Gut Microbiota, Probiotics, and Human Health

Abstract

The review is devoted to the problems of microbiota and the ways of it correction
employing beneficial life bacteria- probiotics. It covers the issues related to the
functioning of human microbiota and its importance for the health, individual variability
of microbial content, functioning of the probiotics in the human organism and the history
of probiotic studies with particular focus on the microbiological investigations in the
USSR. The article discusses the safety issues related to probiotics and the problems with
probiotic therapy, trying to explain the reasons for the side effects caused by
probiotics. The necessity of personified selection of the probiotic strain or individual
microbial therapy autoprobiotics is also discussed.

Full text

Gut Microbiota, Probiotics, and Human Health
Alexander SUVOROV
1
1
Department of Molecular Microbiology, Institute for Experimental Medicine, Acad. Pavlov Street 12, Saint-Petersburg 197376, Russia
Received November 30, 2012; Accepted April 2, 2013
The review is devoted to the problems of microbiota and the ways of it correction employing benecial life bacteria-
probiotics. It covers the issues related to the functioning of human microbiota and its importance for the health,
individual variability of microbial content, functioning of the probiotics in the human organism and the history of
probiotic studies with particular focus on the microbiological investigations in the USSR. The article discusses the
safety issues related to probiotics and the problems with probiotic therapy, trying to explain the reasons for the side
effects caused by probiotics. The necessity of personied selection of the probiotic strain or individual microbial
therapy autoprobiotics is also discussed.
Key words: microbiota, probiotic, enterotype
INTRODUCTION
The entire concept of the human organism being
located at the top of the evolutionary tree is deeply rooted
in the brain of many people due to traditional, cultural or
religious modes of thinking. This concept was reanalyzed
deeply due to the recent ndings of the damages caused
by the modern civilization to the outer environment and
general public health. Serious ecological catastrophes,
global warming, nuclear waste contamination and
chemical leaks are accompanied by the appearance of
novel important bacterial or viral pathogens, spread of
antibiotic resistance strains and the dramatic increase
in cancer or cardiovascular diseases. All these exo- and
endoecological changes lead to novel modes of thinking
and seeing of the human being as a complex organism
tightly bound to its outer world and its endoecology.
Human civilization witnessed the negative effects of
its own behavior long ago: extensive animal breeding
in the Sahara and destructive and deadly epidemics of
the middle ages in cities with poor sanitary conditions
are the small examples of the importance of equilibrium
between the “outer” nature and “inner” bacterial world.
However, the impact of modern technologies on the
surrounding world and human health surpass all the
previously noticed negative effects. The role of bacteria
as factors inuencing human health has never been fully
understood but was always intuitively acknowledged
by human habits and tradition. Many of the social
restrictions regarding food and diets were and are based
on negative effects of bacterial food contamination or
inability to store certain products properly. In other cases
the benecial health effects of fermented food products
were noticed ages ago and were sometimes considered
sacred. The current review is devoted to the role of the
microbiota in maintaining health and application of
health benecial bacteria in medical practice.
HUMAN MICROBIOTA AS SEEN NOW
The concept of the human microbiota and its role in
human health underwent signicant changes in the eyes of
the scientic community, physicians and common people.
The former attitude of microorganisms as something
alien to humans or even dangerous changed into the
understanding that bacteria (more correct would be the
term “microbiota,” including viruses, bacteria, archaea
and some eukaryotes) are normal and even necessary for
proper functioning of the human organism, populating the
entire body with large a prevalence of microbes in such
loci as the gut, skin, mouth and urogenital system. The
gut is the human organ the most populated by bacteria,
the number of which exceeds by at least by two orders
of magnitude the total number of human body cells [1,
2]. This understanding gradually allowed change the
entire concept of the indigenous microbiota as a vitally
important part of the body and its role in the maintenance
of human health. At present with the advent of new
sequencing technologies and the joint effort of American
and European microbiota analysis programs (Human
Microbiome Project - www.hmpdacc.org and MetaHIT
Corresponding author. Mailing address: Alexander Suvorov, De-
partment of Molecular Microbiology, Institute for Experimental
Medicine, Acad. Pavlov Street 12, Saint-Petersburg 197376, Rus-
sia. E-mail: alexander_suvorov1@hotmail.com
Review
Bioscience of Microbiota, Food and Health Vol. 32 (3), 81–91, 2013

A. Suvorov
82
- www.metahit.eu) the composition and the major
dominant bacterial phyla, representing human microbiota
were identied in contrast to the previous studies based
on classical bacteriology [1]. It is established that
bacterial content of human gut microbiota is composed
mainly from Firmicutes, Bacteriodetes, Actinobacteria,
Proteobacteria, Fusobacteria and Archaea with
predominance of Firmicutes and Bacteriodetes [3, 4].
