Do Probiotics Improve the Health Status of Individuals with Diabetes Mellitus? A Review on Outcomes of Clinical Trials

Table 1

The anti-diabetic properties of probiotics supplementations: outcomes of randomized, double-blind, controlled clinical trials using human subjects.

Subjects	Intervention	Duration	Key observations	Health claim	Reference(s)
T2D patients	Soy milk with L. plantarum A7	8 weeks	↓ Urine albumin level	Improved the kidney function	[39]
			↓ Serum creatinine, IL-18, sialic acid levels Improved the GFR
DKD patients	Probiotic soy milk	8 weeks	↑ Reduced GSH, GPx, glutathione reductase	Improved the oxidative stress factors	[40]
T2D patients	Ecologic®Barrier	26 weeks	↓ Systemic inflammatory state, and inflammatory response	Improved the systemic inflammatory status	[15]
			↓ Endotoxin levels altered the gut microbiota
T2D patients	Ecologic®Barrier	12 weeks	↓ Waist-hip ratio Improved HOMA-IR	Improved HOMA-IR score	[16]
T2D patients	Ecologic®Barrier	6 months	↓ Endotoxin	Improved HOMA-IR score, and cardiometabolic profile	[17]
			↓ TG, TC, HOMA-IR
			↓ TNF-α, IL-6
			↓ C-reactive protein, resistin
			↑ Adiponectin
T2D patients	L. acidophilus L. casei, L. rhamnosus, L. bulgaricus, B. breve, B. longum, and Streptococcus thermophilus	8 weeks	↓ Fasting plasma glucose (FPG)	Improved the antioxidant status and mineral content	[18, 19]
			↑ Serum insulin, LDL level, HOMA-IR score Altered the hs-CRP value
			↑ Serum GSH level
			↑ Serum calcium level
			↓ Serum ALT
T2D patients	L. acidophilus, L. casei, L. rhamnosus, L. bulgaricus, B. breve, B. longum, S. thermophilus and FOS	6 weeks	↓ FPG	Improved the glycemic status	[20]
			↑ HDL No changes in TG, TC, insulin level, anthropometric values
T2D patients	L. sporogenes and inulin	6 weeks	↓ Serum insulin level, FPG, hs-CRP levels	Improved the metabolic status	[21]
			↑ Serum GSH level, uric acid
T2D patients	Yogurt containing L. acidophilus La5 and B. lactis Bb12	6 weeks	↓ TC, LDL	Improved the lipid profile and TAS	[41, 42]
			↓ TC: HDL, and LDL: HDL ratio
			↓ FPG, HbA1c, MDA
			↑ SOD, GPx, and TAS
			T2D patients			Yogurt containing L. acidophilus La5 and B. lactis Bb12	4 weeks	↓ FPG, HbA1c, TG	Improved the lipid profile and glycemic status	[43]
↓ LDL
T2D patients	L. acidophilus, L. casei, L. lactis, B. bifidum, B. longum, and B. infantis	12 weeks	↓ HbA1c, Fasting insulin level	Improved only HbA1c, fasting insulin level	[22]
T2D patients	L. reuteri ADR-1, and L. reuteri ADR-3	9 months	↓ HbA1c, Cholesterol level	Improved the fecal microbial composition	[23]
			↓ Blood pressure
			↑ Fecal Lactobacillus and Bifidobacterium load
T2D patients	L. reuteri DSM 17938	12 weeks	↑ Insulin sensitivity index	Improved insulin sensitivity	[24]
			↑ Serum deoxycholic acid
T2D patients	Symbiter	8 weeks	↓ HOMA-IR, HbA1c	Improved the insulin resistance	[25]
T2D patients	L. casei strain Shirota fermented milk	16 weeks	↓ Bacterial translocation	Reduced the bacterial translocation	[44]
			↑ Clostridium coccoides group
			↑ C. leptum subgroup, Lactobacillus species
T2D patients	Fermented milk (L. acidophilus La-5 and B. animalis subsp. lactis BB-12)	6 weeks	↓ HbA1c, fructosamine levels	Improved the glycemic control	[45]
