BIFIDOBACTERIUM LACTIS BI-07 ®

TM 55-3 US 7.19
Technical Memorandum

Benefits summary administered in adequate amounts, probiotic strain to be successful, it has

Extensive in vitro and in vivo studies confer a health benefit on the host to fulfill certain requirements. These
support the health-enhancing, (Hill et al, 2014). will improve its functionality in the
probiotic properties of B. lactis Bi-07. intestine after consumption and
These attributes can be summarized Most probiotics are either lactobacilli enhance its survival in the product.
as follows: or bifidobacteria, although species of
other microbial genera are also • The strain must be safe and thus
• Long history of safe use reported to have probiotic properties. free from potential risk-genes. This
• Well-suited to intestinal survival The beneficial effects of probiotics requires identification by appropriate
- High tolerance to gastrointestinal either involve reducing risk factors for molecular techniques
conditions (acid and bile) a certain disease or improving some • The strain has to be able to resist
- Strong adhesion to intestinal cell of the body’s natural functions, acid and bile
lines thereby helping to maintain the • The strain must have scientifically
• Improves gastrointestinal health health of the consumer. So far, these proven health benefits
and well-being effects have been documented • The strain should have good
• Beneficial modulation of immune primarily in two areas, which are also technological properties, such as
functions the main areas of probiotic research the ability to survive in the final
for DuPont: consumer product in sufficient
Introduction counts until end of shelf-life,
A growing awareness of the • gastrointestinal well-being whether food or dietary
relationship between diet and health • beneficial modulation of the immune supplements.
has led to an increasing demand for system
products that are able to enhance The only certain way to establish the
health beyond basic nutrition. Studies The suggested health benefits of true quality and value of a probiotic
have shown that ingestion of probiotics are many. It should, strain is by systematic in vitro and in
probiotics, or health-promoting however, be noted that each probiotic vivo studies and, in particular, human
bacteria, is beneficial for maintaining strain has its own specific health clinical trials.
the microbial balance in the body. benefits, and no probiotic strain elicits
all the health benefits proposed for Characteristics of the species
This balance is known to particularly
probiotics in general. Furthermore, Bifidobacterium spp. are anaerobic,
enhance intestinal health and the
when one probiotic strain has a Gram-positive, non-spore forming,
immune system, as well as other
certain health benefit, it cannot be pleomorphic lactic acid bacteria
physiological functions, making it a
assumed that another strain, not even commonly found in the guts of
critical factor for general human
of the same species, has similar healthy humans and infants
well-being (de Moreno de LeBlanc
properties. (Arumugam et al, 2011; Mitsuoka 1996;
and LeBlanc, 2014; Kechagia et al,
Scardovi et al, 1986; Turroni et al,
2013; Vandenplas et al, 2015). The origin of a bacterial strain, e.g., 2009; Ventura et al, 2007).
Probiotics are defined as: live the human gastrointestinal tract, is no Bifidobacteria were discovered in
microorganisms that, when guarantee or precondition for its 1899 in the feces of breast-fed infants.
performance as a probiotic. For a

1
This was of particular interest to
scientists as these bacteria are
typically the most abundant species
present in the intestine of breastfed
infants and regarded as a primary
reason for the infants’ greater
resistance to disease. Today
bifidobacteria are broadly recognized
for their key role in the human
intestinal microbiota throughout life.
A high proportion of bifidobacteria in
the intestinal tract is considered
beneficial to health.