Indigenous gut microbiota tend to form a complex
multispecies biolm covering entire mucus layer with
only few bacterial species reaching the very gut epithelium
[5]. Composition of human microbiota depends on
the diet preferences of the host but also depend on the
individual peculiarities of the host genetics and his/her
innate immune system. Individual microbial content
seems to be stable during the life span remaining as it
was established quite early in life [6]. Interestingly even
the neonates seem to differ by the predominance of either
Bacteroidetes or Bidobacteriaceae [6]. These individual
features change gradually during life, switching from
bidobacteria being predominant in the breast-feeding
period to the dominance of Bacteriodetes and Firmicutes
in the later stages of life [7]. These discoveries agree with
the nding that the normal microbiota in adults, being
highly individual, has a signicant degree of stability and
tends to recover after temporary dysbiotic conditions.
[8]. The signicant amount of data on the microbiota
sequencing followed by bioinformatic analysis allowed
generation of a concept of enterotypes. According to
the suggestion of Arumugam et al. [9], the human gut
microbiome can be partitioned into three enterotypes:
one with the prevalence of Bacteroides, another with
Prevotella and a third that is almost completely afliated
with phylum Firmicutes with slightly higher levels
of Ruminococcus. This distribution was found to be
independent from the diet preferences, body mass index,
race or gender. It implied a host-controlled microbiota
composition. Almost instantly, this concept of the magic
“three” was challenged by other studies, in which the
existence of two or four enterotypes was found [10, 11].
This fairly articial bioinformatics- based approach of
enterotyping humans, boosted dramatically the research
in the eld because it provided the scientic community
for the rst time with a simple and easily accessible tool
for the analysis of the results of studies of microbiota.
It is already clear that these relatively stable microbiota
compositions (two, three or four) are providing similar
solutions for the organism of the human host at the level
of the metobolome.
The functional role of gut microbiota as an additional
vitally important para-/meta-organ is almost impossible
to overestimate. The gut microbiome participates in
almost all metabolisms of incoming nutrients, is involved
in vitamin synthesis, in cholesterol catabolism, shapes
numerous immune reactions related to the innate and
adaptive immunity, and modulates the relationship of the
human being with pathogenic microorganisms [12, 13].
Indigenous bacteria hydrolyse exogenous and
endogenous substrates. Mucins enable them to obtain
an uninterrupted supply of carbon and energy despite
differences in the human diet. In return bacteria produce
short chain fatty acids (such as butyrate), amines, phenols,
indols, and gases [14]. Even the development of immune
system or the brain depends on the host microbiota [15,
16]. It is also established that many gastrointestinal and
somatic diseases develop as result of microbiota changes
(dysbiosis) inicted by the stress, intoxication, radiation
or antibiotic treatment. Dysbiosis, dened as deregulation
of the normal homeostasis of the intestinal microbiota,
is involved in the pathogenesis of various diseases
including (but not limited to) antibiotic-associated
diarrhea (AAD), Clostridium difcile-associated disease
(CDAD), inammatory bowel disease (IBD), acquired
immune deciency syndrome (AIDS) and obesity [17].
Dysbiotic conditions depending on the degree of the
microbiota disturbances either disappear themselves
or transform into different pathologies, which require
specic microbial (probiotic) treatments.
HISTORY OF PROBIOTICS AND
“RUSSIAN CONNECTION”
Most likely, the rst reason why humans started
selecting certain bacterial stocks for their use was the need
for food preservation. When the access to the food was
sporadic, the ability to preserve the aliments in fermented
form was the only way to prevent hunger. Fermented
milk or meats in the form of cheeses or different kinds of
processed meat (Spanish Jamon Serrano as an example)
were able to preserve the nutritious properties of food for
several months. That was vitally important for farmers
and shepherds, allowing them to make distant journeys
and enhancing dissemination of humankind around
the Earth. Natural selection of the best strains allowed
choosing the best strains and those that were most
advantageous regarding the prevention of food spoilage
and preservation of the nutritional food properties.
