Delivering Bifidobacterium

Some years ago, I was a bit mystified as to the distinction between prebiotics and probiotics.  These days, one can easily look them up on Wikipedia, and find that prebiotics are meant to encourage the growth of ‘good’ bacteria in the gut, while probiotics are supposed to deliver the bacteria directly. 

Some years ago, I was a bit mystified as to the distinction

between prebiotics and probiotics. 

These days, one can easily look them up on

Wikipedia, and find that prebiotics are meant to

encourage the growth of ‘good’ bacteria in the gut, while probiotics are supposed

to deliver the bacteria directly. 

Prebiotics are generally soluble oligo- or

polysaccharides, known as dietary ‘fibre’, and one of the best sources of these

is chicory root


 
 

Chicory root and

flower

The history of probiotics starts back in the

19th century with the work of Ilya Ilyich

Mechnikov, who received the 1908

Nobel Prize in Physiology or Medicine  for his discovery of phagocytes, along with

Paul

Ehrlich (treatment of syphilis).  Mechnikov’s theory, that certain white

blood cells could engulf and destroy harmful bodies such as bacteria, met with

scepticism from leading specialists including Louis Pasteur, Emil Adolf von

Behring and others. At the time most bacteriologists believed that white

blood cells ingested pathogens and then spread them further through the

body.
 
Mechnikov also developed a theory that aging is caused by toxic

bacteria in the gut and that lactic acid could

prolong life. Based on this theory, he drank sour milk every day. His book

The Prolongation of Life: Optimistic Studies, along with his studies into

the potential life-lengthening properties of lactic acid bacteria, inspired

Japanese scientist Minoru Shirota to

begin investigating the causal relationship between bacteria and good intestinal

health, eventually leading to the development of a bacterial strain

Lactobacillus casei strain shirota which from 1935 is the basis of

Yakult

(ヤクルト the Japanese name

based on ‘yoghurt’: 养乐 or 益力多 ‘benefit happiness/strength a

lot’, depending on where you are in China.)

 
But

— the big question — do the ‘good’ bacteria actually reach the gut?  In order to

reach the intestine, where they are needed, they have to pass the stomach with

its very acidic gastric juice.  Microencapsulation is widely used these days for

delivering drugs (and lots of other things) so why not bacteria?  There has

been, much work on this, reviewed in The Gut Microbiota and

Human Health with an Emphasis on the Use of Microencapsulated Bacterial

Cells [1], which includes a Table of

types of microcapsules available for the targeted delivery of probiotic

bacteria.

Three references there are given to complex capsules made of

the two polymers alginate and chitosan, however there is some more recent

research into developing multilayer systems.  Again, the two main polymers are

the same, namely Alginate, derived from

seaweed, and Chitosan, derived from

crustacean shells.

Alginate

Chitosan

Although these are both polysaccharides, they

have significantly different properties which allow them to work better in

harmony when passing through the stomach.  Alginate is in general a very good

encapsulator, but it does not protect the microbes sufficiently from gastric

juice.  Chitosan, at first sight, seems to labour under two disadvantages.  It

is a known antimicrobial agent and is yet is degraded by microbial action,

especially by the enzyme chitosanase.  (Paradox?  Maybe one is the solid form,

the other in solution).  However, if the inner layer of the capsule is alginate,

chitosan is very slow to diffuse in to the microbes, while chitosan ionically

bound to the alginate is attacked much more slowly by the enzyme.

In

Layer-by-layer

coating of alginate matrices with chitosan–alginate for the improved survival

and targeted delivery of probiotic bacteria after oral administration,

the problem is attacked by building a multilayer fortress around the bacteria.

 The model probiotic, Bifidobacterium breve, were encapsulated

into an alginate matrix before coating in multilayers of alternating alginate

and chitosan.  Bacteria encapsulated in different numbers of multilayers were

treated, and it was found that three layers of chitosan-alginate gave the

greatest survival.  Of just over 1000,000,000 microbes* per millitre, more than

half survived after being soaked in model gastric fluid for the requisite time

(typically 2 hours), whereas unencapsulated bacteria were reduced to less than

1000 per ml.

* strictly speaking, colony-forming units

(CFU).

Bifidobacterium breve is commonly offered as a

probiotic supplement.  The Wikipedia article

deals with the whole Bifidobacterium genus as a whole, but searching for

B. breve yields many results from people marketing probiotic

products, and as sources of information they might be biased, and generically

overlooking the problem of travel through the stomach.  I doubt, though, if we

will see encapsulated bugs in ‘foodie’ products any day soon.  But where someone

has a clinical condition involving imbalance of the intestinal microflora, this

might turn out to be a useful method of delivery.

So does this mean that

there is no point in consuming Yakult?  That would depend on how directly the

bacteria were exposed to stomach fluid.  The advice from one of the authors is

that the bacteria are most vulnerable when the stomach is empty and the pH is

low.  So if you like Yakult, take it with

meals.

[1]

Journal of Biomedicine and Biotechnology; Volume 2011 (2011), Article ID 981214,

12 pages; doi:10.1155/2011/981214
Review Article: The Gut Microbiota and

Human Health with an Emphasis on the Use of Microencapsulated Bacterial Cells by

Satya Prakash, Catherine Tomaro-Duchesneau, Shyamali Saha, and Arielle

Cantor

[2] Journal of Materials Chemistry B, 2013, 1, 52: DOI:

10.1039/c2tb00126h
Layer-by-layer coating of alginate matrices with

chitosan–alginate for the improved survival and targeted delivery of probiotic

bacteria after oral administration
Michael T. Cook, George Tzortzis, Vitaliy

V. Khutoryanskiy and Dimitris Charalampopoulos

Old NID
100455
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