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Glucose-responsive probiotics for glycaemic modulation in mice and monkeys

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Why This Matters

This study highlights the potential of glucose-responsive probiotics, specifically GIFT GLP-1, to modulate glycemic levels and reduce inflammation and oxidative stress in diabetic models. Such innovations could pave the way for novel, less invasive treatments for diabetes and its complications, benefiting both the healthcare industry and patients. The research underscores the importance of microbiome-based therapies in managing metabolic diseases, offering promising avenues for future therapeutic development.

Key Takeaways

a, Representative hematoxylin and eosin (H&E) staining from liver tissue sections. Scale bars, 100 μm or 50 μm. The rectangular frame indicates the area displayed at a higher magnification. b, c, Hepatic TG (b), and T-CHO (c) levels of db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. d, e, Hepatic levels of IL-1β (d) and TNF-α (e) in db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. f-i, Ameliorating effect of GIFT GLP-1 on oxidative stress in diabetic mouse liver. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP−1 , livers of db/db mice were harvested and homogenized. The levels of oxidative stress markers were measured, including MDA (f), SOD (g), GSH (h), and T-AOC (i). j, k, Renal levels of IL-1β (j) and TNF-α (k) in db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. l-o, Ameliorating effect of GIFT GLP-1 on oxidative stress in diabetic mouse kidney. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP-1 , the kidneys of db/db mice were harvested and homogenized. The levels of oxidative stress markers were measured, including MDA (l), SOD (m), GSH (n), and T-AOC (o). p-u, Effect of GIFT GLP-1 on alleviating renal damage. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP-1 , serum levels of creatinine (CRE) (p), blood urea nitrogen (BUN) (q), and urine protein (r) in db/db mice were measured. Kidneys were harvested and weighed, and the kidney-to-body weight ratios (s) were calculated. Histopathological analyses of kidney sections, including H&E staining, Masson’s trichrome staining, and PAS staining (t), were performed. Scale bars, 50 μm. u, Masson’s trichrome staining to quantify glomerular fibrosis (20 glomeruli per mouse were analyzed, n = 5 mice per group). v, w Colonic IL-1β (v), and TNF-α (w) levels of db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. x, Representative H&E staining from colon tissue section. Scale bars, 100 μm. Representative images from three independent experiments with similar results are shown in a, t, x. Data in b-e, j, k, p-s, u-w are expressed as means ± s.e.m.; n = 5 mice. For box-and-whisker plots in f-i, l-o, the centre line denotes the median, the box bounds indicate the 25th and 75th percentiles, and the whiskers extend from the minimum to maximum values. P-values in b-s, u-w were calculated using one-way ANOVA followed by Tukey’s multiple comparisons test. NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001. Detailed statistics are provided in Supplementary Table 16.

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