Impact of a Sucrose-Excluded Low-Fat Diet on Metabolic Health via Gut Microbiome Disruption and Colonic Inflammation in Murine Models

By
Nourah Almansour
Shihab Kochumon
Fatema Al-Rashed
Md Zubbair Malik
Noelle Benobaid
Steve Shenouda
Reeby Thomas
Hossein Arefanian
Rasheeba Nizam
Texy Jacob
Ashraf Al Madhoun
Jaakko Tuomilehto
Fahd Al-Mulla
Rasheed Ahmad
July 21, 2026

Frontiers In Immunology

Overview

This study investigates the effects of a sucrose-free low-fat diet (SF-LFD) on metabolic health in murine models, revealing significant disruptions in gut microbiota and metabolic parameters. SF-LFD led to impaired glucose tolerance, altered metabolic hormones, and pronounced colonic inflammation.

Background

Low-fat diets are commonly recommended for metabolic health, yet the specific impact of sucrose elimination within these diets is not well understood. This research highlights the potential adverse effects of a sucrose-free low-fat diet on metabolic parameters and gut health.

Data Highlights

Parameter	SF-LFD	C-LFD
Body Weight	Unchanged	Unchanged
Liver Weight	Unchanged	Unchanged
Glucose Tolerance	Impaired	Normal
Insulin Sensitivity	Reduced	Normal
Inflammatory Mediators	Increased	Normal

Key Findings

SF-LFD resulted in impaired glucose tolerance and reduced insulin sensitivity.
Circulating metabolic hormones were altered, with elevated C-peptide, incretins, ghrelin, and resistin.
Gut microbiota diversity was significantly disrupted, with depletion of beneficial taxa.
Colonic inflammation was characterized by crypt disruption and increased immune cell infiltration.
Hepatic inflammation and microvesicular steatosis were observed following SF-LFD feeding.

Clinical Implications

The findings suggest that sucrose exclusion from low-fat diets may lead to metabolic dysfunction and gut inflammation. Clinicians should consider the implications of dietary composition on metabolic health when advising patients on dietary changes.

Conclusion

This study highlights the potential negative effects of a sucrose-free low-fat diet on metabolic health and gut microbiota, emphasizing the need for further research in dietary guidelines.