During the evolution of human societies, some direct
healing properties of lactic acid bacteria (LAB) strains
were selected based on their health benets. Yogurts,
kers, matsoni, kumis, airan and many other fermented
milk products became known and were sometimes

GUT MICROBIOTA, PROBIOTICS, AND HUMAN HEALTH
83
thought to posses mystical powers because of their health
benets and life-extending properties. At the end of the
19th century, Nobel prize winner Ilia Metchnikoff was the
rst to study LAB scientically. Metchnikoff noticed the
correlation between the longevity of Bulgarian shepherds
and their yogurt diet. In the results of his studies he was
the rst to suggest that humans could live signicantly
longer and healthier if they consume benecial bacteria
[18]. This simple idea happened to be quite sound. In
order to nd the bacteria thriving in yogurts, Metchnikoff
isolated several strains of lactobacilli, which he called
Lactobacillus bulgaricus. He proved that it is possible to
make eatable fermented milk products using pure cultures
of L. bulgaricus. According to Metchnikoff’s hypothesis,
lactobacilli were eliminating pathogenic toxin- producing
bacteria from the colon - what he considered the main
reason for life shortening. His collaborators at the Pasteur
Institute were also the rst to perform experiments on
germ-free animals, starting gnotobiology as a new branch
of biological science. Metchnikoff was not only the rst
to study bacteria in fermented milk; he also promoted
production of the rst bacterial drug, Lactobacillin, which
was manufactured in Saint Petersburg starting 1912. That
was long before Nissle in 1917 suggested his Escherichia.
coli product wrongfully cited as the rst probiotic [http://
www.probiotics-help.com/mutaor.html].
Metchnikoff’s studies were later overshadowed by the
development of antibacterial drugs after the discovery of
antibiotics, and Soviet Union remained the only country
in which scientists continued selecting and analyzing
health benecial strains and certifying them as drugs sold
in pharmacies (Table 1).
Studies of several brilliant Soviet scientists such as
Tsiklinskaia P., Peretz L., Ugolev A., Kiselev P. and
Shenderof B. made a signicant impact in understanding
of the action of health-promoting bacteria in the human
organism and in launch of production of several strains
of health benecial bacteria, belonging to the species of
lactobacilli, enterococci, bidobacteria and E.coli, on an
industrial scale [19–22].
Products containing LAB approved as “drugs” with the
commercial names Lactobacterin, Bidumbacterin and
Colibacterin are still on the market of Russian Federation.
For example, Bidumbacterin – a drug containing
bidobacteria was designed in 1966, and industrial
production of it started in 1972 [23]. “Lactobacterin”
(probiotic drug containing Lactobacillus plantarum
strain 8P-A3) production also was stared in early 70s.
The term probiotic meening food or drugs containing life
health benecial bacteria, appeared in world literature
much later, in the 80s, after the revival of interest in these
benecial bacteria [14]. Around that time, a signicant
Table 1. Probiotic drugs and food products produced and distributed in Russian Federation
Species included Name of the product Type of product Company
Bidobacterium bidum No.1 or
Bidobacterium bidum 791
Bidumbacterin
Bidumbacterin forte
Freeze dried powder 10
8
CFU/ml, 10
7
CFU/g
Biomed Metchnikoff JSC, FSUC
“SIC “Microgen”, Patrner LTD
Bidobacterium bidum No.1 +
Lysozym
Bilis Freeze dried powder, 10
6
CFU/ml Ferment, LTD
Lactobacillus plantarum or
Lactobacillus fermentum
Lactobacterin Freeze dried powder, 10
7
CFU/ml, in 10
ml asks, tablets, vaginal suppositories
Biomed Metchnikoff JSC, FSUC
“SIC “Microgen”IM-Bio
Enterococcus faecium L3 Laminolact Bon-bons with contact dried bacteria 10
6
CFU/g in 200g boxes
Avena, LTD
Lactobacillus acidophilus Acilact Vaginal suppositories 10
7
CFU/ml Lekko, LTD
Bacillus cereus IP 5832 Bactisubtil Freeze dried powder, 10
9
CFU/g in
capsules
Aventis Pharma International,
France
Lactobacillus acidophilus D-76,
D-75
Vitaor Freeze dried powder, 10
7
State Institute of Fine pure
Biochemicals
Escherichia coli М-17 Colibacterin Freeze dried powder, 10
7
CFU/ml, in 10
ml asks
FSUC “SIC “Microgen”
Lactobacillus acidophilus,
Bidobacterium infantis,
Enterococcus faecium
Linex Freeze dried powder, 1.2 × 10
7
CFU/g in
capsules
Sandoz, Lec, Slovenia
Bidobacterium bidum bidum
No.1 and Е. coli М-17
Bicol 10
7
CFU/ml, 10
7
CFU/ml in 10 ml asks Biomed Metchnikoff JSC, FSUC
“SIC “Microgen”
Bidobacterium longum
Enterococcus faecium SF68
Biform 10
7
CFU/ml, 10
7
CFU/ml, in capsules Ferrosan, Denmark

A. Suvorov
84
amount of studies has been already accomplished in
the USSR regarding the selection of probiotic strains,
their antagonistic activities, vitamin production and
specic inuence on the intestinal microbiota. The main
health benets of intestinal bacteria such as antagonistic
activities, vitamin production, enzymatic activities and
immunomodulation were postulated by Leonid Peretz
already in 1955 [19].
