# Gut dysbiosis and immune dysfunction induced by chronic cola replacement of water in rats: not just a sugar problem

**Authors:** Huijie Gao, Wanru Li, Xin Wang, Yan Ren, Xiao Li, Chao Liu

PMC · DOI: 10.3389/fnut.2025.1707842 · Frontiers in Nutrition · 2026-02-04

## TL;DR

Replacing water with cola for 8 weeks in rats caused gut microbiome changes and immune and kidney issues, regardless of sugar content.

## Contribution

A novel rat model shows that long-term cola consumption, even sugar-free, disrupts gut microbiota and harms immune and renal health.

## Key findings

- Both sugar-sweetened and diet cola caused immune suppression and changes in gut microbiota diversity and abundance.
- Diet cola led to elevated transaminases, while sugar cola increased renal stress markers like blood urea nitrogen.
- Microbiota shifts correlated with immune organ indices and kidney function indicators.

## Abstract

Excessive sugar-sweetened beverage consumption like cola is a worldwide public health problem. However, the effects and mechanisms of replacing water with cola (either as sugar-free cola or sugar-sweetened cola) on intestinal microbiota and overall health remain unknown, prompting this investigation.

To address this, we created a new experimental model in which cola completely replaced drinking water. Twenty-four Sprague-Dawley rats were randomly divided into three groups (n = 8): water, cola (sugar-sweetened), diet cola, for an 8-week intervention. Body weight, body length, BMI, organ indices, hematological, and serum biochemical parameters, and gut microbiota (16S rRNA gene sequencing) were determined.

Both colas resulted in immune suppression (lower thymus index and leukopenia) and decreased total protein. The cola group showed renal stress [higher blood urea nitrogen, (BUN)] and a significant increase in spleen index. The diet cola induced a significant transaminases elevation compared to the cola group. Both colas significantly altered intestinal microbiota structure, including changes in diversity and abundance (e.g., shifts in Firmicutes and Bacteroidota proportions and in the abundance of Ligilactobacillus and Lactobacillus). Co-abundance network showed complicated relationships, mostly involving Lactobacillus, Romboutsia, and other taxa. Furthermore, Bacteroidota and unclassified Lactobacillus were significantly correlated with immune organ indices (thymus, spleen) and BUN.

Using an innovative model of complete water replacement, our study demonstrates that long-term cola consumption-whether or not sugar containing-has significant perturbative effects on gut microbiota and impairs immune and renal function. These results should warn of the impacts of regular cola intake and the need for further scrutiny of artificial sweeteners.

## Full-text entities

- **Genes:** Alb (albumin) [NCBI Gene 24186] {aka Alb1, Albza}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}
- **Diseases:** insulin resistance (MESH:D007333), colitis (MESH:D003092), immune dysfunction (MESH:D007154), Thymic atrophy (MESH:D013953), type II diabetes mellitus (MESH:D003924), IBD (MESH:D015212), chronic diseases (MESH:D002908), hyperplasia (MESH:D006965), inflammation (MESH:D007249), liver disease (MESH:D008107), Gut dysbiosis (MESH:D064806), diabetes (MESH:D003920), leukocytopenia (MESH:D007970), hepatic steatosis (MESH:D005234), splenomegaly (MESH:D013163), obesity (MESH:D009765), metabolic diseases (MESH:D008659)
- **Chemicals:** caffeine (MESH:D002110), Sugar-sweetened cola (-), ZR- (MESH:D015040), phenylalanine (MESH:D010649), aspartic acid (MESH:D001224), phosphoric acid (MESH:C030242), sucrose (MESH:D013395), lipid (MESH:D008055), fructose (MESH:D005632), Crea (MESH:D003404), glucose (MESH:D005947), SCFA (MESH:D005232), Sugar (MESH:D000073893), fat (MESH:D005223), methanol (MESH:D000432), TG (MESH:D014280), isoflurane (MESH:D007530), Aspartame (MESH:D001218), Water (MESH:D014867), Cholesterol (MESH:D002784), Blood glucose (MESH:D001786)
- **Species:** Bacteroidota (Bacteroides-Cytophaga-Flexibacter group, phylum) [taxon 976], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Quinella (genus) [taxon 1567], Bacteroides (genus) [taxon 816], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Lachnospiraceae (family) [taxon 186803], Lactobacillus (genus) [taxon 1578], Mus musculus (house mouse, species) [taxon 10090], Pseudomonadota (proteobacteria, phylum) [taxon 1224]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913579/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913579/full.md

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Source: https://tomesphere.com/paper/PMC12913579