A reduced calorie intake improves health via numerous mechanisms, of which upregulation of the cellular maintenance processes of autophagy is likely the most important. Restricting the intake of selected essential amino acids, particularly methionine, has similar effects, as detection of essential amino acids appears to be the primary way by which cells perform nutrient sensing. Most research to date has focused on the effects of reduced calorie intake on the cells and organs of the body. What about the gut microbiome, however, in light of the new research of recent years indicating its importance in health?
We might ask: to what degree are the long-term benefits of calorie restriction, intermittent fasting, and protein restriction (such as methionine restriction) driven by changes in the gut microbiome? Thus, what are our expectations for the benefits resulting from engineering a better gut microbiome? How interested should we be in approaches such as fecal microbiota transplantation and flagellin immunization that can rejuvenate the aged gut microbiome? These are interesting questions, still in the early stages of exploration in the research community.
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 over 24 hour, 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.