PROBIOTICS AND THEIR FUNCTIONS IN
THE HOST
Use of probiotics as health benecial products or
ingredients containing live bacteria is huge, and there is a
constantly growing number of different functional foods
and pharmaceuticals.
Most of the commonly used probiotic strains belong to
the group of LAB and bidobacteria. LAB include several
different genera including Streptococcus, Staphylococcus,
Lactococcus, Pediococcus, Lactobacillus, Enterococcus,
Leuconostoc and some others. LAB had acquired the
ability to recognize several sugars, such as for instance
xylose, cellobiose, ribose, arabinose, glucose, and fructose
before they developed the ability to ferment lactose
to lactate. They rstly colonized fruit and vegetable
ecological niches, and later cheese, wine, and especially
milk, which reected their preference for habitats rich
in lactose [24]. Starting with Metchnikoff, studies of
LAB and their use as probiotics have predominantly
focused on the genus of Lactobacillus. Enterococcus-
based probiotics are well represented in the post-Soviet
and Eastern European market and are less common in
Western Europe and the United States. For example,
the Enterococcus-containing drugs Linex and Biform
are comprise more than 80% of the Russian market for
probiotics (www.gidrm.ru/includes/mktng/marketing ).
Among the other probiotic strains, one should mention
bidobacteria as the dominant microbiota in breast-fed
children which are also prominent as components of both:
probiotic drugs and food products. Other probiotics on
the market belong to different species of bacilli, E.coli,
saccharomyces and some clostridial strains [25, 26].
At present time, a large number of relevant clinical
studies with probiotics have been performed and even
analyzed employing meta-analysis. Some of these
studies aimed at treatment of gastrointestinal diseases
Table 2. Some probiotic strains used in clinical practice
Probiotic strain (preparation) Disease References
VSL#3 (Streptococcus thermophilus Ulcerative colitis [59–61]
Bidobacterium breve
Bidobacterium longum
Bidobacterium infantis
Lactobacillus acidophilus
Lactobacillus plantarum
Lactobacillus casei
Lactobacillus bulgaricus)
Escherichia coli Nissle Ulcerative colitis [62]
Lactobacillus GG Ulcerative colitis [63]
VSL#3 Pouchitis [64]
Lactobacillus GG Crohn’s disease [65, 66]
Saccharomyces boulardii Crohn’s disease [67]
Lactobacillus GG Irritable bowel syndrome [68]
Bidobacterium animalis DN-173 010 Irritable bowel syndrome [69]
Bidobacterium infantis 35624 Irritable bowel syndrome [70]
Escherichia coli (DSM17252) Irritable bowel syndrome [71]
Lactobacillus plantarum MF1298 Irritable bowel syndrome [27]
Lactobacillus plantarum 299v Irritable bowel syndrome [72]
Lactobacillus reuteri ATCC 55730 Irritable bowel syndrome [73, 74]
Bidobacterium bidum CECT 7366 Lactobacillus spp H. pylori infection [75, 76]
Enterococcus faecium L3 H. pylori infection [77, 78]
Clostridium butyricum H. pylori infection [79]

GUT MICROBIOTA, PROBIOTICS, AND HUMAN HEALTH
85
such as irritable bowel syndrome, Crohn’s disease,
pouchitis and ulcerative colitis, are listed in Table 2. The
positive outcomes of probiotic treatment in most of the
studies reect the effectiveness of probiotics in clinical
practice. However, the results of treatments employing
different or even the very same probiotic strain vary
from study to study. For example, in the case of irritable
bowel syndrome (IBS) treatment together with studies
demonstrating positive effects of probiotic therapy, some
studies showed no differences compared with the control
or even the aggravation of pathologies [27–30]. In a
recent study on patients with IBS, intake of L. plantarum
MF 1298 was associated with a signicant aggravation of
symptoms, but neither intake of L. plantarum MF 1298
nor symptoms were associated with the composition of
the fecal microbiota [27]. What was most striking in
this respect was results of a clinical study of patients
with acute pancreatitis, in which 16% of patients in the
probiotics group died, compared with 6% in the control
group [31].
