PMID- 32332068 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20221207 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 8 IP - 1 DP - 2020 Apr TI - Lactobacillus salivarius AP-32 and Lactobacillus reuteri GL-104 decrease glycemic levels and attenuate diabetes-mediated liver and kidney injury in db/db mice. LID - 10.1136/bmjdrc-2019-001028 [doi] LID - e001028 AB - OBJECTIVES: Patients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM. RESEARCH DESIGNS AND METHODS: Sugar consumption by more than 20 strains of Lactobacillus species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy. RESULTS: Among the tested strains, Lactobacillus salivarius AP-32 and L. reuteri GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na(+)-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury. CONCLUSION: Our data elucidate a novel role for probiotics in glycemic regulation in the host. L. salivarius AP-32 and L. reuteri GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Hsieh, Pei-Shan AU - Hsieh PS AD - Research and Development Department, Glac Biotech Co., Ltd, Tainan, Taiwan. FAU - Ho, Hsieh-Hsun AU - Ho HH AD - Research and Development Department, Glac Biotech Co., Ltd, Tainan, Taiwan. FAU - Hsieh, Shih-Hung AU - Hsieh SH AD - Research and Development Department, Glac Biotech Co., Ltd, Tainan, Taiwan. FAU - Kuo, Yi-Wei AU - Kuo YW AD - Research and Development Department, Glac Biotech Co., Ltd, Tainan, Taiwan. FAU - Tseng, Hsiu-Ying AU - Tseng HY AD - Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Kao, Hui-Fang AU - Kao HF AD - Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan. FAU - Wang, Jiu-Yao AU - Wang JY AUID- ORCID: 0000-0003-4540-9822 AD - Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan a122@mail.ncku.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 SB - IM MH - Animals MH - Caco-2 Cells MH - *Diabetes Mellitus, Experimental MH - *Diabetes Mellitus, Type 2/therapy MH - Humans MH - Kidney MH - *Limosilactobacillus reuteri MH - *Ligilactobacillus salivarius MH - Liver MH - Mice PMC - PMC7202753 OTO - NOTNLM OT - hexokinase OT - microbiology OT - nutrient regulation OT - type 2 diabetes COIS- Competing interests: P-SH, H-HH, S-HH and Y-WK are employers of Glac Biotech Co, Ltd, Tainan City, Taiwan. EDAT- 2020/04/26 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/04/23 CRDT- 2020/04/26 06:00 PHST- 2019/11/12 00:00 [received] PHST- 2020/02/27 00:00 [revised] PHST- 2020/03/24 00:00 [accepted] PHST- 2020/04/26 06:00 [entrez] PHST- 2020/04/26 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/04/23 00:00 [pmc-release] AID - 8/1/e001028 [pii] AID - bmjdrc-2019-001028 [pii] AID - 10.1136/bmjdrc-2019-001028 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2020 Apr;8(1):e001028. doi: 10.1136/bmjdrc-2019-001028.