Selection and taxonomy

Bifidobacterium lactis was originally
described by Meile et al (Meile et al,
Figure 1. Scanning electron micrograph of Bifidobacterium lactis Bi-07 (©DuPont)
1997) and was recently re-classified as
B. animalis subsp. lactis (Masco et al,
2004). In the interests of simplicity, INDELs can be applied to differentiate safety (Aguirre et al, 1994; Salminen
DuPont refers to strains of this species between B. animalis subsp. lactis et al, 1998; Borriello et al, 2003; Boyle
as B. lactis. B. lactis Bi-07 has been strains by a method described by et al, 2006). Furthermore, B. lactis has
genetically characterized and Briczinski et al. The strain-specific been present in human food for
properly classified as B. lactis by typing technique can be used in decades.
independent labs using modern clinical, regulatory, and commercial
This species B. lactis is considered
genotypic methods, including 16S settings to identify the selected strain
safe for human consumption and
rRNA gene sequencing and PCR using (Briczinski et al, 2009). Furthermore, a
marketed as a food supplement
species-specific primers (Ventura and thorough assessment for safety
worldwide. The strain B. lactis Bi-07 is
Zink, 2002). B. lactis Bi-07 is of human showed no evidence of genetic risk
manufactured in accordance with U.S.
origin and has been shown to grow elements (Morovic et al, 2017)
Food & Drug Administration’s (FDA)
well in milk. B. lactis Bi-07 has been regulations. B. lactis strain Bi-07, is
deposited in the American Type Consistent strain identity
recognized as GRAS with no objection
Culture Collection’s safe deposit as For a strain with documented probiotic
from U.S. FDA (GRAS Notification
SD5220. activity, it is very important that it is
#445, U.S. Food & Drug
not subjected to any genetic or
Genomics Administration, 2013). It is enlisted in
physiological change during
The complete genome sequence of the Inventory of Microorganisms with
processing. To maintain the quality,
B. lactis Bi-07 has been published, Documented History of Use in Human
purity, and consistency of each
allowing for more stringent strain Food (Bourdichon 2012) and the
production batch of the strain, DuPont
identity confirmation among other Qualified Presumption of Safety list
makes rigorous bacterial frozen seed
genetically similar B. lactis strains by EFSA (Ricci et al, 2017). No harmful
inventories to reduce the risk of
(Stahl and Barrangou, 2012). The metabolic or toxigenic activities are
genetic drift over time and maintain
genome sequence of strain B. lactis associated with B. lactis.
strain integrity. DuPont also performs
Bi-07 can be found in GenBank under bacterial identification based on 16s In human clinical studies, B. lactis
the number CP003498. The genomic rRNA gene sequence similarity for Bi-07 has been safely used as a single
variability within the B. animalis every produced batch of probiotics. entity and in combination with other
subsp. lactis is very low and probiotics and/or prebiotics. The age
associated only with single-nucleotide Safe for consumption
of the subjects in these trials ranged
polymorphism (SNP) or with Bifidobacterium spp. has long been
between 7 months (toddlers) and
insertions or deletions of bases considered safe and suitable for
~70 years. Most of the studies were
(INDEL) (Briczinski et al, 2009; Milani human consumption with several
conducted in healthy subjects, but
et al, 2013). However, SNPs and published studies addressing its

