# Novel probiotic Lactobacillus helveticus WIS02 alleviates diabetes through multi-pronged regulation of glycolipid metabolism, pancreatic protection and gut microbiota remodeling

**Authors:** Shuang Guo, Yuying Li, Yanan Yang, Yuexiao Jiang, Yufeng Wang, Ying Cao, Yunfeng Duan, Chongming Wu

PMC · DOI: 10.3389/fmicb.2025.1735605 · Frontiers in Microbiology · 2026-01-21

## TL;DR

A new probiotic strain, Lactobacillus helveticus WIS02, reduces diabetes symptoms in mice by improving blood sugar and lipid levels, protecting organs, and changing gut bacteria.

## Contribution

L. helveticus WIS02 is shown to alleviate diabetes through glycolipid regulation, tissue protection, and gut microbiota remodeling in a mouse model.

## Key findings

- WIS02 reduced fasting blood glucose by 66.0% and improved glucose tolerance in diabetic mice.
- WIS02 treatment lowered cholesterol and triglyceride levels and protected liver, pancreatic, and colon tissues.
- WIS02 increased beneficial gut bacteria like Akkermansia muciniphila and Parabacteroides distasonis, which correlated with better metabolic health.

## Abstract

Diabetes mellitus poses a global health burden with limited therapies derived from breast milk targeting its systemic complications. Probiotics like Lactobacillus helveticus show metabolic benefits, but strain-specific efficacy and mechanisms remain unclear.

This study evaluated L. helveticus WIS02’s therapeutic potential in streptozotocin (STZ)-induced diabetic mice, focusing on glycemic control, tissue protection, and gut microbiota modulation.

We found pre-administration of WIS02 for 7 days reduced the final fasting blood glucose by 66.0% and improved oral glucose tolerance (AUC decreased by 51.6%). Additionally, WIS02 significantly mitigated dyslipidemia (TC decreased by 23.6%, TG decreased by 39.5%) and alleviated tissue damage to the liver, pancreatic, and colon tissues. Microbiota analysis revealed that WIS02 treatment significantly altered the gut microbiota structure, increasing the proportion of beneficial bacteria, particularly Akkermansia muciniphila and Parabacteroides distasonis. Correlation analysis between microbiota abundance and physiological indicators showed that Parabacteroides distasonis, Oscillibacter valericigenes, and Akkermansia muciniphila were significantly negatively correlated with blood glucose and lipid levels, while positively correlated with insulin and hepatic glycogen levels.

L. helveticus WIS02 exhibits multi-targeted efficacy against diabetes by regulating glycolipid metabolism, protecting tissues, and remodeling gut microbiota. These findings highlight its potential as a novel probiotic for metabolic disorder management, warranting clinical translation.

## Linked entities

- **Diseases:** diabetes mellitus (MONDO:0005015)
- **Species:** Lactobacillus helveticus (taxon 1587), Akkermansia muciniphila (taxon 239935), Parabacteroides distasonis (taxon 823), Oscillibacter valericigenes (taxon 351091)

