Thevenin, J. | bioRxiv Science

bioRxiv2024

Pathogenicity of Commensal Gut Biofilm In Prefrail Aging

Pathophysiological mechanisms of unhealthy aging, particularly the transition from robustness to frailty, remain poorly understood. Despite extensive microbiome research on taxonomy, the behavior of early prefrail gut bacteria in their natural community-host mucosal tissue context remains unexplored. Using fecal samples from the INSPIRE-T aging human cohort, we characterized gut microbiota phenotype during prefrailty stages using a polymicrobial biofilm model. Results revealed that prefrail-derived biofilms exhibited distinct taxonomic and physical alterations, enhanced dispersal, and increased epithelial virulence compared to robust counterparts. Multiparametric analyses linked biofilm characteristics to clinical traits, suggesting their potential as aging status indicators. Polyphenol-rich grape pomace extract partially reversed prefrail biofilm alterations and reduced proinflammatory prefrail biofilm responses in vitro. Microbiota from prefrail aged mice induced colon damage in antibiotic-treated recipients, establishing a prefrail microbiome-inflammation causality. Overall, the findings identified novel prefrail microbiome characteristics, established causal inflammatory links, and support microbiota-targeted geroprotective interventions for the prefrail populations.

microbiology↗

bioRxiv2023

The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice

As a functional component of erythrocyte hemoglobin, iron is essential for oxygen delivery to all tissues in the body. The liver-derived peptide hepcidin is the master regulator of iron homeostasis. During anemia, the erythroid hormone erythroferrone regulates hepcidin synthesis to ensure adequate supply of iron to the bone marrow for red blood cells production. However, mounting evidence suggested that another factor may exert a similar function. We identified the hepatokine FGL1 as a previously undescribed suppressor of hepcidin that is induced in the liver in response to hypoxia during the recovery from anemia and in thalassemic mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo. Deletion of Fgl1 in mice results in a blunted repression of hepcidin after bleeding. FGL1 exerts its activity by direct binding to BMP6, thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription. Key points1/ FGL1 regulates iron metabolism during the recovery from anemia. 2/ FGL1 is an antagonist of the BMP/SMAD signaling pathway.

physiology↗