ArticleNutrition research and practice2026
Amelioration of chronic inflammation, insulin resistance, and gut microbiota homeostasis by a combination of
Article in Nutrition research and practice, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
objectivesTo examine the effects of a combination of live MATERIALS/
methodsObese T2DM mice were established by feeding mice a high-fat diet for four weeks, followed by a single intraperitoneal injection of streptozotocin (100 mg/kg). The mice were then divided randomly into 5 groups (n = 8/group): normal control (NC), T2DM model, CBLEB (585 mg/kg/d, by gavage), dimethylbiguanide (DMBG, 200 mg/kg/d, by gavage), and CBLEB+DMBG combination. All treatments were administered daily for four weeks. The body weight and fasting blood glucose were monitored weekly. An oral glucose tolerance test was performed to assess the glucose tolerance. The serum levels of lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), insulin, and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10, and lipopolysaccharide) were measured by enzyme-linked immunosorbent assay. Pancreatic IL-6 and TNF-α expression was detected by immunohistochemistry. The histopathological changes in the pancreas, colon, and adipose tissues were evaluated by hematoxylin and eosin staining. The protein expression of insulin receptor substrate 1 (IRS-1)/p-IRS-1 (Ser307), Toll-like receptor 4 (TLR4)/MyD88, tight junction proteins (zonula occludens protein 1 [ZO-1]/claudin 1 [CLDN1]/occludin), and B-cell lymphoma/leukemia-2 (Bcl-2)-associated X protein A (BAX)/Bcl-2 was analyzed by Western blot. The gut microbiota composition was profiled by 16S rRNA gene sequencing.
resultsCBLEB significantly improved the weight gain, hyperglycemia, insulin resistance (IR), dyslipidemia, reduced adipocyte size, suppressed systemic inflammation, and alleviated pancreatic and colonic damage in T2DM mice. The combination of CBLEB and DMBG showed the most pronounced improvements in metabolic and inflammatory parameters. Western blot showed that CBLEB inhibited TLR4/MyD88 signaling, enhanced insulin signaling (IRS-1/p-IRS-1), repaired the intestinal barrier (ZO-1/CLDN1/occludin), and regulated the apoptotic balance (BAX/Bcl-2). Gut microbiota analysis suggested that CBLEB remodeled the gut microbiota, with a functional prediction suggesting shifts in the metabolic pathways and a decrease in the abundance of
conclusionCBLEB ameliorated systemic inflammation and IR in obese T2DM mice through gut microbiota modulation, intestinal barrier restoration, and suppression of inflammatory pathways.
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