## Full-text entities

- **Genes:** Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 20787] {aka ADD1, SREBP1, bHLHd1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Sis (sucrase isomaltase) [NCBI Gene 69983] {aka 2010204N08Rik, SI, Si-s}, Slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) [NCBI Gene 20528] {aka GT2, Glut-4, Glut4, twgy}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cog2 (component of oligomeric golgi complex 2) [NCBI Gene 76332] {aka 1190002B08Rik, 2700012E02Rik, Ldlc}
- **Diseases:** T2D (MESH:D003924), renal impairment (MESH:D007674), hepatic damage (MESH:D056486), beta-cell dysfunction (MESH:D007340), T1D (MESH:D003922), liver injury (MESH:D017093), TC (MESH:C535937), -cell damage (MESH:D002280), tissue damage (MESH:D017695), diabetic foot ulcers (MESH:D017719), endotoxemia (MESH:D019446), hyperglycemic (MESH:D006944), disorders of glucose and lipid metabolism (MESH:D052439), diabetes complications (MESH:D048909), hypoglycemia (MESH:D007003), cardiovascular and renal complications (MESH:D002318), polydipsia (MESH:D059606), ulcers (MESH:D014456), insulin deficiency (MESH:D007333), weight gain (MESH:D015430), gestational diabetes (MESH:D016640), obese (MESH:D009765), hyperphagia (MESH:D006963), vascular complications (MESH:D003925), hypotensive (MESH:D007022), metabolic disorder (MESH:D008659), inflammation (MESH:D007249), hyperglycemia (MESH:D006943), Dyslipidemia (MESH:D050171), beta-cell failure (MESH:D051437), DM (MESH:D003920), prediabetes (MESH:D011236), edema (MESH:D004487), pancreatic injury (MESH:D010195), neuroinflammation (MESH:D000090862), atrophy (MESH:D001284)
- **Chemicals:** paraformaldehyde (MESH:C003043), lipid (MESH:D008055), eosin (MESH:D004801), PBS (MESH:D007854), glucose (MESH:D005947), short-chain fatty acids (MESH:D005232), DHA (MESH:C027493), FBG (-), H&amp;E (MESH:D006371), bile acid (MESH:D001647), TG (MESH:D013866), oligofructose (MESH:C120489), Glycerol (MESH:D005990), hematoxylin (MESH:D006416), fatty acid (MESH:D005227), carbohydrate (MESH:D002241), water (MESH:D014867), Metformin (MESH:D008687), glycogen (MESH:D006003), Sulfonylureas (MESH:D013453), STZ (MESH:D013311), glycolipid (MESH:D006017), ethanol (MESH:D000431), cholesterol (MESH:D002784), blood glucose (MESH:D001786), insulin (MESH:D007328), Met (MESH:D008715), paraffin (MESH:D010232), acid (MESH:D000143), salt (MESH:D012492), TC (MESH:D013667), polysaccharides (MESH:D011134), xylene (MESH:D014992), omega-3 fatty acids (MESH:D015525), nitrogen (MESH:D009584), TG (MESH:D014280), pentobarbital sodium (MESH:D010424)
- **Species:** Bifidobacterium animalis (species) [taxon 28025], Parabacteroides sp. (species) [taxon 1869337], Bacteroides caecimuris (species) [taxon 1796613], Staphylococcus xylosus (species) [taxon 1288], Bacteroidia (class) [taxon 200643], Bifidobacterium angulatum (species) [taxon 1683], Akkermansia muciniphila (species) [taxon 239935], Malaciobacter marinus (species) [taxon 505249], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Rodentia (rodent, order) [taxon 9989], Faecalibacterium prausnitzii (species) [taxon 853], Homo sapiens (human, species) [taxon 9606], Muribaculum intestinale (species) [taxon 1796646], Parabacteroides distasonis (species) [taxon 823], Helicobacter cinaedi (species) [taxon 213], Lactobacillus helveticus (species) [taxon 1587], Bacteroides coprosuis (species) [taxon 151276], Bacteroides ovatus (species) [taxon 28116], Lactobacillus jensenii (species) [taxon 109790], Lachnoclostridium phocaeense (species) [taxon 1871021], Helicobacter bilis (species) [taxon 37372], Bifidobacterium longum (species) [taxon 216816], Escherichia coli (E. coli, species) [taxon 562], Oscillibacter valericigenes (species) [taxon 351091], Helicobacter canadensis (species) [taxon 123841], Mus musculus (house mouse, species) [taxon 10090], Lacticaseibacillus rhamnosus (species) [taxon 47715], Burkholderiales bacterium YL45 (species) [taxon 1834205], Staphylococcus nepalensis (species) [taxon 214473]

## Full text

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## Figures

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## References

43 references — full list in the complete paper: https://tomesphere.com/paper/PMC12910836/full.md

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Source: https://tomesphere.com/paper/PMC12910836