Table 2.
Summary of major animal studies of probiotic interventions, their mechanism of action and their outcomes related to T1D.
| Name of Probiotic strains | Study type | Probiotic type and dose | Duration of intervention | Mechanism of action | Outcomes | Reference | Year |
|---|---|---|---|---|---|---|---|
| VSL#3 (VSL Pharmaceuticals, Ft Lauderdale, FL, USA): 3 × 1011 CFU /g of bifidobacteria (B. longum, B. infantis, and B. breve), lactobacilli (L. acidophilus, L. casei, L. delbrueckii subsp. L. bulgaricus, and L. plantarum) and Streptococcus salivarius subsp. thermophilus. | NOD mice | Three times a week of 3 mg/mouse, re-suspended in 100 μl PBS | 28 weeks (from 4 to 32 weeks of age) | - Increases production of IL-10 from Peyer's patches and the spleen and with increase of IL-10 expression in the pancreas - Modulates GALT |
- VSL#3 prevented autoimmune diabetes development in NOD mice - VSL#3 protected mice and induced immunomodulation by a reduction in insulitis severity |
(115) | 2005 |
| Lactobacillus johnsonii N6.2 | T1D in BB-DP Rats | 1 × 108 CFU per animal/day | 21 day | - Changes in the native microbiota, host mucosal proteins, and host oxidative stress response - Decreases oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat) - Decreases of the level of the pro-inflammatory cytokine IFNγ - Increases of the level of the tight junction protein claudin |
- Delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. | (116) | 2010 |
| Lactobacillus johnsonii N6.2-Mediated | T1D in BB-DP Rats | 1 × 108 CFU/day through oral gavage | - BBDP rats received oral treatments daily until sacrifice at diabetes onset, or the culmination of the experiment at 140 day | - Diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes - Cytokines IL-6 and IL-23, respectively, were significantly higher within the mesenteric lymph nodes of LjN6.2-fed BBDP. |
- Confirms resistance of T1D and the results published in (117) | (114) | 2011 |
| Lactococcus lactis | NOD mice | Not mentioned | Not mentioned | - Increases the frequencies of local Tregs accumulated in the pancreatic islets, - Suppresses immune response in an autoantigen-specific way - Preserves functional pancreatic islets and reduces in insulitis severity |
- Reversal of autoimmune diabetes by restoration of antigen-specific tolerance: - Treatment strategy for 1TD in human |
(117) | 2012 |
| Lactobacillus plantarum TN627 | Alloxan-induced diabetes in rats | 0.9 × 109 CFU/ml/day | Not mentioned | - Improves the immunological parameters, - Protects the pancreatic tissues, and reduce the pancreatic and plasmatic α-amylase activities and level of plasma glucose in the treated as compared to the control group of rats - Reduces the pancreatic and plasmatic lipase activities and serum triglyceride and LDL-cholesterol rates - Increases the level of HDL-Cholesterol - Protects the liver and kidney functions by decreasing in serum aspartate transaminase, alanine transaminase, lactate dehydrogenase, and gamma-glutamyl transpeptidase activities, as well as creatinine and urea contents. |
- Exhibits attractive in vivo antidiabetic effects that may be helpful in preventing diabetic complications in adult rats | (118) | 2013 |
| Bacterial LPS or Zymosan | NOD mice | 25 μg/mouse/day in PBS | 25 μg/mouse/day in PBS on days 1, 3, 5, 16, 18, and 20 after 12 weeks-old mice | - TLR2 and Dectin 1 engagement by zymosan promotes regulatory T-cell (Treg) responses against the pancreatic β-cell–specific antigen (Ag) - Zymosan induces a mixture of pro - and anti-inflammatory factors and Tregs, both in vitro and in vivo - Increased frequencies of IL-10–, IL-17–, IL-4–, and Foxp3-positive T cells, especially in the pancreatic lymph node |
- Zymosan can be used as an immune regulatory adjuvant for modulating the T-cell response to pancreatic β-cell-Ag - Reverses early-stage hyperglycemia in T1D |
(119) | 2015 |
| Bifidobacterium spp. | STZ-induced C57BL/6 diabetic mice | Not mentioned | 5 weeks | - Reduces the blood glucose levels significantly - Increases the protein expressions of insulin receptor beta, insulin receptor substrate 1, protein kinase B (Akt/PKB), IKKα, and IκBα - Decreases both macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) expression |
- Promote the recovery of β-cells of pancreas or increase insulin sensitivity in mice by enhancing the function of the insulin signaling pathway may be the promising bacteria for treating diabetes | (120) | 2015 |
| Lactobacillus reuteri | STZ-induced C57BL/6 diabetic mice | 109 CFU / 0.3 ml directly into the stomach of mice 3 times per week | 4 weeks | - Develops anti-inflammatory property by inhibiting osteoblast TNF-α signaling - Prevents TNF-α-mediated suppression of Wnt10b and osteoblast maturation markers |
- Blocks the loss of bones open new avenues for use of probiotics to benefit the bone. | (121) | 2015 |
| Lactobacillus kefiranofaciens M and Lactobacillus kefiri K | STZ-induced C57BL/6 diabetic mice | 1 × 108 CFU per day | 8 weeks | - Stimulates the secretion of GLP-1, inhibiting the proinflammatory and inflammatory cytokines, elevating the production of IL-10, and modifying the intestinal microbiota - Decreases of the level of the pro-inflammatory cytokine TNFa and TH1 |
- Potential ability of enhancing GLP-1 to mitigate the progression of type 1 diabetes in vitro and in vivo | (122) | 2015 |
| Oral Probiotic VSL#3 | NOD mice | VSL#3 was administered through oral gavage three times a week | 6 weeks (starting at 4 weeks until 20 weeks of age) | - Inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO) and IL-33 - Promotes differentiation of tolerogenic CD103+ DCs and reduces differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity within the pancreatic lymph nodes (PLN) - Reduces the Teff/Treg cell balance in the gut mucosa and PLN |
- Prevents autoimmune diabetes by modulating microbiota | (123) | 2016 |
| Lactobacillus brevis KLDS 1.0727 and KLDS 1.0373 | STZ-induced C57BL/6 T1D mice | Not mentioned | 4 weeks | - Capability of KLDS 1.0727 and KLDS 1.0373 strains as gad gene carriers to overexpress GABA significant effect on glucose level reduction in blood or insulin in plasma | - Inhibits the development of T1D in diabetic mice model | (124) | 2018 |
| Probiotic fermented milk with: Lactobacillus rhamnosus MTCC: 5957, Lactobacillus rhamnosus MTCC: 5897 isolated from dairy product (isolated from household curd) and Lactobacillus fermentum MTCC isolated from breast-fed human infant feces | STZ-induced diabetic rat | Not mentioned | 6 weeks | - Decreases in the levels of blood glucose and HbA1c - Increases in the body weight, serum insulin, HDL-C levels in diabetic rats - Decreases in the inflammation, oxidative stress, and gluconeogenesis |
- Can be useful for the complementary treatment strategies of diabetes and its associated complications | (125) | 2018 |