**5.3 Calcium absorption**

It has been reported that probiotics increase the calcium absorption from intestinal tract. However mechanisms underlying the increasing absorption are not fully elucidated and more than one mechanism may be considered (Gilman et al., 2006). Fermentation products occurred as a result of probiotics' activity may increase the absorption surface by accelerating proliferation in enterocytes (Scholz-Ahrens at al., 2007). Furthermore short chained fatty acids and the other products produced by the bacteria decrease the pH of intestines microenvironment. Therefore, calcium solubility increases and this may be related to increased calcium absorption (Gilman et al., 2006; Scholz-Ahrens at al., 2007). Tang et al.

in epithelial cells of colon by transcriptional mechanisms, it is not effective in jejunum and ileum during its long-term applications. DRA is primary chloride transporter in colon, therefore significance of probiotics in chloride and water absorption has been proved (Binder & Mehta, 1989; Raheja et al., 2009). There is a limited knowledge on the molecular mechanisms underlying the effects of probiotics on sodium absorption. It is well known that probiotics produce short chain fatty acids. The short chain fatty acids increase the expression of NHE-3 which plays a main role in the absorption of sodium from ileum (Kiela

Glucose is absorbed from intestinal brush border membrane by mainly sodium-dependent glucose co-transporters 1 (SGLT-1) and glucose transporter 2 (GLUT-2) (Shimizu et al., 2000). Absorption rate of the intestinal glucose depends on the SGLT-1 affinity and density in the membrane. High affinity SGLT-1 is primary transporter for glucose absorption.

It has been reported that sodium coupled glucose absorption increased in small intestines of pigs treated with *Saccharomyces boulardii* or *Bacillus cereus var*. *toyoi* (Breves et al., 2000). It has been also determined that *Enterococcus faecium* NCIMB 10415 used as a probiotic caused an increase in intestinal transport and barrier function and glucose absorption (Lodeman et al., 2006). Similarly, sodium coupled D-glucose absorption increase has been reported in rats

The mechanism underlying the sodium coupled glucose absorption increasing effect of probiotics in intestinal epithelium cells has not been fully defined. However it has been suggested that specific and non-specific mechanisms may be effective. It may be a nonspecific reason such as an increase in the absorptive surface or in affinity of transporters to substrates due to probiotics. On the other hand Rooj et al. (2010) have reported that supernatant obtained from lactobacilli increased the glucose transport in Caco-2 cells nongenomically and undefined metabolites produced by the probiotic caused this effect. This researchers have suggested that the metabolites produced by the probiotic cause to expression of cytosolic transporters in brush border membranes of enterocytes or to

Although it has been suggested that probiotics affect intestinal glucose transport by nongenomic responses, SGLT-1 expression increases in rats applied *Saccharomyces boulardii* (Buts, 2009). Therefore, it is considered that the probiotics may be effective by changing gene

It has been reported that probiotics increase the calcium absorption from intestinal tract. However mechanisms underlying the increasing absorption are not fully elucidated and more than one mechanism may be considered (Gilman et al., 2006). Fermentation products occurred as a result of probiotics' activity may increase the absorption surface by accelerating proliferation in enterocytes (Scholz-Ahrens at al., 2007). Furthermore short chained fatty acids and the other products produced by the bacteria decrease the pH of intestines microenvironment. Therefore, calcium solubility increases and this may be related to increased calcium absorption (Gilman et al., 2006; Scholz-Ahrens at al., 2007). Tang et al.

et al., 2007).

**-coupled glucose absorption** 

orally applied *Saccharomyces boulardii* (Buts et al., 1999).

activation of transporters which were already in the membrane.

expression via transcriptional or post translational mechanisms.

**5.3 Calcium absorption** 

**5.2 Na<sup>+</sup>**

(2007) reported that fermenting calcium-fortified soymilk with some *Lactobacillus* species can potentially enhance the calcium bioavailability.

Brassart & Yey (1998) have determined that 7 *Lactobacillus* species, which were tested *in vitro*, increased the transepithelial calcium transport in Caco-2 monolayer cells. Gilman & Cashman (2006) have reported that the transepithelial calcium transport did not change in Caco-2 monolayer cells treated by *Lactobacillus salivatorius* (UCC 118) and *Bifidobacterium infantis* (UCC 35624), however UCC 118 increased calcium uptake after 24 hours. Although the differences between the results of these studies have not exactly clarified, it has been suggested that the differences may be due to the different adheration of used bacteria to epithelial cells (Gilman & Cashman, 2006). Intestinal calcium absorption increasing effect of probiotics may be also related to increased expression of calcium channels in intestinal mucosa. Vinderola et al. (2007) observed that supernatant from milk fermented by *Lactobacillus helveticus* R389 enhanced expression of TRPV6 channels in the duodenum. Enhanced expression Ca+2 channels indicate an improved capacity for dietary Ca+2 uptake.

### **5.4 The effects of probiotics on cholesterol absorption**

Cholesterol entered the body via food or re-absorbed from the bile secretion to the blood, is primary factor for heart and vascular diseases. Hypercholesterolemia is one of the most significant risk factor for the cardio-vascular diseases. It has been determined that various probiotic species decrease the serum cholesterol levels in human (Larkin et al., 2009), experimental animals (Park et al., 2007) or farm animals (Özcan et al., 2003; Strompfova et al., 2006). However hypocholesterolemic effect of probiotics depends on the species of the bacteria. This hypocholesterolemic effect has been suggested to be caused by more than one mechanism. For example lactic acid bacteria exert hypocholesterolemic effect by assimilating endogenous or exogenous originated cholesterol in intestinal tract or deconjugating bile acids (Gilliland et al., 1990). In addition, it has been reported that cholesterol and free bile acids bound to the cellular surface of microorganism or co-precipitate with free bile acids by probiotics (Guo & Zhang, 2010).

The recent researches have revealed that probiotics affect gene expression of carrier proteins which are responsible for cholesterol absorption. The protein called Niemann-Pick C1-like 1 (NPC1L1) which is abundantly expressed on the surface of enterocytes, plays a key role on the absorption of cholesterol from intestines. Reduction or inhibition of expression levels of this protein leads to a decrease in plasma cholesterol levels. The probiotic *Lactobacillus acidophilus* (American type culture collection) ATCC 4356 reduced NPCIL-1 gene expression and inhibited the cellular uptake of micellar cholesterol in Caco-2 cells. Soluble effector molecules secreted by ATCC 4356 were shown to be responsible for the decrease in NPC1L-1. Furthermore, ATCC 4356 mediated this effect partly through the liver X receptors (LXR) (Huang & Zheng, 2010).