2
some also involved subjects with important means of demonstrating hospital-acquired infections and are
atopic dermatitis, functional bowel the potential of an organism to be refractory to treatment. The
disorders, or infections requiring readily inactivated by the antibiotics transmissible nature of genetic
antibiotic treatment. No serious used in human therapy. Antibiotic elements that encode vancomycin
adverse effects have been associated resistance is a natural property of resistance in these enterococci is an
with the administration of B. lactis microorganisms and existed before important mechanism of
Bi-07. antibiotics became used by humans. pathogenicity.
In many cases, resistance is due to the
The safety of formulas containing Resistance to vancomycin in certain
absence of the specific antibiotic
probiotics and prebiotics as well as lactobacilli, pediococci, and
target or is a consequence of natural
fecal microbiology and colonization of leuconostoc is due to intrinsic factors
selection. Antibiotic resistance can be
the probiotic was evaluated in a related to the composition of their cell
defined as the ability of some bacteria
multicenter, double-blind, placebo- wall. It is not due to any transmissible
to survive or even grow in the
controlled, randomized study with elements (Delcour et al, 1999). B. lactis
presence of certain substances that
healthy toddlers, 12-34 months of age. Bi-07 is vancomycin-sensitive.
usually inhibit or kill other bacteria.
Toddlers were randomly divided into This resistance may be inherent/ A tetracycline resistance gene
three groups: control, probiotic (B. intrinsic or acquired. common for B. lactis is also present in
lactis Bi-07), and synbiotic (B. lactis
the B. lactis Bi-07 genome in a stable
Bi-07 and fructo-oligosaccharide, FOS). Inherent or intrinsic resistance
genomic location suggesting unlikely
B. lactis was detected significantly Most, if not all, strains of a certain
gene transferal or alteration in
more frequently in the feces of the bacterial species are not normally
phenotypic activity (Stahl and
probiotic and synbiotic group at days 7 susceptible to a certain antibiotic.
Barrangou, 2012). To date, antibiotic
and 28, compared to the control group. The antibiotic has no effect on these
resistance transfer cases have not
No significant differences were found cells, being unable to kill or inhibit
been reported for Bifidobacterium
in fecal concentrations of Bacteroides, the bacterium, for example because
used in foods and feed. Measurements
Streptococcus, or total Bifidobacterium the target for the antibiotic may
of antibiotic sensitivity did not
groups. There were no statistically be missing.
demonstrate resistance for B. lactis
significant differences across formula
Acquired resistance Bi-07 at levels exceeding any
groups in the numbers and kinds of
Most strains of a bacterial species are breakpoints defined by EFSA (Morovic
formula-related adverse effects
usually susceptible to a given et al, 2017). The expressed level of
(Bettler et al, 2006).
antibiotic. However, some strains may tetracycline resistance in B. lactis Bi-07
To investigate the safety and be resistant, having adapted to is, however, equal to the EFSA cut-off
tolerability B. lactis Bi-07 in survive antibiotic exposure. Possible value (EFSA, 2012). The antibiotic
conjunction with defined clinical explanations for this include: susceptibility patterns (antibiogram)
end-points, a cohort of healthy active for B. lactis Bi-07 are summarized in
• a mutation in the gene coding for
adults from the trial by West et al Table 1.
the antibiotic’s target can make an
(West et al, 2014b) was analyzed for
antibiotic less efficient. This type of Production of biogenic amines
routine hematology and clinical
antibiotic resistance is usually not Histamine and tyramine are biogenic
chemistry markers. Supplementation
transferable. amines that occur naturally in a wide
with a combination of L. acidophilus
• a resistance gene may have been range of foods including fermented
NCFM and B. lactis Bi-07 (5 × 109 CFU of
acquired from another bacterium. products. They are formed by the
each strain) had no impact on these
enzymes present in the raw material
markers (Cox et al, 2014). This data Of the acquired resistances, the latter or are generated by microbial
provides evidence supporting the use is of most concern, as it may be decarboxylation of amino acids. The
of this probiotic supplement over a passed on to other bacteria; including consumption of food containing large
period of 5 months in healthy active potentially pathogenic ones. amounts of these amines can induce
adults without obvious safety or
Much concern has arisen in recent adverse reactions such as nausea,
tolerability issues.
years regarding vancomycin headaches, rashes, and changes in
Antibiotic susceptibility patterns resistance. Vancomycin-resistant blood pressure (Ladero et al, 2010).
Antibiotic susceptibility profiles are an enterococci are a leading cause of

3
Table 1. B. lactis Bi-07 antibiotic susceptibility profiles
Antibiogram of B. lactis Bi-07 was established using ISO 10932 IDF223 method and VetMIC Lact-1 and 2 micro-dilution plates that include all
antibiotics that are recommended by The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Recorded Minimum
Inhibitory Concentrations (MICs) are displayed in the table below. All MIC values are below or equal to the Microbial Break Points (MBPs) defined
for Bifidobacterium (EFSA Journal 2012;10(6):2740). According to the results B. lactis Bi-07 does not bear acquired antibiotic resistance (Morovic et al,
2017).

