Low dietary fiber intake impairs small intestinal Th17 and intraepithelial T cell development over generations

Area of Science:

• Microbiome research
• Immunology
• Nutritional science

Background:

• Dietary fiber significantly influences gut microbiota composition and function.
• The small intestinal (SI) microbiota plays a critical role in host immunity.

Purpose of the Study:

• To investigate the impact of low-fiber diets on SI microbiota and T cell development.
• To determine if dietary fiber supplementation or microbiota restoration can reverse these effects.
• To assess the long-term consequences of low-fiber diets on immune function and susceptibility to infection.

Main Methods:

• Feeding mice with low-fiber or fiber-rich diets.
• Analyzing SI microbiota composition using 16S rRNA sequencing.
• Assessing T cell populations (Th17, TCRαβ+CD8αβ+, TCRαβ+CD8αα+) in the SI.
• Performing microbiota transplantation experiments.
• Evaluating host susceptibility to Citrobacter rodentium infection.

Main Results:

• Low-fiber diets altered the SI microbiota and impaired T cell development.
• Dietary fiber supplementation partially restored T cell development, but defects persisted across generations.
• Offspring of low-fiber fed mice showed reduced SI T cells even on a fiber-rich diet.
• Microbiota transplantation from fiber-fed mice combined with a fiber-rich diet was necessary to fully restore T cell development in offspring.
• Low-fiber diets reduced segmented filamentous bacteria (SFB) abundance, affecting vertical transmission.
• Low-fiber diet-induced T cell defects increased susceptibility to Citrobacter rodentium infection.

Conclusions:

• Dietary fiber is essential for maintaining a healthy SI microbiota and proper T cell development.
• Low-fiber diets can lead to persistent, transgenerational immune defects due to altered microbiota vertical transmission.
• Restoring specific bacteria like SFB and ensuring adequate fiber intake are critical for immune resilience.