March 3, 2026Open Access

A high fermentable fiber Western diet reduces indole levels

Key Points

Indole levels decreased significantly in the high fermentable fiber group compared to the Western diet group, indicating a protective effect from dietary modifications.
After 19 weeks, cecal metabolomic analysis revealed that fermentable fiber supplementation improves gut microbiota diversity and reduces oxidative stress markers.
Comparison of gene expression showed that CYP2E1 levels were higher in the WD group, contributing to metabolism that may lead to leaky gut and inflammation.
Findings support that a Western diet disrupts gut metabolism, suggesting fiber supplementation as an effective strategy for restoring balance in gut health.

Abstract

Changes in gut microbiota composition due to diet impact health. Fiber-rich diets promote beneficial microbiota and reduce the risk of metabolic diseases, while low-fiber, calorie-dense diets are linked to dysbiosis and increased disease risk. This study examines the effects of a Western diet (WD) and explores dietary fiber supplements as potential modifiers of those effects. 10-week-old C57Bl/6J male mice were fed control (low-fat) or WD (high-fat, high-sucrose) containing 0% fermentable fiber (FF) or WD supplemented with 20% FF (fructooligosaccharides, FOS; guar gum, GG, or pectin, Pec). After 19 weeks, analysis of the cecal metagenome using whole-genome shotgun sequencing, metabolome by untargeted and targeted LC-MS/MS, and tissue RNA and protein expression by RT-PCR and immunoblotting was undertaken. WD-FF reduced metabolic derangements from WD while also improving GM diversity and altering cecal metabolites, particularly tryptophan metabolism. A profound increase in cecal indole levels (targeted metabolomics) was noted in WD vs WD-FF groups. As the primary indole-oxidizing enzyme, CYP2E1 generates indoxyl sulfate, which contributes to oxidative stress and a leaky gut. Mice on WD displayed higher expression of Cyp2e1 mRNA in the gut. In the liver, the levels of both CYP2E1 protein and mRNA were higher in the WD group compared to the WD-FOS group, with protein levels also higher than in the WD-Pec group and mRNA levels higher than in the WD-GG group. mRNA expression of markers of oxidative stress, inflammation, and leaky barrier was significantly higher in the liver and intestine of the WD vs the WD-FF groups. FFs reduced high plasma indoxyl sulfate levels (except in WD-GG), and boosted short-chain fatty acids and indole acetic acid. Our data suggest that WD disrupts GM tryptophan metabolism, possibly by altering the balance between indole-producing and utilizing gut bacteria. Dietary fiber supplementation exerts protective effects, in part, by mitigating this imbalance.

Bookmark

View Full Paper

Cite This Study

Priyadarshini et al. (Fri,) studied this question.

synapsesocial.com/papers/69a75eafc6e9836116a29875 https://doi.org/https://doi.org/10.64898/2026.01.27.702025

Bookmark

View Full Paper