Chloramphenicol
Erythromycin
Streptomycin

Clindamycin

Vancomycin
Tetracycline
Gentamycin

Kanamycin

Ampicillin
Gm Km Sm Tc Em Cl Ch Amp Va

Max MIC μg/ml

Bifidobacterium animalis Bi-07 64 256 64 8 0.12 <0.03 2 0.25 0.5

MBP for Bifidobacterium** 64 NR*** 128 8 1 1 4 2 2

**EFSA Journal 2012;10(6):2740.

NR***: not required

In lactic acid bacteria, production of In humans, animals, plants and that probiotics have to be consumed
histamine results from the catabolism microorganisms, L(+)-lactic acid is a in sufficient numbers to provide the
of histidine by a histidine normal intermediate or end product of desired health benefit. It is likely that
decarboxylase, and production of the carbohydrate and amino acid different strains and different effects
tyramine results from the catabolism metabolic processes whereas, D(-)- require different dosages.
of tyrosine by tyrosine decarboxylase. lactic acid was thought to be “non-
Delivering the proper dose of B. lactis
A specific detection method for physiological” and a possible cause for
Bi-07 over the shelf-life of a product
histidine and tyrosine decarboxylase lactate acidosis.
can be dependent on many factors
genes has been developed internally
Although some species of probiotic such as formulation, processing,
to DuPont based on the scientific
cultures, as nutritional ingredients packaging, and storage temperature
literature and on the most updated
that may produce D(-)-lactic acid, have and humidity. It is important to
genomic databases. With this method,
been safely administered to infants consider these factors and run
no histidine or tyrosine decarboxylase
(Connolly et al, 2005), Codex specifies stability trials to develop sound
gene was identified in B. lactis Bi-07
that only L(+)-lactic acid producing products.
genome (Morovic et al, 2017).
cultures can be used for infant
Consequently, B. lactis Bi-07 is unlikely Health-related properties
formula and follow up formula. B.
to produce histamine or tyramine. B. lactis Bi-07 has been extensively
lactis Bi-07 only produces L(+)-lactic
studied for its health sustaining or
L/D-lactic acid production acid (Table 2).
promoting effects. The mechanisms
Lactic acid is the most important
Product Stability of action have been demonstrated in
metabolic end product of fermentation
Today there is a general consensus animal models and the efficacy of
processes by lactic acid bacteria and
other microorganisms. Lactic acid
Table 2. L/D Lactic acid production
fermentation has been used for
thousands of years in the production L/D Lactic acid production
of fermented foods. Due to its
molecular structure, lactic acid has 100/0
L/D lactic acid production
two optical isomers. One is known as molar ratio
Boehringer Mannheim/R-Biopharm UV-method
L(+)-lactic acid and the other, its mirror
image, is D(-)-lactic acid. Source: DuPont internally-generated data

4
B. lactis Bi-07 has been further Figure 2. Stability of B. lactis Bi-07 culture concentrate.
evaluated in human clinical trials. n 4°C n 25°C n 30°C
Clinical trials to date have shown that 1012
B. lactis Bi-07 has been included in
probiotic studies to understand its
potential role in resistance to
respiratory and gastrointestinal (GI) 1011

Log CFU/g
infections, functional intestinal
symptoms, and the remedy of and
incidence of symptoms of antibiotic
1010
associated diarrhea. Studies have
been conducted by using B. lactis
Bi-07 as a single strain or in
combination with other probiotic 109
0 3 6 9 12 15 18 21 24 27 30 33 36
strains and/or prebiotics. The key
Time (months)
findings of this research are
summarized below. Source: DuPont internally-generated data

certain genera, including Lactobacillus Resistance to acid and bile and

Benefits to intestinal health and and Bifidobacterium, is generally survival in the intestinal passage
well-being thought to be associated with a According to the generally accepted
The human GI tract is an extremely healthier GI tract. definition of probiotics, a probiotic
complex ecosystem and represents microorganism should be viable at the
the host’s greatest area of contact The resident microbes are involved in
time of ingestion to confer health
with the environment. This ecosystem many metabolic processes, such as
benefit. A variety of traits are believed
comprises: the fermentation of undigested
relevant for surviving passage through
carbohydrates into short-chain fatty
the GI tract, the most important of
• the gastrointestinal epithelium acids, lipid metabolism, and vitamin
which is tolerance to the highly acidic
• immune cells synthesis. Another important function
conditions present in the stomach and
• resident microbiota of the intestinal microbiota is to
to the concentrations of bile salts
stimulate the maturation of the
The primary function of the human GI found in the small intestine.
immune system and provide
tract has long been considered to be
protection against incoming, In vitro studies have shown that B.
the digestion and absorption of
potentially pathogenic microbes. lactis Bi-07 is resistant to low pH
nutrients and the excretion of waste
conditions and has a good survival rate
end-products. In recent years, When the delicate ecological balance
in the presence of bile at the
however it has become recognized of this highly complex microbial
concentrations present in the
that the GI tract fulfills many other community is disturbed by
duodenum (Ding and Shah, 2007;
functions, which are essential to our environmental or physiological factors,
DuPont, Internally generated data)
well-being. The GI tract harbors a vast predisposition to infectious and
(Table 3). Accordingly, B. lactis Bi-07
number of microbial cells (1014), which immuno-inflammatory diseases is
consumption elevates B. lactis counts
may surpass the number of cells that enhanced. It may then become
in feces during consumption (Bettler et
make up the human body (Sender et necessary to re-establish a beneficial
al, 2006; Childs et al, 2014; Forssten et
al, 2016). microbiota. Research has shown that
al, 2014; Larsen et al, 2011; Ringel-Kulka
specific probiotic strains can be used
The intestinal microbiota is estimated et al, 2011) suggesting survival of
to optimize the composition and
to consist of at least 1000 species, gastrointestinal passage by the strain.
activity of the intestinal microbiota
although 95-99% of all bacteria belong
and, thus, to reduce the risk for a range Adhesion to intestinal mucosa
to just 10 genera. Many members of
of diseases or unfavorable conditions While adhesion is not a pre-requisite
the intestinal microbiota are beneficial,
(Guarino, 2013; Lin et al, 2014; for a strain to elicit probiotic
while others are potentially
Ouwehand, 2006; Scott et al, 2015). properties, interaction with the
detrimental or their function not
intestinal mucosa is considered
known. A higher concentration of

