**3. The effect of probiotics on the motility of the gastrointestinal tract**

Either gastrointestinal motility or the kinetic of its content is one of the most important variations providing gastrointestinal tract's comfort. The changes in motility can make symptoms varying from constipation to diarrhea come into being (Ohashi & Ushida, 2009). The interest to probiotics, due to their motility regulatory effects, is rising in functional gastrointestinal disorders.

The influence of microorganisms on intestinal motility was reported for the first time by Abraham and Bishop. These researchers observed that both small and large intestinal transit time and gastric emptying decreased in germ-free animals (Abraham & Bishop, 1967). Husebye et al. (1994) detected that phase-3 intervals in migrating motor complex (MMC) in germ-free animals were extended. In addition, they noticed that the motility became normal when specific pathogen free bacteria were inoculated in these animals' intestines. They also noticed that the motility of intestines became normal when probiotics were inoculated instead of doing so with commensal bacteria.

Actually gastrointestinal motility and microorganisms in the tracts are mutually influencing each other. The presence or the absence of the motility affects microorganisms' colonization and also the motility is being altered in case the microorganisms are lacking. Both migrating motor complex in stomach and the one way peristaltic movements in small intestine influence the colonization in the area (Quigley, 2011). Thus the decrease of intestinal motility causes small intestinal bacterial overgrowth (SIBO).

In addition to commensal bacteria in gastrointestinal tract, those used as probiotic were also detected to be influencing the motility (Williams et al., 2010). Diverse researches related to the subject in both human and animal models were conducted. Massi et al. (2006), observed *in vitro* the influence of probiotics on motility in ileum and proximal colon segments isolated from guinea pigs. They realized that *Lactobacillus* and cytoplasmic extract obtained from *Bifidobacterium* caused a contraction in ileum and a relaxation in proximal colon. They claimed that the extract mentioned above does not exert its effect via muscarinic receptors

The Impact of Probiotics on the Gastrointestinal Physiology 57

secreted by bacteria or final products formed at the end of fermentation 2) Influence of microorganisms on intestinal neuroendocrine factors 3) Influence of mediators secreted due

The stimulation of colonic motility via the rise of fecal bacterial mass, the stimulated cholecystokinin and deconjugated or dehydroxylated bile salts is considered to be a part of other mechanisms. Some probiotics such as *Bifidiobacteium lactis* HN019 stimulate the production of lactic acid bacteria in the environment. As a consequence of lactic acid bacteria production, WGTT time decreases while peristaltic accelerates owing to the

A high number of gas occurring due to the digestion of indigested carbohydrates by colonic microbiota influences intestinal motility. Yet different influences may occur in motility related to the gas type formed. For example, when methane producing bacteria in intestinal flora multiplies, compared to the effects of those releasing hydrogen, intestinal transit time increases, motor activity is directly inhibited, and on the contrary non propulsive and

Short chain fatty acid (SCFA) appearing as an outcome of carbohydrate or lipid fermentation by probiotics is one of the most important final products influencing gastrointestinal motility. Cherbut et al. (1997) observing the influence of SCFA on motility detected that SCFA showed contractile activity via enteric cholinergic reflex in low concentrations (0.1 to 10 mmol/L). Nevertheless this was also detected to be a temporary effect. SCFA in high concentrations (100 mmol/L) was observed to inhibit colonic contraction (Sakata, 1987). McManus et al. (2002) reported that SCFA inhibits peristaltic activity while it stimulates the tonic activity in the large intestine of dogs. It exerts this effect by influencing Ca+2 influx to gastrointestinal smooth muscle cells. Besides colonic motility SCFA was also determined to influence upper part of digestive tract, to cause relaxation in both lower esophageal sphincter and proximal stomach and also it decreases gastric emptying time. It was explained that it showed this effect via hormonal way with the use of

In addition, probiotics affect the motility in an indirect way by influencing some inflammatory mediators' expression occurring during the disease that alters gastrointestinal tract functions. For example, *Lactobacillus paracasei* weaken the hyper contractility rising in the post infective period of diseases by increasing the expression of COX-2 being one of the inflammatory mediators (Verdu et al., 2004). Mediators such as TGF-β and prostaglandin E(2) released during gastrointestinal diseases damage both enteric nervous system and interstitial cells of cajal. Disorders in the motility occur since the neuronal structures mentioned above regulate intestinal tract motility. Probiotics given in post infective period normalize the motility as they accelerate the healing of damaged cells in enteric nervous

There is only limited research on the effects of probiotics on pancreatic digestive enzymes such as amylase, lipase, trypsin, chymotrypsin, although there are few publication related to effects of probiotics on mucosal digestive enzymes. The relation between microorganisms of intestinal tract and pancreatic enzymes has been investigated in some studies using germ-

**4. Effects of probiotics on pancreatic digestive enzymes** 

to gastrointestinal tract's immune reaction (Barbara et al., 2005).

reduction of the intestinal content pH (Salminen et al., 1997).

segmental contractions increase (Pimentel et al., 2006).

polypeptide YY (Labayen et al., 2001).

system (Indrio et al., 2008).

since its effect was not inhibited by atropine. Yet, its mechanism is not fully elucidated so far (Waller et al., 2011).