This discrepancy in the results of clinical studies
reects the fact that the probiotic bacteria (sometimes
poorly studied) administered to the individual patients
with their own unique microbiota might interact with the
host tissues or their own microbiota in different ways.
Medical doctors and scientists who made decisions
regarding the clinical studies in many cases neglected the
endoecological aspects of introduction of bacteria into the
gut of patients. These possible side effects of microbial
therapy, which have been proved as effective in most
of the studies, are also postulated by Matsushima and
Takagi in the editorial titled “Is it effective?” to “How to
use it?”: the era has changed in probiotics and functional
food products against Helicobacter pylori infection
[32]. However, accurate prediction of the functioning of
probiotics in the gut is impossible without understanding
the physiology of probiotic strains and the mode of their
interactions with the host.
MECHANISMS OF PROBIOTIC ACTION
In numerous reviews describing the use of probiotics,
several features of the strains included into the
preparations were mentioned. Probiotics should be of
human or animal origins depending on their intended
uses. They should have the ability to survive in sufcient
numbers as well as to pass through the gut (bile and acid
tolerant), be safe for consumption, and be adhesive to the
intestinal mucosa. They should exert an antagonistic effect
against pathogens, and interfere with the translocation of
the pathogenic bacteria and modulate the immune system
[14, 27–30, 33]. However, none of the probiotic strains
meet these criteria in full or the studies showing this are
not convincing. First, the relevance of the probiotic strain
to the host is often questionable due to the fact that most of
the historically selected LAB probiotic strains including
Metchnikoff Lactobacillus delbrueckii subsp. bulgaricus
most likely originated from the cattle microbiota. Three
things regarding probiotic functions are most obvious:
antagonistic potential, the inuence of the probiotics on
the process of digestion and immunomodulation.
Antagonistic activity of most probiotic strains can
be studied outside the host, allowing evaluation of the
range of the affected opportunistic/pathogenic bacteria.
Different mechanisms of antibacterial action are involved,
but synthesis of organic acids and antimicrobial peptides
(bacteriocins) are the most common weapons of bacterial
wars for colonization locus and for nutrients. Expression
of many bacteriocins of lactobacilli, enterococci or
bidobacteria is strictly regulated by the complex
genetic regulatory systems involving three-component
signaling and pheromone activation by the quorum
sensing mechanism [34–36]. The majority of bacteriocin-
producing strains generate peptides inhibiting growth
of a narrow range of bacteria with similar colonization
preferences; however, some probiotics such as L.
plantarum 8P-A3 or E. faecium L3 synthesize multiple
bacteriocins with extremely high inhibitory activities
against gram-positive and gram-negative pathogens [35,
36].
Similar effects were determined in studies with
the other bacteriocins, isolated from LAB [37, 38].
Appearance of probiotics in the gut induces noticeable
metabolic effects on the organism such as lowering of the
cholesterol level, vitamin production, diabetes or obesity
[33, 39–41]. However, it is usually difcult to distinguish
the effects of relatively small amounts of bacteria being
introduced into the total microbiome. These reactions are
better monitored in gnotobiotic animals or animals with
articially induced dysbiosis [42]. On the other hand, a
healthy microbiota is usually resistant to colonization by
external microorganisms [43]. Objective evaluation of
the immunomodulatory functions of probiotics presents
similar problems because the tests are usually performed
either on the organisms with established microbiota or
gnotobionts known to have a defective innate immune
system. Both these models have their weaknesses. It
has been established that probiotics do inuence the
innate and adaptive immune functions involving toll-
like receptors (TLRs) and their downstream systems
including NF-κB, JAKSTAT, MAPK, and SAPK/JNK
pathways. These reactions are followed by interleukin

A. Suvorov
86
and defensin differential expression, which can vary
depending on the type of probiotic used. For example,
the most common reactions to probiotic lactobacilli
or enterococci are downregulation of NF-κB and IL-8
expression and induction of IL-10 [16, 44–47]. However,
these effects are very strain dependant. Different strains
belonging to the same species can modulate the immune
response quite differently by helper T (Th1/Th2) cell
polarization.