5
important for a number of reasons. Table 3. Acid and bile tolerance of B. lactis Bi-07
Binding to the intestinal mucosa may
Survival in GI tract conditions in vitro
prolong the time a probiotic strain
can reside in the intestine. This
++ 7 0-79% survival in hydrochloric acid and 1% pepsin at
interaction with the mucosa brings Acid tolerance
pH 3.5 for 1h at 37°C
the probiotic in close contact with the
intestinal immune system, giving it a
Bile salt tolerance ++ 70-79% survival in 0.3% bile salt-containing medium
better opportunity to modulate the
immune response. It may also protect
against enteric pathogens by limiting ++++ Excellent +++ Very good ++ Good + Fair

their ability to colonize the intestine.

B. lactis Bi-07 has been demonstrated Source: DuPont internally-generated data

to adhere to human epithelial cell

lines (Caco-2 and HT-29; Table 4) and
to human colonic mucus (Table 5) in Table 4. Adherence of B. lactis Bi-07 to human intestinal cells in vitro
vitro.
In vitro adhesion to intestinal epithelial cells
Similar results were observed in a
study that evaluated bacterial
HT-29 ++
adhesion to Caco-2 cells, either by
using radio-labelled bacteria and
counting Caco-2-bound radioactivity Caco-2 +++
(radioactive adhesion assay), or by
quantifying Caco-2-bound bacteria ++++ Excellent +++ Very good ++ Good + Fair
with genus or species-specific primers
via real-time PCR (non-radioactive Source: DuPont internally-generated data
adhesion assay). The study found that
the Caco-2 cell adhesion activity of
seven bifidobacterial strains, Table 5. Adherence of B. lactis Bi-07 to human colonic mucus in vitro
belonging to 5 different species,
varied considerably. B. lactis Bi-07 was Adherence of B. lactis Bi-07 to human colonic mucus in vitro

one of the two most adhesive strains

Measured by fluorescence labelling of bacteria.
(Candela et al, 2005).
Adhesion rate [%] is calculated comparing the fluorescence of
3.8% ++++
the adhered bacterial cells with the fluorescence of labelled
Intestinal bacteria must make their
bacteria applied.
way through the mucosal layer before
attaching to cell surface. The + poor (< 0.5) ++ fair (0.5 - 2%) +++ good (2 – 3.5%)
extracellular glycocalyx matrix and ++++ very good (3.5-5%) +++++ excellent (> 5%)
mucins are made mostly of
proteoglycans that are susceptible to Source: DuPont internally-generated data
enzymatic degradation. Many
pathogens such as streptococci and 2001). Candela et al showed that B. and results in more avid binding to
staphylococci, as well as non- lactis Bi-07 uses enolase as a surface Caco-2 cells (Candela et al, 2007;
pathogenic bifidobacteria, capture receptor for human plasminogen and Candela et al, 2008a; Candela et al,
plasminogen on their outer surface. that B. lactis Bi-07 can acquire 2008b).
Plasminogen is a proenzyme that is plasminogen from crude extracts of
The identification of five putative
converted to plasmin by tissue type human feces (Candela et al, 2009;
plasminogen-binding proteins among
plasminogen activator or urokinase. Candela et al, 2011). It was also shown
the cell wall fraction of B. lactis Bi-07,
The best-known function of plasmin is that plasminogen bound to B. lactis
suggest that plasminogen binding to
the degradation of fibrin clots, but its Bi-07 can be converted into active
B. lactis is due to the concerted action
protease activity also extends to plasmin and this increases migration
of a number of proteins located on
proteoglycans (Lähteenmäki et al, of B. lactis Bi-07 through fibrin-matrix
the bacterial cell surface. These
6
Table 6. B. lactis Bi-07 pathogen inhibition in vitro towards these enteropathogens.