The motility-probiotic relationship in humans was both in healthy individuals and in case of different diseases evaluated despite of technical difficulties. Indrio et al. (2008) who observed the connection between gastric emptying and the probiotics determined that gastric emptying time in infants being given *Lactobacillus reuteri* was significantly rapid compared to those in placebo group. Cherbut et al. (1997) noticed that the motility of terminal colon rises while sleeping in humans supplemented with *Lactobacillus casei*. Marteau et al. (2002) reported *Bifidobacterium lactus* strain DN 173010 to reduce colonic transit time in healthy female individuals. Waller et al. (2011) explained that whole gut transit time (WGTT) decreased in a dose-dependent manner in male and females obtaining different doses of *Bifidobacterium lactis* HN019 during 14 days.

Indrio et al. (2009) observing electrical activity that forms motility reported that the percentage of propagation (the electric activity turning into peristaltic movement) was higher in infants to which *Lactobacillus reuteri* was given compared to those in placebo group.

Lots of diseases such as irritable bowel syndrome (IBS) causing gastrointestinal dysfunction, also influence digestive tract motility or its motor activity. Probiotics are used in treatment of motoric function disorders seen in such diseases' post infective periods. For example post infective period hyper contractility was observed to be present in digestive tract of mice infected with *Trchinella spiralis*. It has been observed that the hyper contractility in mice given *Lactobacillus paracasei* NCC2461 specifically weakened (Verdu et al., 2004). In the same way delayed gastric emptying was observed in mice infected via *Helicobacter pylori*. Gastric functions were detected to be normalized in the same mice following probiotic treatment with *Lactobacillus rhamnosus* R0011 and *Lactobacillus helvaticus* R0052 (Verdu et al., 2008). Agrawal et al. (2009) reported that both colonic and orocecal transit were accelerated when fermented milk product containing *Bifidobactreium lactis* DN-173010 were given to patients suffering from irritable bowel syndrome presented with abdominal distension and constipation and also that this was making the case symptoms' influences to be diminished. Intestinal transit time was detected to be lengthened in diseases representing with digestive tract functional disorders such as IBS. Even the mechanism that lies beneath is not fully elucidated; it was estimated to be related to the imbalance in intestinal micro flora due to the illness itself.

The effects of probiotics on intestinal tract are being influenced by diverse factors. The motility in intestinal tract was acclaimed to be possibly specific to the type of the probiotic used (Husebye et al., 2001). Either the physiologic situation of the human or the animal is another factor affecting the motility. For example it was detected that in elderly people, *Bifidobacterium* DN 173010 reduces oro-fecal transit time while the same bacteria accelerates only colonic transit time in healthy volunteers. In addition, its effects in males were established to differ from that in females (Meance et al., 2001).

#### **3.1 The mechanism of action**

The mechanism lying beneath the effects of probiotics on motility are not fully elucidated. Yet the probable influence mechanisms can be divided into three headlines; 1) Products

since its effect was not inhibited by atropine. Yet, its mechanism is not fully elucidated so far

The motility-probiotic relationship in humans was both in healthy individuals and in case of different diseases evaluated despite of technical difficulties. Indrio et al. (2008) who observed the connection between gastric emptying and the probiotics determined that gastric emptying time in infants being given *Lactobacillus reuteri* was significantly rapid compared to those in placebo group. Cherbut et al. (1997) noticed that the motility of terminal colon rises while sleeping in humans supplemented with *Lactobacillus casei*. Marteau et al. (2002) reported *Bifidobacterium lactus* strain DN 173010 to reduce colonic transit time in healthy female individuals. Waller et al. (2011) explained that whole gut transit time (WGTT) decreased in a dose-dependent manner in male and females obtaining

Indrio et al. (2009) observing electrical activity that forms motility reported that the percentage of propagation (the electric activity turning into peristaltic movement) was higher in infants to which *Lactobacillus reuteri* was given compared to those in placebo

