Abstract
Gut microbiota modulate age-associated changes in metabolism, innate immune responses, and cognitive function. However, the involvement of host factors in the regulation of age-dependent gut microbial structure and intestinal inflammation is largely unknown. Lipocalin 2 (Lcn2) has previously been identified as an adipocytokine and characterized as an important regulator of diet-induced obesity and inflammation. Previous studies have shown that Lcn2 plays a role in high fat diet-induced reshaping of gut microbiota and intestinal inflammation. However, the role of Lcn2 in the regulation of aging-related reshaping of gut microbiota is unclear. Herein, we demonstrate that fecal levels of Lcn2 are reduced during aging. Age reshaped gut microbiota composition in wild-type (WT) mice. Interestingly, Lcn2 deficiency diminished this effect of aging in Lcn2 knockout (LKO) mice, leading to decreased bacterial diversity and increased Firmicutes to Bacteroidetes (F to B) ratio. Specifically, we identified 16 bacteria at the family level that were differentially abundant between WT and LKO mice at old age. Several health-promoting bacteria, including SCFA-producing bacteria, were significantly less prevalent in old LKO mice compared to WT mice, indicating that Lcn2 deficiency shifts the aging-related gut microbial community towards an unhealthy population and lowers microbial butyrate production. Our results provide a line of evidence that Lcn2 plays a role in the control of aging-related reshaping of gut microbiota composition and metabolites.
Highlights
A recent study reported that gut microbiota and colonic gene expression are profoundly changed during aging, which is associated with diminished colonic health [13]
Age-associated alterations in colonic gene expression are associated with increased intestinal permeability, modulated gut microbiota composition, and increased systemic inflammation [13,36]
Lipocalin 2 (Lcn2) in the colon was increased, but Lcn2 secretion into the gut lumen was decreased, in old mice compared to young mice, suggesting that the secretory pathways of Lcn2 into the gut lumen are impaired with aging
Summary
In large human cohort studies, remarkable gut microbiota remodeling was observed in elderly populations over 65 years old [2,3,4,5,6,7]
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