Table 1.
Summary of major animal studies of probiotic and prebiotic interventions and their findings related to T1D-associated features and outcomes.
| Probiotics/Prebiotics | Model Type | Mechanism of Action | Major Findings | References |
|---|---|---|---|---|
| Oral Probiotics VSL#3 (Bifidobacteriaceae, Lactobacillaceae, Streptococcus thermophilus) | NOD mice | - Generates more pro-tolerogenic components of inflammasome like indoleamine 2,3-dioxygenase (IDO) and IL-33. - Reduces the synthesis of inflammatory cytokines like IL-1β. - Promotes CD103+ differentiation. - Reduces Teff/Treg cell ratios within the gut mucosa, MLNs and PLNs. |
- Modification of gut microbial environment. - Modulating T1D pathogenesis. |
[73] |
| Bacterial LPS or Zymosan | NOD mice | - Produces synergetic innate immune response through TLR2 and Dectin-1 signaling. - Eliminates inflammatory immune cells and suppresses autoimmunity. - Triggers the secretion of immune regulatory factors like IL-10, TGF-β1, IL-2 and Raldh1A2. - Increases the numbers of Foxp3+CD4+ T cells in the PLN but not in spleen. |
- Used as an immune regulatory adjuvant for promoting β-cell antigen-specific immune modulation. - Reverses the early stages of hyperglycemia in T1D. |
[47] |
| Lactobacillus brevis KLDS 1.0727 and KLDS 1.0373 | STZ-induced C57BL/6 T1D mice | - High GABA generating capacity due to the gad gene. - Significant effect in lowering the blood glucose level or insulin in plasma. |
- Inhibits the development of T1D in diabetic mice model. | [62] |
| PFM with 1% of Lactobacillus species | STZ-induced albino wistar T1D rats | - Significant decrease in the expression of hepatic gluconeogenesis gene like Glucose-6-phosphatase (G6Pase) and Phosphoenol pyruvate carboxykinase (PEPCK) in the liver. - Significant reduction in serum inflammatory cytokines like IL-6 and TNF-α -Decrease in HbA1c, blood glucose level and serum lipid profile. -Significant increase in the serum insulin level. |
- Increases insulin level with significant reduction in blood glucose level. - Improvement in glucose metabolism -Decrease in inflammation, oxidative stress and hepatic gluconeogenesis. |
[83] |
| HMOS Prebiotic | NOD Mice | - Increases SCFA concentration in the gut. - Limits autoimmune T-cells and increases the Treg cells. - Induces tolerogenic DC phonotype by induction of MHC II and increases the expression of inhibitory molecules such as PD-L1 and OX40-L. -Increased butyrate production promoting mucin synthesis. - Improves intestinal barrier integrity. -Reduced pancreatic islet destruction by regulating the immune system. |
- Modulation and maintaining the α- and β-diversity of the fecal microbiota. - Changes the direct shape of the pancreatic environment, resulting in less insulitis. - Helps in protection against T1D. |
[102] |
| Dietary Resistant starch | STZ-induced T1D Sprague-Dawley rats | - Influences the secretion of GLP-1 and PYY hormones. - Proliferation of β-cell and insulin synthesis. - Provides nephron-protection. - No effect on blood glucose level and Vitamin D balance. |
- Develops normalized growth pattern in T1D. | [104] |
| CARF extracted from PV | Alloxan-induced T1D Swiss Webster mice | -Decreases α-amylase and α-glucosidase activity. - Reduces HbA1c level. - Elevates serum insulin level. - Increases antioxidant enzyme level. |
- Poses anti-diabetogenic, anti-nociceptive and hypoanalgesic properties as therapeutic agents against T1D. | [64] |
| Prebiotic oligofructose | High fat diet induced diabetic C57b16/J mice | -Increases Bifidobacteria number by modifying gut microbiota. - Decreases endotoxemia. -Improves glucose tolerance and regulates glucose-induced insulin secretion. -Increases colonic GLP-1 secretion. |
-Pathophysiological regulation of endotoxemia. - Sets the tone of inflammation, glucose tolerance and insulin secretion. |
[101] |
| Oral transfer prebiotic Lactobacillus johnsonii N6.2-Mediated | KRV virus induced-BBDP rat | - TH17 lymphocyte biasness within the gut-draining MLN. - Cytokines, like IL-6 and IL-23, were responsible for induction and sustenance of TH17 cells was higher. - Retention of TH17 differentiation state that may prevent T-cell conversion to the diabetogenic phenotype. |
- Confirms resistance to T1D. | [65] |
| Probiotic Bifidobacterium spp. | STZ-induced C57BL/6J diabetic mice | - Significant reduction in blood glucose level. - Increases the protein expression of insulin receptor β, insulin receptor substrate 1, (Akt/PKB), IKKα, IκBα. - Decreases the macrophage chemoattractant protein-1 and IL-6 expression. |
- Responsible for treating diabetes. | [72] |
| Lactobacillus reuteri | STZ-induced C57BL/6 diabetic mice | - Development of anti-inflammatory property by inhibiting osteoblast TNF-α signaling. - TNF-α modulates the Wnt10b expression in T1D. |
