**2. Probiotic interventions to ameliorate T1DM**

Probiotics may, thus, be useful in T1DM prevention and management. By altering the gut microbiota, certain probiotic strains exhibit a positive impact on host health by boosting the synthesis of advantageous metabolites [53]. Additionally, by activating free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3), which are involved in the regulation of the immune system and the pathogenesis of autoimmune diseases like T1DM, the administration of probiotic strains may increase the production of SCFAs (such as butyrate) and thereby balance the intestinal cellular homeostasis [54]. Additionally, intestinal L-cells' ability to produce glucagon-like peptide-1 (GLP-1) might be improved by the activation of FFAR2/3 by SCFAs. The hormone GLP-1 is known as the "incretin effect" because it promotes the release of insulin from pancreatic beta-cells, lowering blood sugar levels [55, 56]. These findings show how probiotics may prevent or manage T1DM by preserving or re-establishing the gut microbiota-immune axis' equilibrium. **Figure 2** shows an overview of potential mechanisms of probiotics against type 1 diabetes.

### **2.1 Animal studies**

*Lactobacillus brevis* strains protect mice (streptozotocin [STZ]-induced T1DM) and lower blood glucose levels via the action of gamma-aminobutyric acid (GABA) [57]. It has been shown that probiotic strains from the families *Bifidobacteriaceae* and *Lactobacillaceae* and the genus *Streptococcus thermophilus* reduce intestinal

*Probiotics in the Management of Diabetes DOI: http://dx.doi.org/10.5772/intechopen.110338*

**Figure 2.** *Potential mechanisms of probiotics against type 1 diabetes.*

inflammation, alleviate T1DM, and maintain gut immunological homeostasis by blocking IL-1 expression in nonobese diabetic (NOD) mice [58]. The feeding of a *Lactobacillus lactis* strain has also been demonstrated to have preventative benefits against T1DM development in NOD mice by the activation of the production of anti-inflammatory cytokines. Interestingly, the combination of the *L. lactis* strain with modest dosages of anti-CD3 boosted the production of IL-10. The intervention also led to the formation of antigen-specific Foxp3+ Tregs, which preserves pancreatic islets [59, 60]. *Bifidobacterium* species change the cytokine secretion pattern in gut-associated lymphatic tissue (GALT) from a proinflammatory condition to an anti-inflammatory. Controlling the preservation of the variety of B-cells and lowering insulitis reduced the likelihood of developing an islet-specific autoimmune disease and offered protection against autoimmune T1DM [61]. **Table 1** shows an overview of important studies demonstrating the effect of probiotics on an animal model with type 1 diabetes mellitus.

Biobreeding diabetes resistant (BBDR) rats are more likely to develop T1DM when exposed to Kilham rat virus (KRV) infectious disease [67]. Similar results have also been seen in LEW.1WR1 rats that have had viral infections; these animals acquire autoimmune T1DM as a result of the infection of their cells. It has been shown experimentally that the oral administration of the *Lactobacillus johnsonii* strain develops resistance to the onset of T1DM in BBDR rats [67]. Consequently, *L. johnsonii* was linked to TH17 lymphatic cell predilection inside the mesenteric lymph nodes (MLNs) and might lower the incidence of T1DM in the bio-breeding diabetes-prone (BBDP) rat model. Increasing the level of the intestinal tight-junction protein claudin, *L. johnsonii*, also reduced the likelihood of developing T1DM [66]. In another experiment, probiotic-fermented milk was fed to diabetic rats induced by STZ. Consuming probiotic-fermented milk also reduced oxidative stress, inflammation, blood sugar



### **Table 1.**

*Overview of important studies demonstrating the effect of probiotics on an animal model with type 1 diabetes mellitus.*

levels, and the rate of gluconeogenesis [62]. Another investigation employing probiotic strain *Lactobacillus plantarum* in diabetic rats concluded that taking probiotics significantly decreased the serum α-amylase's activity, favoring the glycemic index mechanism by limiting the digestion and hydrolysis of carbohydrates [68].

### **2.2 Human studies**

Early exposure to probiotic supplements may reduce the incidence of islet-cell autoimmunity in relation to the increased risk of T1DM [69–71]. Additionally, probiotic usage has been linked to improved glucose control, increased GLP-1 production, and decreased TLR4 signaling in T1DM adults [72–74]. T1DM occurrences have reduced as a result of these modifications. Children with T1DM may benefit from taking *Lactobacillus rhamnosus* and *Bifidobacterium lactis* at a dosage of 109 colony-forming units (CFUs) once a day for six months regulates gut microbiota disturbances. Results indicated the modification of immune cells in a positive way and maintaining the quantity and proliferation of pancreatic β-cells [75]. Additionally, it has been suggested that adult human subjects consuming *Lactobacillus johnsonii* N6.2 (108 CFUs) in one capsule per day for eight weeks can control the natural killer cells and infiltration of monocytes. These modifications may help to prevent the development of T1DM. Furthermore, probiotic therapy has been linked to an increase in TH17 and TH1/TH17 cells. However, the probiotics-treated group showed a substantial rise in IgA concentration as compared to the placebo group [71]. **Table 2** shows an overview of important studies demonstrating the effect of probiotics on human subjects with type 1 diabetes mellitus.

By using probiotics products, T1DM adult patients might improve their glycemic control and manage symptoms associated with metabolic syndromes, such as hypertension, elevated level of triglyceride, and decreased HDL levels. These findings together imply that probiotic intake may lower the likelihood of T1DM progression. Other research on young children with a genetic risk of T1DM consumed a probiotic strain during the first two years of life and the risk of the onset of islet autoimmunity


### **Table 2.**

*Overview of important studies demonstrating the effect of probiotics on human subjects with type 1 diabetes mellitus.*

and progression of T1DM was increased [77]. This suggests that all probiotic strains do not have the same effects, although the cause of the results from these studies is still unknown.
