Great question so let’s tackle it step by step.
Hostile Environment Within The Small Intestine:
The small intestine offers varying degrees of environmental difficulties such as a differential pH to the growth and survival of microbial life. After the stomach the food reaches the small intestine in the form of partially digested lump of food called acid chyme. As a result, the pH gets lowered in the small intestine in region with close proximity to the stomach. However, the enzymes in the small intestine responsible for digestion are only active at alkaline condition. As a result to neutralize this acidic condition and to facilitate proper digestion a variety of factors including bile juices, pancreatic juices, secretin, and certain enzymes are released into the lumen of the small intestine which brings the pH in this region to around 8.
Can The probiotic Bacteria Survive In The Small Intestine?
One of the ways through which the probiotics can help the recipient is to colonize the GI tract and aid in the process of digestion. However, in order to be able to succeed in such an endeavour they have to first overcome the harsh conditions that the small intestine has in store for them, i.e., they need to be resistant to both acidic and the alkaline pH as well as factors like the bile salts. Other factors involved include low oxygen content and elevated osmolarity. However, there are strains of both Lactobacillus and Bifidobacterium that have been demonstrated to be able to actively survive in the small intestine. So, there might be mechanisms involved that allows these strains to survive under such extreme physiological conditions.
Resistance Of Probiotics Against Acid And Bile Salts:
The most serious barrier perhaps to the survival of probiotic lives in the small intestine is bile salts. In vitro studies conducted on human subjects have divided the resistance of probiotics to survival and growth. In a study by Pochart et al., it was observed that bile concentrations of 0–1.5% for =3 h. could easily be survived by strains of both the species. Growth experiments in presence of bile salts highlighted yet another fascinating data, the presence of deconjugated bile salts in the growth medium. This goes on to suggest that the probiotic strains have the bile salt hydrolase activities. Other in-vitro studies involved the growth of the strains in presence of 0.3% oxgall, 0.6–3.0 g glycocholic acid/L and taurocholic acid to check their acid resistance capabilities and and some of the strains were found to be well adapted to such acidic environment. These early in-vitro studies went on to suggest that there are many factors that can determine the degree of survival of the probiotics as they pass on through the GI tract-the level of and length of acidity that they have to withstand, the concentration and extent of exposure to the bile salts and degree of bile salt hydrolase activity and yet unspecified properties of the probiotics.
In any case many of the probiotic strains can tolerate these conditions even in-vivo in good enough numbers to reach the colon in viable state where they can affect the micro-environment of the microbes and their metabolism. e.g., in experiments where bifidobacteria were incubated in humans (fed with fermented milk) sampling from the cecum showed a survival to the extent of 23.5%. In an another study by Pochart et al., it was observed that the viability of bifidobacterium did not change significantly at pH.3 (incubated for 3 hours) or pH.1 (incubated for 1 hour) while previous studies have established that the gastric pH remains at ~2.7 for 3 hours which clearly indicates that the specific strains of the probiotics can definitely survive under these conditions.
Genetic Engineering To Confer Bile Resistance To Probitics:
The food borne pathogens are robust in the sense that they are capable of rapid adaptation to a wide array of hostile environments associated with the transit and survival through the GI tract. Sleator et al., had earlier identified a novel bile resistance mechanism designated BilE in the intracellular food borne pathogen Listeria monocytogenes (a Gram-positive bacteria). In a landmark study by watson et al.in 2008, this bile salt resistant gene was cloned and transformed in Bifidobacterium breve and Lactococcus lactis which resulted in greater bile tolerance. Also such strains showed enhanced colonization of the small intestine and higher rate of survival. Some of the researchers are of the opinion that the BilE operon also provides resistance to osmotic stress while others have refuted it. With the fact that small intestine habitation requires high osmotic tolerance, it will be fantastic if it is really the case.
Mechanism And Evolving Technologies To Tolerate Acidic pH
Bacteria growing under acidic conditions show a mechanism known as acid tolerance response (ATR), in which a conglomerate of inducible molecular events are responsible for such a response. Exposure of bifidobacterium to sub-lethal dose of acidic conditions induces ATR thereby triggering its potentail to survive under more severe conditions. This might also be the reason for the possibilty of isolation of acid pH resistant bifidobacteria strains after long exposure to acidic pH. For further refinement about the knowledge of this acid resistance properties, recently Jin et al. has carried out Gene Expression Profile Using RNA-Sequencing of Bifidobacterium longum subsp. longum BBMN 68. Finally, microencapsulation of the probiotic bacteria can provide them the safety against harsh conditions. In a work by Ding et al., a method was developed by the use of palm oil and poly-L-lysine (POPL) as an extra coating to alginate (ALG) microcapsules containing probiotic bacteria. Exciting results followed with the experiment when it was found that such an application of microencapsulation can improve the survival rate of the probiotic bacteria providing resistance to acid and bile. Similar,technologies can be used to combat low oxygen concentration.
With evolving research on tolerance of probiotic bacteria to extreme physiological conditions and the upgradation of genetic engineering technologies can only push the working modalities of the probiotics in the small intestine higher. According to Jay W. MarkS, former Director of the Division of Gastroenterology at Cedars-Sinai Medical Center and an Associate Professor of Medicine, probiotics can definitely work in the small intestine.
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