Table 2.

Nutraceutical agents influencing the gut microbiota in experimental and clinical studies.

Nutraceutical Agent	Type of Clinical Study/Type of Diabetes Mellitus	Effects	References
Prebiotics
Inulin	Experimental study (rats with streptozotocin-induced diabetes)	Decreased fasting blood glucose levels Increased serum GLP-1 level Decreased serum IL-6 level Decreased abundance of Desulfovibrio Increased Lactobacillus, Lachnospiraceae, Phascolarctobacterium, and Bacteroides	[120]
Prebiotic: oligofructose-enriched inulin	Clinical study/T1DM	Decreased intestinal permeability Increased Bifidobacterium and Actinobacteria Increased C-peptide	[121]
Probiotics
Lactobacillus G15 and Q14, separated from Chinese traditional fermented diary food	Experimental study (rats with streptozotocin induced diabetes)	Improved glucose intolerance Reduced serum lipid levels Decrease IL-1β, IL-8, and IL-6 levels Increased the concentration of GLP-1 and PYY Reduced intestinal mucosal permeability	[122]
Bifidobacterium spp.	Experimental study (mice with streptozotocin induced diabetes)	Decreased blood glucose level Reduced MCP-1 and IL-6 mRNA levels in adipose tissue Increased the levels of IR-β, IRS-1, and Akt proteins	[123]
Lactobacillus gasseri BNR17	Experimental study (C57BL/KS/J db/db mice)	Decreased fasting and post-prandial blood glucose levels Decreased HbA1c	[124]
Lactobacillus spp.	Experimental study (rats with streptozotocin induced diabetes)	Decreased oxidative damage Inhibited the depletion of insulin	[125]
Lactobacillus spp.	Experimental study (high-fat diet mice)	Decreased fasting blood glucose levels No impact on insulin levels and lipid profile	[126]
Lactobacillus plantarum	Experimental study (rats with alloxan-induced diabetes)	Improves immunological parameters Protected the pancreatic, renal and hepatic tissues Reduced serum triglycerides and LDL cholesterol and increased the levels of HDL cholesterol	[127]
Lactobacillus spp.	Experimental study (rats with streptozotocin induced T1DM)	Improved glucose metabolism (HbA1c, fasting glucose, and insulin levels) Improved the inflammatory and oxidative stress status Improved the lipid profile	[128]
Bifidobacterium spp.	Experimental study (mice with streptozotocin induced diabetes)	Reduced blood glucose levels Decreased insulin resistance Induced adiponectin, MCP-1 and IL-6 expression	[123]
Lactobacillus paracasei	Experimental study (rats with streptozotocin-induced diabetes)	Decreased blood glucose levels, insulin resistance, and HbA1c Decreased glucagon and leptin levels Improved dyslipidemia and oxidative stress status	[129]
Bifidobacterium bifidum, Lactobacillus casei, Lactobacillus acidophilus	Clinical study (adults with T2DM)	Decreased fasting blood glucose, decreased HOMA-IR Increased HDL cholesterol levels Decreased serum hs-CRP Increased plasma TAC, increased GSH level	[130]
L. reuteri DSM 17938 (high dose)	Clinical study (adults with T2DM)	Improve the insulin sensitivity index Improved the serum deoxycholic acid Did not significantly improve HbA1c	[131]
Lactobacillus spp.	Clinical study/T2DM	Decreased insulin resistance Decreased triglycerides, IL-6 and MDA levels	[132]
Lactobacillus spp. and Bifidobacterium spp.	Clinical study/T2DM	Decreased fasting blood glucose levels and HbA1c Improved antioxidant status No changes in insulin concentration	[133]
Lactobacillus, Bifidobacterium, Lactococcus and Propionibacterium spp.	Clinical study/T2DM	Decreased HbA1c Decreased TNF-α and IL-1β Decreased insulin resistance	[134]
Lactobacillus spp.	Clinical study/T2DM	Decreased HbA1c and serum cholesterol levels Decreased blood pressure Reduced IL-1β Increased Bifidobacterium spp.	[135]
Lactobacillus and Bifidobacterium spp.	Clinical study/T2DM	Decreased HbA1c Improved fasting insulin levels	[136]
Lactobacillus rhamnosus	Clinical study/GDM	Lowered the relative rates of GDM Significantly lowered the prevalence of GDM	[137]
Symbiotics
Selenium enhanced Bifidobacterium spp.	Experimental study (mice with streptozotocin induced diabetes)	Reduced levels of fasting glucose, HbA1c, leptin, and insulin Improved glucose tolerance and lipid profile Protected against liver and pancreatic impairment	[138]
Lactobacillus sporogenes, inulin as prebiotic, beta-carotene	Clinical study/T2DM	Significantly decreased serum insulin, HOMA-IR, HOMA-B, serum triglycerides elevated plasma NO, and GSH levels	[139]
Lactobacillus, Bifidobacterium species, S. thermophilus, and fructo-oligosaccharide)	Clinical study/T2DM	Decreased fasting blood glucose Decreased hemoglobin A1c Did not significantly influence lipid profile	[140]
Lactobacillus spp., Bifidobacterium spp. and oligofructose shake	Clinical study/T2DM	No significant decrease in total cholesterol and triglycerides Increased HDL Decreased fasting blood glucose levels	[141]
Lactobacillus spp., Bifidobacterium spp. Streptococcus spp. and fructo-oligosaccharide	Clinical study/T2DM	Decreased fasting blood glucose levels Increased insulin levels Increased LDL levels Increased total GSH levels	[142]
Other Nutraceuticals
Caffeic acid-rich fraction of Prunella vulgaris L.	Experimental study (mice with alloxan-induced diabetes)	Reduced blood glucose levels and HbA1c Improved antioxidant activity Increased insulin levels	[143]
Thymus marshallianus	Experimental study (rats with streptozotocin-induced diabetes)	Reduced blood glucose levels Improved oxidative stress status Improved neurological functions	[144]

Akt, protein kinase B; CRP, C-reactive protein; DM, diabetes mellitus; GDM, gestational diabetes mellitus; GSH, glutathione; GLP-1, glucagon-like peptide-1; HOMA-IR/-B, homeostatic model assessment-insulin resistance/beta-cell function; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; IL, interleukin; IR-β, insulin receptor β; IRS-1, Insulin receptor substrate 1; LDL, low-density lipoprotein; MCP-1, monocyte chemoattractant protein 1; MDA, malondialdehyde; NO, nitric oxide; PYY, peptide YY; TAC, total antioxidant capacity; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TNF, tumor necrosis factor.