Abstract
Age-related gut barrier dysfunction and dysbiosis of the gut microbiome play crucial roles in human aging. Dietary methionine restriction (MR) has been reported to extend lifespan and reduce the inflammatory response; however, its protective effects on age-related gut barrier dysfunction remain unclear. Accordingly, we focus on the effects of MR on inflammation and gut function. We found a 3-month methionine-restriction reduced inflammatory factors in the serum of aged mice. Moreover, MR reduced gut permeability in aged mice and increased the levels of the tight junction proteins mRNAs, including those of occludin, claudin-1, and zona occludens-1. MR significantly reduced bacterial endotoxin lipopolysaccharide concentration in aged mice serum. By using 16s rRNA sequencing to analyze microbiome diurnal rhythmicity during 24 h, we found MR moderately recovered the cyclical fluctuations of the gut microbiome which was disrupted in aged mice, leading to time-specific enhancement of the abundance of short-chain fatty acid-producing and lifespan-promoting microbes. Moreover, MR dampened the oscillation of inflammation-related TM7-3 and Staphylococcaceae. In conclusion, the effects of MR on the gut barrier were likely related to alleviation of the oscillations of inflammation-related microbes. MR can enable nutritional intervention against age-related gut barrier dysfunction.
Highlights
Aging is accompanied by a decline in the functional capacity of body systems, including cognitive, cardiovascular, and physiological health
We found that intestinal tight junction proteins were upregulated and the age-related rhythmic disturbance of intestinal bacteria was alleviated by methionine restriction (MR)
We found that MR reduced the levels of serum LPS and inflammatory factors in aged mice, which may be related to enhancement of the integrity of the intestinal barrier and upregulation of tight junction proteins by MR
Summary
Aging is accompanied by a decline in the functional capacity of body systems, including cognitive, cardiovascular, and physiological health. The gut has been reported to play crucial roles in the aging process [1]. Aging can alter microbial abundance and cause microbiota dysbiosis [2]. Loss of gut microbiota diversity can increase chronic low-grade inflammation and reduce cognitive function during aging [3]. The gut microbes could produce short-chain fatty acids (SCFAs) from carbohydrate fermentation. It has been reported that Sutterella, Bacteroides, Lactobacillus, Prevotella and Bacteroidales are SCFAs producing microbe [4]. Desulfovibrionaceae, Staphylococcus, and Ruminococcaceae lipopolysaccharidesare has been reported to be associated with the microbiota inflammatory properties [5, 6]. Several studies have revealed that elderly adults
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