The
Pharmaceutical Journal Vol 266 No 7132 p118-121
Probiotic bacteria have been used for many years in food preparation but are now increasingly promoted, along with prebiotics, as “functional foods”. This article looks at the evidence to support their use for a number of diseases
An enormous variety of micro-organisms is required to maintain a healthy environment,
and this applies every bit as much to the internal environment of the gastrointestinal
tract as it does to the oceans, rivers and tropical rain forests. The gut is
populated by about 500 different species of microbe, most of which are non-pathogenic
and help to protect against disease and maintain wellbeing. And because of its
resident bacterial flora, the colon is the most metabolically active organ in
the body, something which has become the subject of increasing research interest
during the past three decades.
Many factors influence the intestinal flora, including age, susceptibility to
infection, immune status, and gastrointestinal pH and transit time. However,
it is probably the amount and type of fermentable material available in the
gut to act as a substrate for microbial growth that has the most effect. Undigested
dietary components contribute to this pool of fermentable material, and this
has led to the idea that diet may exert a significant influence on gut bacteria.
The main fermentable dietary substrates in adults are dietary fibre, resistant
starch, oligosaccharides, some artificial sweeteners and other carbohydrates
that are not absorbed in the small intestine.
The idea that dietary manipulation could be used to improve the microbial environment
in the intestine and improve health has led to the concept of both probiotic
and prebiotic therapy. Of course, such an approach is not new. People have consumed
yogurts and fermented milks for their health for thousands of years. But it
was probably the Russian microbiologist, Elie Metchinikoff, who in the early
years of the 20th century was the first to conduct scientific studies in this
area. Metchinikoff proposed that the health benefits of soured milk products
possibly arose from an antagonistic effect on pathogenic bacteria in the large
intestine. Since that time, the probiotic concept has attracted increasing interest,
particularly during the past 10 years when a number of controlled studies have
demonstrated the possible benefits of this type of therapy.
Although many different definitions of probiotics have been put forward, the
most widely accepted is that a probiotic is “a live microbial food supplement
which beneficially affects the host animal by improving its intestinal microbial
balance”.1,2 For human adult use, this includes
fermented milk products and over-the-counter products, such as powders, tablets
and capsules that contain lyophilised bacteria.
The micro-organisms involved are usually producers of lactic acid, such as lactobacilli
and bifidobacteria, which are widely used in yohurt and dairy products. However,
yeasts have also been used. All these microbes are non-pathogenic and are capable
of surviving passage through the stomach and small bowel, although it is not
certain that all probiotic products contain adequate amounts of live organisms
to have an effect.
Prebiotics differ from probiotics in that they contain no live microbes but
stimulate their growth in the intestine. A prebiotic is defined as a non-digestible
food ingredient which beneficially affects the host by selectively stimulating
the growth, activity or both, of one or a limited number of bacterial species
already resident in the colon.3 Prebiotics are not
digested by intestinal enzymes. Instead they pass through the upper gastrointestinal
tract to the colon, where they are selectively used as fuel by beneficial bacteria.
Although any food residue entering the colon is a potential prebiotic, it is
its influence on certain microbes that is important. Current research tends
to be directed towards foods that enhance the growth and activity of supposed
health-promoting bacteria, such as lactic acid producers. Future research might
look at a possible role for prebiotics that could slow the growth of pathogenic
bacteria.
Lactulose was used more than 40 years ago as a prebiotic infant formula food
supplement to increase numbers of lactobacilli in infant intestine,6
but the specificity of this substrate for enhancing these micro-organisms has
not been effectively proven. In humans, consumption of fructo- oligosaccharides
increases the proportion of bifidobacteria in faeces.7
Similar effects have been observed in rats fed with galacto-oligosaccharides
after their intestines had been colonised with human faecal flora.8
|
Examples of commonly used probiotics and prebiotics4,5
Probiotics
Lactobacilli Lactobacillus acidophilus Gram positive cocci Lactococcus lactis subsp cremoris Bifidobacteria
Yeasts
Prebiotics Fructo-oligosaccharides |
The possible health benefits of probiotics and prebiotics are:
There is a relatively large volume of literature supporting the use of probiotics
for diarrhoea, but it is only recently that the scientific basis for this has
started to become established, with the publication of a number of respectable
clinical studies.
