Molecular Microbiology Research 2024, Vol.14, No.1, 10-19 http://microbescipublisher.com/index.php/mmr 16 3.3.1 Berberine and probiotic combination therapy as an effective strategy for improving postprandial hyperlipidemia in type 2 diabetes patients Research shows that non-fasting lipid abnormalities are associated with cardiovascular disease risk and are equally important as fasting lipid abnormalities. In a randomized, placebo-controlled, multicenter clinical trial, the effect of combined therapy with probiotics and berberine on lipid abnormalities in newly diagnosed T2D patients was evaluated. This treatment regimen was found to effectively reduce postprandial lipid levels in T2D patients. Compared to berberine alone, the addition of probiotics did not show additional effects in improving postprandial triglycerides. However, the effect of combination therapy remained significant after excluding patients taking lipid-lowering medications. This indicates that berberine effectively lowers fasting lipid levels but has limited impact on postprandial cholesterol levels, which may require synergistic action with probiotics (Maifeld et al., 2021). Further research revealed the specific mechanisms by which combination therapy affects lipid metabolism through liquid chromatography/mass spectrometry analysis. The results showed that combination therapy influenced 20 out of 31 postprandial lipid metabolites, including long-chain to medium-chain fatty acids, acylcarnitines, and various glycerophospholipids. Changes in these key lipid metabolites were closely associated with improvements in low-density lipoprotein cholesterol and total cholesterol levels, as well as improvements in triglycerides and glycemic indices. This suggests that the reduction of various postprandial free fatty acids and phospholipids after combination therapy may contribute to the overall reduction in lipid levels. This study demonstrates the effectiveness of oral probiotic and berberine combination therapy in improving lipid abnormalities in newly diagnosed T2D patients, providing a new microbiome-related drug strategy for lipid management in T2D patients (https://international.biocloud.net/zh/article/detail/34923903). 3.3.2 Intestinal antimicrobial peptides shape protective gut microbiota in neonates to counteract pancreatic autoimmunity Alterations in the gut microbiota are associated with the development of autoimmune type 1 diabetes (T1D), as demonstrated in both human and non-obese diabetic (NOD) mouse models. However, how dysbiosis in the gut ecosystem arises and promotes autoimmune responses remains a lingering question. Research investigates whether early events influencing the intestinal homeostasis of neonatal NOD mice can explain the development of pancreatic autoimmunity in humans. Liang et al. (2021) analyzed the transcriptome and colonic microbiota between neonatal NOD mice and non-autoimmune strains. A seminal defect was identified in the intestinal homeostasis of neonatal NOD mice, elucidating the mechanistic link between this defect and adult diabetic responses. Liang et al. (2021) determined defective expression of cathelicidin-related antimicrobial peptide (CRAMP) in the colon of neonatal NOD mice, resulting in dysbiosis. Dysbiosis stimulates colonic epithelial cells to produce type I interferon, which pathologically imprints the neonate's local immune system. This pathological immune imprint later promotes adult pancreatic autoimmunity and diabetes development. Restoration of colonic homeostasis, cessation of diabetic responses, and prevention of autoimmune diabetes were achieved by local CRAMP treatment or probiotic supplementation to enhance colonic CRAMP expression in neonatal NOD mice (Liang et al., 2021). The study identified whether defects in colonic expression of CRAMP antimicrobial peptide lead to dysbiosis, thereby causing pancreatic autoimmunity. Therefore, manipulation of intestinal antimicrobial peptides may be considered a relevant therapeutic approach for preventing autoimmune diabetes in high-risk children (Figure 4). 3.3.3 Dietary supplements based on metabolites in type 1 diabetes patients are associated with microbiota and immune regulation Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and can prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates loss of beneficial bacteria, which is often associated with chronic autoimmune and inflammatory diseases, including T1D
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