			↓ TNF-α and resistin
			↓ TC, LDL
			↑ Fecal acetic acid
T2D patients	Lactobacillus spp., Bifidobacterium spp., S. thermophilus, and FOS	9 weeks	↓ FPG, HbA1c, BMI	Improved the glucose level and DM-associated parameters	[26]
			↓ Microalbuminuria
T2D patients	L. acidophilus, B. bifidum and FOS	30 days	↓ FPG, TC, TG, LDL	Improved the glycemic status	[27]
			↑ HDL
T2D patients with CHD	L. acidophilus, L. casei, B. bifidum and inulin	12 weeks	↓ FPG, insulin level, HOMA-β cell function	Improved the insulin metabolism	[28]
			↑ Insulin sensitivity index, HDL
T2D patients	L. salivarius UBLS, L. casei UBLC42, L. plantarum UBLP40, L. acidophilus UBLA34, B. breve UBBR01, Bacillus coagulans Unique‑IS2, and FOS	12 weeks	↓ FPG, postprandial blood sugar, insulin level, HOMA-IR	Improved the HRQL	[29]
GDM patients	L. acidophilus LA-5, Bifidobacterium BB-12, S. thermophilus STY-31, and L. delbrueckii bulgaricus LBY-27	8 weeks	↓ Weight gain	Influenced the weight gain and glucose metabolism	[31]
			↓ FPG
			↓ Insulin resistance index
			↑ Insulin sensitivity index
GDM patients	L. acidophilus LA-5, Bifidobacterium BB-12, S. thermophilus STY-31, and L. delbrueckii bulgaricus LBY-27	8 weeks	↓ TNF-α	Improved inflammation and antioxidant status	[32]
			↓ hs-CRP value
			↓ IL-6, MDA, uric acid
			↑ Glutathione reductase, SOD, TAS
GDM patients	VSL#3	8 weeks	No change in FPG, HbA1c values, and insulin level	Improved the inflammatory markers	[33]
			↓ IL-6, hs-CRP, TNF-α
GDM patients	L. acidophilusL. casei and B. bifidum	6 weeks	↓ FPG, insulin level, HOMA-IR, HOMA-β-cell function	Glycemic control	[34]
			↓ TG, VLDL
			↑ Insulin sensitivity
GDM patients	Infloran®	4 weeks	↓ FPG, fasting insulin level, HOMA-IR	Glycemic control	[35]
GDM patients	L. rhamnosus HN001	—	↓ FPG	Reduced the GDM prevalence	[36]
			↓ Relative rate of GDM
Pre-diabetic patients	Probiotics (L. acidophilus, B. lactis, B. bifidum, and B. longum); Synbiotic (probiotics + inulin)	24 weeks	↓ FPG, fasting insulin level, HOMA-IR, HbA1c	Glycemic improvement	[37]
			↑ QUICKI score
Pre-diabetic patients	Probiotics (L. acidophilus, B. lactis, B. bifidum, and B. longum); Synbiotic (probiotics + inulin)	24 weeks	↓ Hyperglycemia, hypertension	Improved the metabolic syndrome	[38]
			↓ Metabolic syndrome associated parameters

T2D: Type 2 diabetes; DKD: Diabetic kidney disease; IL-18: Interleukin-18; GFR: Glomerular filtration rate; HOMA: Homeostasis model of assessment; HOMA-IR: Homeostasis model of assessment-insulin resistance; VLDL: Very low-density lipoprotein LDL: Low-density lipoprotein; HDL: High-density lipoprotein; hs-CRP: High-sensitivity C-reactive protein, GSH: Glutathione; TG: Triglycerides; ALT: Alanine aminotransferase; GDM: Gestational diabetes mellitus; DM: Diabetes mellitus; HbA1c: Hemoglobin A1c; BMI: Body mass index; TC: Total cholesterol; SOD: Superoxide dismutase; GPx: Glutathione peroxidase; TAS: Total antioxidant status; MDA: Malondialdehyde; TNF-α: Tumor necrosis factor-α; QUICKI: Quantitative insulin sensitivity check index; CHD: Coronary heart disease; HRQL: Health‑related quality of life; FOS: Fructooligosaccharide.