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Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
Methionine Restriction Improves Gut Barrier Function by Reshaping Diurnal Rhythms of Inflammation-Related Microbes in
Bo Ren1,2, Luanfeng Wang1, Aiziguli Mulati1
1Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China.
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.
Insights
Dietary methionine restriction (MR) improves gut barrier function in aging mice by reducing inflammation and restoring beneficial gut microbes. This nutritional intervention may combat age-related gut dysfunction.
Area of Science:
- Gerontology
- Gastroenterology
- Microbiology
Background:
- Age-related gut barrier dysfunction and dysbiosis are key factors in aging.
- Dietary methionine restriction (MR) is known to extend lifespan and reduce inflammation, but its effects on gut barrier health are unclear.
Purpose of the Study:
- To investigate the impact of MR on age-related gut barrier dysfunction, inflammation, and microbiome alterations in mice.
Main Methods:
- A 3-month methionine restriction diet was administered to aged mice.
- Serum inflammatory factors, gut permeability, tight junction protein mRNA levels, and lipopolysaccharide concentrations were measured.
- 16S rRNA sequencing analyzed gut microbiome diurnal rhythmicity and microbial composition.
Main Results:
- MR reduced serum inflammatory factors and gut permeability in aged mice.
- MR increased tight junction protein mRNA levels (occludin, claudin-1, zona occludens-1) and decreased serum lipopolysaccharide.
- MR partially restored disrupted gut microbiome diurnal fluctuations, enhancing beneficial microbes and dampening inflammation-related bacteria.
Conclusions:
- Methionine restriction alleviates age-related gut barrier dysfunction by reducing inflammation and restoring microbiome rhythmicity.
- MR represents a potential nutritional intervention strategy against age-related gut barrier decline.
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