Probiotics have been examined for their effectiveness in the prevention and
treatment of several types of diarrhoea, including antibiotic-associated diarrhoea,
bacterial and viral diarrhoea (including travellers’ diarrhoea), as well as
that caused by lactose intolerance. The effects of probiotics, particularly
with some bacterial strains and in some types of diarrhoea, appear promising,
but the effects of prebiotics on diarrhoea are unknown.
Various mechanisms by which probiotics could be of benefit for diarrhoea have
been proposed and summarised in two reviews.9,10
These include: reduction in gastrointestinal pH through stimulation of lactic
acid-producing bacteria; a direct antagonistic action on gastrointestinal pathogens;
competition with pathogens for binding and receptor sites; improved immune function;
and competition for limited nutrients.
A detailed review11 of all placebo-controlled,
human studies of supplements of Lactobacillus acidophilus, Bifidobacterium
longum, L casei GG and other selected micro-organisms from 1966 to 1995
concluded that “biotherapeutic agents have been used successfully to prevent
antibiotic-associated diarrhoea, to prevent acute infantile diarrhoea, to treat
recurrent Clostridium difficile disease, and to treat various other diarrhoeal
illnesses”. The authors noted that many of the studies included small numbers
of subjects.
Evidence for a beneficial effect of probiotics on diarrhoea appears to be strongest
for that caused by rotavirus infection. Rotavirus infection causes gastroenteritis
characterised by acute diarrhoea and vomiting. Gastroenteritis is a leading
cause of morbidity and mortality among children worldwide. A recent review of
studies that used Lactobacillus, Bifidobacterium and Enterococcus
concluded that Lactobacillus GG (a new Lactobacillus strain isolated
from human intestine) consistently shortened the diarrhoeal phase of rotavirus
infection by one day,12 but that evidence for a
role of Lactobacillus GG and other probiotics in the prevention of diarrhoea
caused by bacterial or other viral infections was less strong.
The prevention of travellers’ diarrhoea by lactobacilli, bifidobacteria, enterococci
and streptococci has been investigated in several studies, but results have
been inconsistent. In a double-blind placebo-controlled trial, 820 Finnish travellers
to two holiday resorts in Turkey were randomised to receive either Lactobacillus
GG or placebo.13 Of the 331 travellers who developed
diarrhoea, 178 (46.5 per cent) were in the placebo group and 153 (41 per cent)
were in the Lactobacillus group, but the difference was not significant.
However, in one of the resorts, the treatment significantly reduced the incidence
of diarrhoea from 39.5 per cent (30 out of 76) in the placebo group to 23.9
per cent (17 out of 71) in the treatment group.
In another study, with 245 travellers to developing countries, the risk of diarrhoea
on any one day in those who took Lactobacillus GG was 3.9 per cent compared
with 7.4 per cent in the control group.14
In another study, the incidence of diarrhoea was reduced from 71 per cent to
43 per cent in travellers to Egypt who were given capsules of Streptococcus
thermophilus, L bulgaricus, L acidophilus and B bifidum.15
However, neither L acidophilus nor Enterococcus faecium had any
beneficial effects on diarrhoea in groups of Austrian tourists.16
In addition, L acidophilus or L fermentum had no effect in soldiers
who were sent to Belize in Central America.17 It
seems that the effect of probiotics on travellers’ diarrhoea depends on the
bacterial strain used and the destination of the traveller.12
Diarrhoea caused by the growth of pathogenic bacteria is the most common side
effect of antibiotic use, and in vitro studies have shown that some benign
bacterial strains can inhibit this growth.
One study has shown that Lactobacillus GG (in yogurt) reduced the incidence
and duration of diarrhoea in healthy men receiving erythromycin for seven days.18
Lactobacillus GG successfully eradicated Clostridium difficile
in five patients with relapsing colitis,19 Enterococcus
SF68 reduced the incidence of diarrhoea caused by antibiotics,20
but studies with L acidophilus21,22 have
provided no conclusive evidence of benefit with this strain in prevention of
diarrhoea caused by antibiotics.
Lactose intolerance is a problem for a large proportion of the world’s population
for whom lactose acts like an osmotic, non-digestible carbohydrate because they
have a low amount of intestinal lactase. During fermentation of yogurt and milk
containing acidophilus, lactobacilli produce lactase that hydrolyses lactose
to glucose and galactose. This predigestion of lactose could reduce the symptoms
associated with lactose intolerance in susceptible individuals. Probiotics have
been shown to improve lactose digestion and intolerance in some studies23,24
but not others.25
The effects of prebiotics on lactose intolerance are unknown, although their
influence on colonic bacterial adaptation may mean that they are beneficial.
