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Anti-Diabetic Potentials of Lactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats

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Abstract

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90 days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

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Data Availability

All the data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

Authors gratefully acknowledge the Indian Council of Medical Research (ICMR), New Delhi, India [No. 5/4/5-4/Diab.-16-NCD-II] for their financial support through a research grant to BA. We also thank DST-PURSE, DST-FIST, and MKU-RUSA 2.0 programs of Madurai Kamaraj University for the infrastructure and other facilities.

Funding

The authors sincerely acknowledge the financial support by the Indian Council of Medical Research, Government of India, New Delhi, through a research grant to BA [5/4/5–4/Diab.-16-NCD-II].

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MK: experimentation, data curation, formal analysis, prepared figures, validation, and writing original draft. TM: experimentation, writing review and editing. SK: experimentation, data curation, and editing. SG: experimentation, prepared figures and editing. PV: data curation, writing review, and editing. BA: conceptualization, supervision, project administration, writing review, prepared figures and editing.

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Correspondence to Balasubramaniem Ashokkumar.

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Kumar, M., Muthurayar, T., Karthika, S. et al. Anti-Diabetic Potentials of Lactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats. Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10221-7

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