Lots of diseases such as irritable bowel syndrome (IBS) causing gastrointestinal dysfunction, also influence digestive tract motility or its motor activity. Probiotics are used in treatment of motoric function disorders seen in such diseases' post infective periods. For example post infective period hyper contractility was observed to be present in digestive tract of mice infected with *Trchinella spiralis*. It has been observed that the hyper contractility in mice given *Lactobacillus paracasei* NCC2461 specifically weakened (Verdu et al., 2004). In the same way delayed gastric emptying was observed in mice infected via *Helicobacter pylori*. Gastric functions were detected to be normalized in the same mice following probiotic treatment with *Lactobacillus rhamnosus* R0011 and *Lactobacillus helvaticus* R0052 (Verdu et al., 2008). Agrawal et al. (2009) reported that both colonic and orocecal transit were accelerated when fermented milk product containing *Bifidobactreium lactis* DN-173010 were given to patients suffering from irritable bowel syndrome presented with abdominal distension and constipation and also that this was making the case symptoms' influences to be diminished. Intestinal transit time was detected to be lengthened in diseases representing with digestive tract functional disorders such as IBS. Even the mechanism that lies beneath is not fully elucidated; it was estimated to be related to the imbalance in intestinal micro flora due to the

The effects of probiotics on intestinal tract are being influenced by diverse factors. The motility in intestinal tract was acclaimed to be possibly specific to the type of the probiotic used (Husebye et al., 2001). Either the physiologic situation of the human or the animal is another factor affecting the motility. For example it was detected that in elderly people, *Bifidobacterium* DN 173010 reduces oro-fecal transit time while the same bacteria accelerates only colonic transit time in healthy volunteers. In addition, its effects in males were

The mechanism lying beneath the effects of probiotics on motility are not fully elucidated. Yet the probable influence mechanisms can be divided into three headlines; 1) Products

different doses of *Bifidobacterium lactis* HN019 during 14 days.

established to differ from that in females (Meance et al., 2001).

(Waller et al., 2011).

group.

illness itself.

**3.1 The mechanism of action** 

secreted by bacteria or final products formed at the end of fermentation 2) Influence of microorganisms on intestinal neuroendocrine factors 3) Influence of mediators secreted due to gastrointestinal tract's immune reaction (Barbara et al., 2005).

The stimulation of colonic motility via the rise of fecal bacterial mass, the stimulated cholecystokinin and deconjugated or dehydroxylated bile salts is considered to be a part of other mechanisms. Some probiotics such as *Bifidiobacteium lactis* HN019 stimulate the production of lactic acid bacteria in the environment. As a consequence of lactic acid bacteria production, WGTT time decreases while peristaltic accelerates owing to the reduction of the intestinal content pH (Salminen et al., 1997).

A high number of gas occurring due to the digestion of indigested carbohydrates by colonic microbiota influences intestinal motility. Yet different influences may occur in motility related to the gas type formed. For example, when methane producing bacteria in intestinal flora multiplies, compared to the effects of those releasing hydrogen, intestinal transit time increases, motor activity is directly inhibited, and on the contrary non propulsive and segmental contractions increase (Pimentel et al., 2006).

Short chain fatty acid (SCFA) appearing as an outcome of carbohydrate or lipid fermentation by probiotics is one of the most important final products influencing gastrointestinal motility. Cherbut et al. (1997) observing the influence of SCFA on motility detected that SCFA showed contractile activity via enteric cholinergic reflex in low concentrations (0.1 to 10 mmol/L). Nevertheless this was also detected to be a temporary effect. SCFA in high concentrations (100 mmol/L) was observed to inhibit colonic contraction (Sakata, 1987). McManus et al. (2002) reported that SCFA inhibits peristaltic activity while it stimulates the tonic activity in the large intestine of dogs. It exerts this effect by influencing Ca+2 influx to gastrointestinal smooth muscle cells. Besides colonic motility SCFA was also determined to influence upper part of digestive tract, to cause relaxation in both lower esophageal sphincter and proximal stomach and also it decreases gastric emptying time. It was explained that it showed this effect via hormonal way with the use of polypeptide YY (Labayen et al., 2001).

In addition, probiotics affect the motility in an indirect way by influencing some inflammatory mediators' expression occurring during the disease that alters gastrointestinal tract functions. For example, *Lactobacillus paracasei* weaken the hyper contractility rising in the post infective period of diseases by increasing the expression of COX-2 being one of the inflammatory mediators (Verdu et al., 2004). Mediators such as TGF-β and prostaglandin E(2) released during gastrointestinal diseases damage both enteric nervous system and interstitial cells of cajal. Disorders in the motility occur since the neuronal structures mentioned above regulate intestinal tract motility. Probiotics given in post infective period normalize the motility as they accelerate the healing of damaged cells in enteric nervous system (Indrio et al., 2008).
