**3.1 Animal model study**

Probiotics have been proven in studies to reduce insulin resistance (IR) in diabetic animal models (see **Table 3**). Probiotics like *Lactobacillus* spp. and *Bifidobacterium* spp. have been widely studied in diabetic animal models for their biological effects on glucose intolerance and insulin resistance (IR). *Lactobacillus plantarum* was given to the rats (which consume high-fat-diet [HFD]- and STZ-induced diabetes). It has been observed that *L. plantarum* reduces pancreatic beta-cell dysfunction, systemic inflammation, and insulin resistance [79]. *L. plantarum* reduced the weight and relieved IR in mice fed on the HFD [80]. In mice with diabetes generated by HFD, therapy with *Lactobacillus fermentum* has been demonstrated to reduce IR and stop the progression of diabetes [81]. The injection of *Lactobacillus paracasei* TD062 increased the insulin signaling pathway and improved glucose homeostasis, delaying the onset of T2DM [82]. In STZ-induced diabetic rats, a multiprobiotic formula, including *Lactobacillus reuteri,* 


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


### **Table 3.**

*Overview of important studies demonstrating the effect of probiotics on an animal model with type 2 diabetes mellitus.*

*Lactobacillus crispatus,* and *Bacillus subtilis*, was studied. This research revealed that the daily consumption of probiotics may reduce glucose intolerance and increase insulin production [83]. By lowering fasting blood glucose (FBG), the oral glucose tolerance test (OGTT), and the HbA1c indices and increasing GLP-1 secretion, a composite probiotic made up of 10 *Lactobacillus* strains and four yeast strains were reported to improve T2DM in db/db mice [89]. Nano-selenium-enriched *Bifidobacterium longum* reduced the renal complication of T2DM in STZ-induced diabetes rats [84]. *B. longum* DD98 reduced the fasting blood glucose and HbA1c in HFD- and STZ-induced diabetic mice [90]. In diabetic rats caused by HFD and STZ, *Bifidobacterium animalis* administration increased oral glucose tolerance test and homeostatic model assessment for insulin resistance (HOMA-IR) indices and decreased proinflammatory cytokines [91].

### **3.2 Human studies**

Sabico et al. examined the effects of consuming 1010 CFU/day of a multistrain probiotic regarding metabolic endotoxemia levels and cardiometabolic parameters in adult patients recently diagnosed with T2DM. It has been found that the waist-hip ratio decreased across groups, while HOMA-IR was increased. The fasting blood glucose (FBG) level is less in the probiotic group when compared with the control group, while there are no substantial changes in the endotoxin levels [92]. In further research, the effect of the same probiotic mixture was examined for six months while using the same dosage and criteria as the earlier study. Again, a clinically substantial change in the HOMA-IR was noted, and the probiotic group's insulin levels showed a borderline significant improvement [93]. When the flow of lipopolysaccharides (LPS) is decreased, it is anticipated that low-grade inflammation would decrease and insulin signaling will improve. Karczewski et al. assessed the effects of the probiotic *Lactobacillus plantarum*. The probiotic was injected directly into the duodenum of a group of people and followed by a tissue biopsy after 6 hours. According to the authors' observations, zonula occludens-1 and occludin are translocated more often near tight junctions [94]. Similar results for various strains of the *Lactobacillus* genus were obtained in cell cultures [95]. In a nine-month double-blinded, randomized, placebo-controlled research, Hsieh et al.


### **Table 4.**

*Overview of important studies demonstrating the effect of probiotics on human subjects with type 2 diabetes mellitus.*

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

found that T2DM patients who consume capsules containing the probiotic *Lactobacillus reuteri* ADR-1 had lowered cholesterol and HbA1C level in their blood. The reduction in HbA1C was maintained even after three months of follow-up without probiotic treatment [96]. The effects of ingesting *Lactobacillus reuteri* for 12 weeks at various doses (low dose: 108 CFU/day vs. high dose: 1010 CFU/day) were examined by Mobini et al.; however, they were unable to detect a reduction in HbA1C in T2DM patients. In the group consuming high-dosage of probiotic, insulin sensitivity index (ISI) was high [97]. **Table 4** provides an overview of important studies demonstrating the effect of probiotics on human subjects with type 2 diabetes mellitus.

A 12-week probiotic therapy that comprised a multistrain probiotic was administered to 101 adults with T2DM. This intervention revealed that the probiotic intake lowers insulin resistance, fasting blood glucose, and HbA1C levels [101]. In an randomized controlled trial (RCT) by Palacios et al., patients with prediabetes and T2DM were enrolled to examine the outcomes of a probiotic multistrain. The only thing that separated the intervention and placebo groups was an increase in butyrate levels. It is noteworthy that those taking both metformin and a probiotic had decreased levels of insulin resistance, FBG, and HbA1c [102]. In a trial utilizing a single-strain probiotic (108 CFU/day of *Lactobacillus casei* for eight weeks), Khalili et al. discovered a decrease in FBG, insulin concentration, and insulin resistance [103].