Another probiotic feature, which has been under
intensive investigation lately, is their inuence on
epithelium integrity. Probiotics belonging to different
species can inuence protein expression in tight junctions
blocking the process of bacterial translocation [48]. These
effects were more visible in the case when the microbiota
of the experimental animals was in an articially induced
dysbiotic condition [48–50].
PROBIOTICS AND SAFETY
Many scientists and especially physicians active in this
eld are considering only lactobacilli or bidobacteria as
safe probiotics meeting generally regarded as safe (GRAS)
criteria. They are completely ignoring the fact that many
probiotics including the GRAS strains bear putative
pathogenicity factors and mobile genetic elements in
their genomes. On the other hand the strains with a long
history of being successfully used as probiotics belonging
to such species as E.coli, enterococci or Bacillus subtilis
are regarded as potentially hazardous. However, this point
of view has nothing to do with microbial ecology or with
common sense and in reality harms the entire concept
of the clinical usage of probiotics. Bacteria being highly
plastic and adaptive to different environments do not
“respect any human moral values” or do not particularly
target the humans. The only thing they can do and will do
is propagate in the presence of appropriate nutrients and
in certain environments. Many strains of Lactobacillus
salivarius used in several probiotic preparations in reality
express a brinogen-binding protein encoded by the gene
CCUG_2371. The presence of this virulence factor in the
strain can cause platelet aggregation facilitating a septic
infection [51]. The most used and studied probiotic
strain, Lactobacillus rhamnosus GG, carries vancomicin
resistance genes and 5 timidly called “genomic islands”
(in other organisms they are named pathogenicity islands
or the PAI) with several bacteriophages and genes for 3
surface expressed LPXTG-like pilins (spaCBA) and a
pilin-dedicated sortase [52]. These genomic ndings are
considered an explanation of the probiotic features of the
strain [52]. However, the very same genetic features in
other species such as enterococci are considered virulence
factors. This is a good example of a pseudoscientic
approach with double standards that has propagated
under the pressure of large industrial corporations selling
certain types of probiotics. On the other hand this mode
of thinking reects a natural desire to follow the pattern
of commonly accepted stereotypes.
AUTOPROBIOTICS AND FECAL
TRANSPLANTATION
It is of general agreement that at least some health
benets of probiotics occur as result of the interactions
of the probiotic strains or strain composition with the
host microbiota. It also established that the benecial
effects of probiotic are most evident under dysbiotic
conditions and are not seen in the healthy microbiota.
Other solutions for restoring the microbiota back to
normal are fecal transplantation or autoprobiotic therapy.
Fecal transplantation is a medical procedure based on the
replacement of the host microbiota with the microbiota
of a donor. This procedure had been evaluated in several
clinical studies on patients with inammatory bowel
disease (IBD) or for the treatment of Clostridium difcile
infection [53, 54]. Besides being fairly unhealthy way
to introduce bacterial biomass (through the nose or the
rectum), this approach has Achilles’ heels such as the
donor microbiota, which may carry opportunistic bacteria
able to cause problems in the treated patient. In our
previous study of healthy individuals, about 50% of the
indigenous enterococci carried several putative virulence
factors in their genome [55]. Also, the enterococci are
clearly not the most dangerous bacteria in the gut.
Another approach is based on the indigenous bacteria
used for restoring the normal microbiota in the case
of a dysbiotic condition [20]. This approach, named
as autoprobiotic technology, can be based on LAB or
bidobacteria previously stored in cryobanks, isolation of
individual strains from the microbiota and returning the
bacteria back into the gut after propagating them outside
the organism, allowing analysis of each individual strain
and return of it to the host. Usually it takes a week to
prepare autoprobiotic yogurt for the patient. In our
clinical studies of patients with IBS, ulcerative colitis
and pneumonia autoprobiotics introduced to patients by
employing a randomized placebo-controlled approach
provided signicant positive effects as judged from the
majority of clinical parameters and life quality [56].