- Use of probiotic to benefit bones in T1D patients. | [74] |
| Lactococcus lactis | NOD Mice | - Increases the frequency of local Tregs in the pancreatic islet. - Suppresses immune response in an autoantigen-specific way. - Preserves functional β-cell mass and reduces insulitis. - Secretion of human pro-insulin and IL-10 can stably revert autoimmune diabetes. - Induced Ag-specific Foxp3+ Tregs that prevent diabetes transfer. |
- Treatment strategy for T1D in humans. | [76] |
| Lactobacillus kefiranofaciens and Lactobacillus kefiri | STZ-induced C57BL/6 diabetic mice | - Level of IL-10 significantly raised in pancreas. - Increased IL-10 inhibits the secretion of pro-inflammatory cytokines, like TNF-α and TH1 (also IL-1β, IL-2, IL-6). |
- Potential ability to stimulate the release of GLP-1. | [78] |
| Bifibobacteria, lactobacilli and Streptococcus salivarius subs. | NOD mice | - Decreases the rate of β cell destruction. - Increases the production of IL-10 from PPs, pancreas and spleen. - Modulates GALT. |
-Prevention of autoimmune diabetes. -Induces immunomodulation by a reduction in insulitis severity. |
[79] |
| Lactobacillus johnsonii N6.2 | T1D BBDP rats | - Changes in the native gut microbiota. - Induced changes in host mucosal protein and oxidative stress response. - Decreases oxidative response protein in the intestinal mucosa. - Decreases pro-inflammatory cytokines, like IFN-γ. - Higher expression of tight junction proteins, like claudin. |
- Delays or inhibits the occurrence of T1D. | [82] |
| Lactobacillus plantarum TN627 | Alloxan induced-diabetic rat | - Improved the immunological parameters of the pancreas. - Reduced the pancreatic and plasmatic α-amylase activity as well as blood glucose level. - Decreased the pancreatic and plasmatic lipase activity, serum triglyceride and LDL-cholesterol rate. - Increases the HDL-cholesterol rate. |
- Helpful in preventing diabetic complications in the adult rat. | [84] |
| Low antigen, hydrolyzed casein-based diet | LEW.1AR1-iddm Rat model | - Increased immunoregulatory capacity and gut immune deficits. - Decreased expression of CD3+ T-cells, CD163+ M2 macrophages and Foxp3+ cells in jejunum. - Decrease in CD4+ Foxp3+ regulatory T-cells in PLNs. - IFN-γ expression increase in MLNs. |
- Protection against T1D. | [105] |
|
Bifidobacterium animalis ssp. lactis 420 (B420) and Metformin |
Ketogenic diet-induced C57Bl/6J diabetic mice | - Increases ileum GLP-1 concentration. - Increases the amount of insulin released from pancreatic β-cells. - Significantly decreases the glycemic response and plasma glucose concentration. |
- Improves glucose metabolism and insulin secretion. - Improves the efficacy of metformin. |
[107] |
| Wheat Flour | NOD mice | - Lacks the epitopes linked with T1D. -Reduction in the level of pro-inflammatory cytokines, like IFN-γ. -Increase in the level of anti-inflammatory cytokine IL-10. |
- Reducing the incidence of T1D. | [106] |
| Systemic GABA therapy | STZ-induced C57/BL6 T1D mice | - Increases klotho (anti-aging agent) level expression in serum, pancreatic Islet of Langerhans and kidneys. - Klotho stimulates pancreatic β-cells survival and proliferation. - Increases insulin secretion. - Klotho blocks NF-κB activation by interfering with its nuclear translocation. - Suppresses autoimmune responses. |
- Important implications for the treatment of T1D. | [108] |
| Dietary fibers | NOD mice | - Increases CD25+Foxp3+CD4+ Treg and decreases IL17A+CD4+Th17 cells. - Changes the cytokine production profile in the pancreas, spleen and colon. - Enhances tight junction proteins (claudin-2, occludin) and SCFAs. - Enhances Firmicutes/Bacteroidetes ratio as well as Ruminococcaceae and Lactobacilli. |
- Modulates T-cell response. - Modulates gut-pancreatic immunity. - Delays the development of T1D. |
[99] |
Abbreviations: Ag: antigen; Akt/PKB: protein kinase B; BBDP: bio-breeding diabetic pathogen; DC: dendritic cell; GABA: gamma-aminobutyric acid; GALT: gut-associated lymphatic tissue; GLP-1: glucagon-like peptide-1; HDL-cholesterol: high-density lipoprotein-cholesterol; HbA1c: hemoglobin A1c; HMOS: human milk oligosaccharide; IκKα: IκB kinase alpha; IκBα: Nuclear factor-kappa B inhibitor alpha; IL: interleukin; KRV: Kilham rat virus; LDL-cholesterol: low-density lipoprotein-cholesterol; LPS: lipopolysaccharide; MHC: major histocompatibility complex; MLN: mesenteric lymph node; NOD: non-obese diabetic; PLN: pancreatic lymph node; PP: Peyer’s patches; PYY: peptide YY; SCFA: short-chain fatty acid; STZ: Streptozotocin; T1D: type-1 diabetes; Teff: effector T-cell; TGF: transforming growth factor; Th17 cell: T-helper cell 17; TLR: toll-like receptor; TNF: tumor necrosis factor; Treg: regulatory T-cell.