One of the claims frequently made for probiotics, specifically for L acidophilus,
is that it can prevent vaginal infections. The conclusions of a review of the
data were that there was evidence - albeit limited - for L acidophilus
in the prevention of candidal vaginitis.11
In a double-blind, controlled, crossover trial of 46 women with a history of
vaginal infections, participants were randomised to receive either L acidophilus
yogurt (150ml/day) containing live organisms or pasteurised yogurt (150ml/day)
for two months each with a two-month wash-out period between interventions.
However, only seven subjects completed the whole study, and the reason for the
high drop-out rate was not explained. The yogurt containing live organisms was
associated with a significant reduction in episodes of bacterial vaginosis.
Both live and pasteurised yogurts were associated with a decrease in candidal
vaginitis, and there was no significant difference between the treatments.26
There is no evidence from controlled trials to show that L acidophilus
used intravaginally can prevent or treat vaginal infections.
The colonic microflora affect systemic and mucosal immunity. Probiotics are claimed to stimulate the immune system and preliminary evidence suggests that these substances could increase the immune response.27,28 However, several studies have used fermented milk enriched with probiotics and it is unclear whether observed effects are due to the probiotics, the fermented milk or both.
Recent research interest has focused on the potential role of probiotics in various conditions known to have an allergic component. There is preliminary evidence that Lactobacillus GG29,30 and Bifidobacterium Bb-1230 could improve symptoms in infants with atopic eczema.
The influence of probiotics on serum cholesterol levels is the subject of
controversy. Studies in the 1970s and 1980s frequently reported significant
reductions in serum cholesterol with daily consumption of fermented milk. These
studies have been criticised on methodological grounds, partly because in most
of the studies showing positive results, large volumes of yogurt (0.5-8.4L)
were consumed.31
Two fairly recent controlled trials have shown that yogurt (200ml daily) containing
live cultures of L acidophilus32 or yogurt
(375ml daily) fermented with L acidophilus with added fructo-oligosaccharides33
(prebiotic) reduced serum cholesterol by 2.9 and 4.4 per cent, respectively.
Another study indicated that inulin (a prebiotic) might also lower cholesterol.34
Observational data suggest that consumption of fermented dairy products is associated with a lower prevalence of colon cancer.35 In addition, there is preliminary evidence from animal studies that both probiotics36 and prebiotics37 could be anti-mutagenic. Two studies in Japanese patients38,39 showed that daily intake of L casei postponed recurrence of bladder tumours, but this finding awaits confirmation. There is currently no conclusive evidence in humans that these products can prevent cancer.
There is some evidence that prebiotics (inulin and oligofructose) can improve calcium absorption.40,41 This effect could enhance bone mineral density, with a consequent reduction in the risk of osteoporosis. However, there are no human studies with prebiotics assessing the risk of osteoporosis.
The colonic microflora are important to health, and modification of the bacterial
species inhabiting the large bowel using probiotics and prebiotics might produce
heath benefits.
The most common probiotics are the lactic acid bacteria and bifidobacteria,
which are used in yogurts and other dairy produce, as well as in dietary supplements.
Many probiotics require refrigeration to maintain viability and, like any other
product, should be used before the expiry date. Commercial products have not
always been found to contain the bacterial strain listed on the label, and in
some cases, the bacteria may not be viable.42
There is a growing number of published papers on the use of both probiotics
and prebiotics. Although they show that both can alter the colonic microflora,
evidence that they can reduce the risk of diseases is more limited. This may
in part be because of differences in methodology, particularly in the number
of different strains that have been used. The evidence for prebiotics in diarrhoea,
particularly Lactobacillus GG in rotavirus infection, is among the best.
There is also some evidence that probiotics can improve lactose intolerance,
boost immunity, prevent vaginal infections and lower serum cholesterol, but
further research is required. Moreover, there is, as yet, no conclusive evidence
that either prebiotics or probiotics can prevent cancer in humans.
Dr Mason is a pharmacist with a postgraduate qualification in nutrition
| Correction In the concluding paragraph, the word "prebiotics" in the sentence "The evidence for prebiotics in diarrhoea, particularly Lactobacillus GG in rotavirus infection, is among the best" should have been "probiotics". |