**10. The applications of probiotics in diabetes**

Probiotics are dietary supplements containing bacteria which, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO 2002). Combinations of different bacterial strains can be used (Bezkorovainy 2001) but a mixture of *Lactobacilli* and *Bifidobacteria* is a common choice (Karimi & Pena 2003). Probiotics have been shown to be beneficial in wide range of conditions including infections, allergies, metabolic disorders such as diabetes mellitus, ulcerative colitis and Crohn's disease (Altenhoefer et al. 2004; Rozanova et al. 2002; Ziegler et al. 2003).

There are reports in the literature that probiotic treatment can be useful in diabetes (Al-Salami et al. 2008b) but there is little explanation of the mechanisms involved. The initial site of diabetogenic cells has been hypothesized to be in the gut whereas pancreatic lymph nodes serve as the site of amplification of the autoimmune response (Jacobs et al. 1989). This autoimmune response may disturb the composition of the normal gut flora. Treatment with *Bifidobacteria* and *Lactobacilli* has been shown to normalize the composition of the gut flora in children with T1D (Rozanova et al. 2002). In addition, the administration of *Lactobacilli* to alloxan-induced diabetic mice prolonged their survival (Matsuzaki et al. 1997a) and administration to non-obese diabetic (NOD, a rodent model of T1D) mice inhibited diabetes development possibly by the regulation of the host immune response and reduction of nitric oxide production (Matsuzaki et al. 1997b). Furthermore, the administration of a mixture of *Bifidobacteria*, *Lactobacilli* and *Streptococci* to NOD mice was protective against T1D development postulated to be through induction of interleukins IL4 and IL10 (Calcinaro et al. 2005).

Slowing of peristalsis (gastroparesis) has been reported in T1D patients. This can result in a bigger population of bacteria in the gut and a subsequent rise in the concentration of secondary bile acids (Meinders et al. 1981a) such as lithocholic acid which is toxic at high concentrations and can induce gut inflammation and blood dyscrasias (Malavolti et al. 1989; Miyai et al. 1982). In addition, the disturbed bile acid composition in T1D (Meinders et al. 1981a) is strongly linked with autoimmune and liver diseases. The administration of *Lactobacilli* and *Bifidobacteria* may restore the bile acid composition (Kurdi et al. 2000; Kurdi et al. 2006). It is important to select the right probiotic species based on efficacy, stability in


Table 1*.* pH and bile tolerability of Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis.

Probiotics are dietary supplements containing bacteria which, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO 2002). Combinations of different bacterial strains can be used (Bezkorovainy 2001) but a mixture of *Lactobacilli* and *Bifidobacteria* is a common choice (Karimi & Pena 2003). Probiotics have been shown to be beneficial in wide range of conditions including infections, allergies, metabolic disorders such as diabetes mellitus, ulcerative colitis and Crohn's disease (Altenhoefer et al. 2004;

There are reports in the literature that probiotic treatment can be useful in diabetes (Al-Salami et al. 2008b) but there is little explanation of the mechanisms involved. The initial site of diabetogenic cells has been hypothesized to be in the gut whereas pancreatic lymph nodes serve as the site of amplification of the autoimmune response (Jacobs et al. 1989). This autoimmune response may disturb the composition of the normal gut flora. Treatment with *Bifidobacteria* and *Lactobacilli* has been shown to normalize the composition of the gut flora in children with T1D (Rozanova et al. 2002). In addition, the administration of *Lactobacilli* to alloxan-induced diabetic mice prolonged their survival (Matsuzaki et al. 1997a) and administration to non-obese diabetic (NOD, a rodent model of T1D) mice inhibited diabetes development possibly by the regulation of the host immune response and reduction of nitric oxide production (Matsuzaki et al. 1997b). Furthermore, the administration of a mixture of *Bifidobacteria*, *Lactobacilli* and *Streptococci* to NOD mice was protective against T1D development postulated to be through induction

Slowing of peristalsis (gastroparesis) has been reported in T1D patients. This can result in a bigger population of bacteria in the gut and a subsequent rise in the concentration of secondary bile acids (Meinders et al. 1981a) such as lithocholic acid which is toxic at high concentrations and can induce gut inflammation and blood dyscrasias (Malavolti et al. 1989; Miyai et al. 1982). In addition, the disturbed bile acid composition in T1D (Meinders et al. 1981a) is strongly linked with autoimmune and liver diseases. The administration of *Lactobacilli* and *Bifidobacteria* may restore the bile acid composition (Kurdi et al. 2000; Kurdi et al. 2006). It is important to select the right probiotic species based on efficacy, stability in

**strain pH tolerability Bile tolerability** 

Table 1*.* pH and bile tolerability of Lactobacillus rhamnosus, Lactobacillus acidophilus and

Good survival rate in 3% bile salts for up to 24 hours (Succi et al. 2005).

Good survival rate in 4% bile for up to 12 hours (Favaro-Trindade & Grosso 2002).

Good survival rate in 4% bile for up to 12 hours (Favaro-Trindade & Grosso 2002).

At pH < 2 (after 2 hours) reduction by 2 – 3 log CFU/ml At pH < 1 (after 2 hours), reduction by 6 – 8 log CFU/ml (Succi et al. 2005).

At pH < 1 (after 1 hour), reduction by 1 log CFU/ml (Favaro-Trindade & Grosso 2002).

At pH < 1 (after 1 hour), reduction by 1 log CFU/ml (Favaro-Trindade & Grosso 2002).

**10. The applications of probiotics in diabetes** 

of interleukins IL4 and IL10 (Calcinaro et al. 2005).

**Probiotic** 

*Lactobacillus rhamnosus*

*Lactobacillus acidophilus*

*Bifidobacteri um lactis*

Bifidobacterium lactis.

Rozanova et al. 2002; Ziegler et al. 2003).

the gut (bile and pH tolerability) and long term safety. Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis show good bile and pH tolerability under normal conditions of pH (1.5-8) and bile acid concentration (0.8 – 3 %) (Table 1), in addition to long term safety (Franz & Bode 1973; Hedenborg & Norman 1984; Hedenborg & Norman 1985).