GUT MICROBIOTA, PROBIOTICS, AND HUMAN HEALTH
87
CONCLUSIONS
Contemporary science is collecting more and more
data regarding the human microbiota, which functions as
an important “organ” tightly bound to the other organs
of the body. Previous dogmas of clinical microbiology,
which were trying to divide the microbial world into
hazardous and benecial microorganisms, are questioned
by the new genomic and metabolomic data. The
contemporary crisis of pharmacology being unable to
produce and bring new antibiotics into the market [57]
is giving human race a chance to see the problem of
human health from the level of microecology, moving
away from the simple eradication strategy. The emotional
appeal of Blaser, “Stop the killing of benecial bacteria,”
needs to attract more attention from the scientic and
medical community [58]. It is obvious that the tight
systemic links between the microbiota and the cells of
the human body are highly individualized and need to
be restored when the microbiota changes due to various
reasons, with antibiotic treatments being number one.
Dysbiotic conditions lay underneath many infectious and
somatic diseases of our contemporaries. It is obvious that
microbial therapy should be much better implemented
in the arsenal of medical doctors; however, a signicant
amount of studies needs to be done before this kind of
therapy will become really common.
Despite the great number of different probiotics
on the world market and permanently growing sales
of probiotics, there is no agreement in the scientic
community regarding their mode of functioning and
interpretation of the results of the clinical studies. The
main reason for this is simply based on the lack of the
relevant studies and extremely complex microbiota of
each individual. There is no common agreement on the
expected features or the composition of probiotic strains.
Only several things about probiotics are obvious: we want
them to pass alive to the target locus of the organism,
interact with the host microbiota and the host immune
system and they should not cause an infection.
On the other hand there are a lot of things they are
supposed to do: they supposedly must deplete a number
of opportunistic bacteria, somehow modulate the immune
system, most likely consume internal nutrients and
produce their own metabolites, strengthen the epithelial
barriers, colonize sites in the organism or disappear from
the host. There is no agreement: regarding the issues of
the preferred period of colonization, ability of probiotics
to adhere to the host epithelium, afliation of probiotics
to the indigenous human microbiota, and the features
regarding the safety of the probiotic strains. Most of these
issues of scientic disagreement are being minor but at
rst glance require clarication. For example, the ability
to colonize the epithelium in bacteria is often correlated
with the presence of the adhesins, which are considered
virulence factors on bacterial surfaces. Thus the presence
of the adhesions or mbriae on the surface of the probiotic
bacteria can be judged differently.
There is no agreement regarding the preferred time of
colonization and very limited data on monitoring the fate
of probiotic strains inside the organism. The preferred
dosage of probiotic bacteria is not clear too. Most likely,
the optimal amount of consumed probiotic bacteria is
strain specic and depends on the survival of the probiotic
bacteria in the host.
It is unclear what is better: one probiotic strain or a
multistrain composition. The interrelationship between
the strains of such probiotic compositions is the mostly
poorly studied. In any case, the more alien strains are
introduced into the gut, the more chances there are that
one of the members of the consortiums will cause an
unpredicted reaction.
In this respect the idea using indigenous strains as
probiotics looks quite attractive. Autoprobiotic strains
have better chances relative to probiotics to colonize the
host and thus normalize the host microbiota. However,
autoprobiotics as medical therapies require further study.
In spite of the obstacles and the problems with
microbial therapy stated in the present overview, the
body of evidence concerning the use of probiotics in
medicine is substantial, and better solutions for returning
the individual microbiota back to normal are not on the
horizon.
ACKNOWLEDGEMENTS
I am thankful to my colleagues for constructive advise
regarding this review.
Major help was provided by Thomas Haertle from INRA,
France, who kindly edited the text and gave many important
critical remarks. I am also thankful to my Russian colleagues
Ekaterina Kisseleva from the Institute of Experimental
Medicine, Galina Alechina from Avena Ltd and Vetchaslav
Melnikov from ITSC for the constructive criticism and
some suggestions. Some experimental data sited in the
review were collected in the Department of Molecular
microbiology, Institute Experimental Medicine Russia. This
work was supported by RFBR grant 10-04-00750a.
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