAC-rich CJE. This demonstrates that termination of an intervention with a cranberry product can induce changes of a magnitude as high as the intervention itself

Image_4.PNG

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Image_2.PNG

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Table_2.XLSX

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Table_3.XLSX

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Image_3.PNG

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p

Table_1.XLSX

<p>The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra, one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator. However, how environmental factors interact with FoxO remains unknown. Here, we find that deficiency in FoxO signaling in Hydra leads to dysregulation of antimicrobial peptide expression and that FoxO loss-of-function polyps are impaired in selection for bacteria resembling the native microbiome and more susceptible to colonization of foreign bacteria. These findings reveal a key role of FoxO signaling in the communication between host and microbiota and embed the evolutionary conserved longevity factor FoxO into the holobiont concept.</p