Amelioration of Type 2 Diabetes Using Four Strains of <i>Lactobacillus</i> Probiotics: Effects on Gut Microbiota Reconstitution-Mediated Regulation of Glucose Homeostasis, Inflammation, and Oxidative Stress in Mice

Song, Hainan; Xue, Hui; Zhang, Zeng; Wang, Jun; Li, Ao; Zhang, Jiachao; Luo, Pengfei; Zhan, Meng; Zhou, Xiaoli; Chen, Lihao; Fang, Yajing

doi:10.1021/acs.jafc.3c04665

Cited by 9 publications

(3 citation statements)

References 59 publications

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“…Feeding Bacteroides dorei and vulgatus to mice improved BAT BCAA catabolism, decreased circulating BCAA levels and body weight gain (44). Moreover, Bacteroides could be used as probiotics for treating aberrant metabolism, which is currently under active research (44)(45)(46). We found here that Bacteroides decreased in cecum, which could be related to the detrimental effect of valine on lipid metabolism in hepatic and adipose tissues.…”

Section: Discussionmentioning

confidence: 72%

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis

Zheng,

Wang,

Zhang

et al. 2024

Front. Nutr.

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IntroductionThe branched-chain amino acids (BCAAs) are essential to mammalian growth and development but aberrantly elevated in obesity and diabetes. Each BCAA has an independent and specific physio-biochemical effect on the host. However, the exact molecular mechanism of the detrimental effect of valine on metabolic health remains largely unknown.Methods and resultsThis study showed that for lean mice treated with valine, the hepatic lipid metabolism and adipogenesis were enhanced, and the villus height and crypt depth of the ileum were significantly increased. Transcriptome profiling on white and brown adipose tissues revealed that valine disturbed multiple signaling pathways (e.g., inflammation and fatty acid metabolism). Integrative cecal metagenome and metabolome analyses found that abundances of Bacteroidetes decreased, but Proteobacteria and Helicobacter increased, respectively; and 87 differential metabolites were enriched in several molecular pathways (e.g., inflammation and lipid and bile acid metabolism). Furthermore, abundances of two metabolites (stercobilin and 3-IAA), proteins (AMPK/pAMPK and SCD1), and inflammation and adipogenesis-related genes were validated.DiscussionValine treatment affects the intestinal microbiota and metabolite compositions, induces gut inflammation, and aggravates hepatic lipid deposition and adipogenesis. Our findings provide novel insights into and resources for further exploring the molecular mechanism and biological function of valine on lipid metabolism.

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Section: Discussionmentioning

confidence: 72%

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis

Zheng,

Wang,

Zhang

et al. 2024

Front. Nutr.

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“…42 Although a number of antidiabetic drugs are available, long-term use can lead to side effects. 43 Numerous in vitro research studies and in vivo studies in animals have proved that probiotics, especially lactic acid bacteria, have great potential and good prospects in the treatment and prevention of T2DM, 44,45 but the specific mechanism of probiotics in T2DM is not yet fully understood. Therefore, the continuous exploration and identification of new lactic acid bacteria with hypoglycemic effects is of clinical significance, and further clarification of their mechanism will hopefully provide new ideas and opportunities for the prevention and treatment of T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress is therefore also considered to be one of the factors in the onset and development of diabetes. 45,49 GSH-Px, CAT, and SOD are the primary antioxidant enzymes that defend our body against harmful ROS. 60 MDA is a marker of oxidative stress and is the product of lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Latilactobacillus sakei QC9 alleviates hyperglycaemia in high-fat diet and streptozotocin-induced type 2 diabetes mellitus mice via the microbiota–gut–liver axis

Chen,

Pan,

Zhang

et al. 2024

Food Funct.

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Strain‐Level Screening of Human Gut Microbes Identifies Three Lactobacillus Strains as Next‐Generation Antidiabetic Probiotics

Yang,

Li,

Zhang

et al. 2024

Food Frontiers

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia. Probiotic supplementation improves glucolipid metabolism by modulating the gut microbiota. However, current research lacks a systematic understanding of the overall hypoglycemic ability of human gut microbes. First, a high‐throughput screening platform based on HepG2 cells was developed to screen candidate strains with hypoglycemic potential. Subsequently, we utilized a T2DM mouse model to investigate the antidiabetic effects and mechanisms of three selected Lactobacillus strains through biochemical analyses, histopathological analyses, RNA‐seq analyses, and metagenomics analyses. We categorized and ranked the hypoglycemic ability of 4811 strains belonging to 8 phyla, 17 orders, 68 genera, and 241 species. The hypoglycemic ability of all tested strains showed a significant normal distribution, and several species with significant efficacy were screened, primarily from Bifidobacterium and Lactobacillus. Subsequently, we found that three Lactobacillus strains significantly improve glycolipid metabolism disorders in T2DM mice, and the mechanisms include inhibiting hepatic gluconeogenesis via the AKT–FOXO1–PEPCK/G6pase pathway and activating GPR41 and GPR43 to bind short‐chain fatty acids, promoting glucagon‐like peptide‐1 (GLP‐1) secretion. These strains also significantly regulate the gut microbiota structure and composition, contributing to their hypoglycemic effects. This study comprehensively examined the hypoglycemic efficacy of 4811 strains for the first time, resulting in a functional map of human gut microbiota for hypoglycemia. Additionally, we investigated the hypoglycemic efficacy and the mechanisms of three Lactobacillus strains. This study provides a rich bacterial pool for the targeted development of probiotics as potential treatments for diabetes and related metabolic diseases.

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Amelioration of Type 2 Diabetes Using Four Strains of Lactobacillus Probiotics: Effects on Gut Microbiota Reconstitution-Mediated Regulation of Glucose Homeostasis, Inflammation, and Oxidative Stress in Mice

Cited by 9 publications

References 59 publications

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis

Latilactobacillus sakei QC9 alleviates hyperglycaemia in high-fat diet and streptozotocin-induced type 2 diabetes mellitus mice via the microbiota–gut–liver axis

Strain‐Level Screening of Human Gut Microbes Identifies Three Lactobacillus Strains as Next‐Generation Antidiabetic Probiotics

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