B. lactis Bi-07 pathogen inhibition in vitro In exclusion studies, the adhesive

bifidobacterial strains excluded Y.
enterocolitica. Only one strain of B.
Salmonella Typhimurium +
bifidum exerted exclusion activity
towards S. enterica serovar
Staphylococcus aureus + Typhimurium, and no bifidobacteria
strain excluded E. coli H1040.
Escherichia coli +++ Enteropathogens excluded none of the
bifidobacterium strains in the
exclusion assays. These results show
Listeria monocytogenes +
the ability of B. lactis Bi-07 to compete
with pathogens for epithelial
++++ Excellent +++ Very good ++ Good + Fair
monolayer adhesion, which plays a
possible role in protecting against, or
Source: DuPont internally-generated data
recovery from, pathogen colonization
(Candela et al, 2005).
findings represent a step forward in other substances that act as antibiotic
understanding the mechanisms agents and as competition for B. lactis Bi-07 was shown to prevent
involved in Bifidobacterium-host nutrients. It should be pointed out, inflammation-dependent dysbiosis on
interaction (Candela et al, 2007; however, that the extrapolation of HT-29 cell line treated with fecal slurry
Candela et al, 2008c). such results to the in vivo situation is collected from healthy young adults
not straightforward. The assessment in (Centanni et al, 2014). B. lactis Bi-07
Inhibition of pathogens Table 6 is based on such an in vitro reduced the over-growth of pathogens
The protective role of probiotic assay. such as members of Fusobacteriaceae,
bacteria against gastrointestinal
Bacillaceae, and Enterococcales on the
pathogens is highly important to One in vitro study investigated how
enterocyte surface. Tumor necrosis
therapeutic modulation of the enteric various bifidobacteria, including B.
factor (TNF)-α-induced inflammation
microbiota. Probiotics are able to lactis Bi-07, and adhesive
increased the growth of bifidobacteria
inhibit, displace, and compete with enteropathogens (Salmonella enterica
in vitro proposedly due to an adaptive
pathogens, although these abilities are serovar Typhimurium, Yersinia
response to maintain microbiota
strain-dependent. The probiotic strains’ enterocolitica, and Escherichia coli
homeostasis. Results suggest a
putative mechanisms of action against H10407) compete for adhesion to
beneficial effect of B. lactis Bi-07 in the
pathogenic microorganisms include Caco-2 cells (Candela et al, 2005). Two
treatment of intestinal inflammation
the production of inhibitory competition conditions, displacement
and in the prevention of dysbiosis.
compounds, competition with and exclusion, were tested for each
pathogens for adhesion sites or bifidobacterium-enteropathogen pair. Prebiotic utilization
nutritional sources, inhibition of the Prebiotics are food ingredients that are
In the displacement assay, the
production or action of bacterial non-digestible for humans, but are
enteropathogen was added to the
toxins, ability to co-aggregate with utilized by bacteria in the intestine.
Caco-2 cell monolayer before the
pathogens, and the stimulation of the Prebiotics have been shown to
addition of the bifidobacterium. In the
immune system. maintain balance in the gut microbiota
exclusion assay, the bifidobacteria
by promoting growth of some strains
In vitro inhibition is usually were added to the Caco-2 cell
of bifidobacteria and lactobacilli,
investigated using an agar inhibition monolayer before the addition of the
whereas pathogens have in general
assay, where soft agar containing the enteropathogen. At the end of both
more restricted carbohydrate
pathogen is laid over colonies of competition assays, the
metabolism. Most commonly used
probiotic cultures, causing the bifidobacterium and enteropathogen
prebiotics are complex
development of inhibition zones cells bound to Caco-2 cells were
oligosaccharides like fructo-
around the colonies. This effect may specifically quantified using real-time
oligosaccharides (FOS) and galacto-
be due to the production of acids, PCR. All the bifidobacterial strains
oligosaccharides (GOS).
hydrogen peroxide, bacteriocins, and showed strong displacement activity

7
B. lactis Bi-07 can utilize panose, Figure 3. The probiotic mixture containing B. lactis Bi-07 protects the fecal microbiota from
disruption by antibiotics, as indicated by the greater dissimilarity of the microbiota of the placebo
sophrose, FOS, gentobiose, and
group compared to the baseline microbiota composition (Adapted from: Engelbrektson et al, 2006).
xylo-oligosaccharides (XOS) of
110 Probiotic Placebo
different lengths as a carbon source
in vitro (Mäkeläinen et al, 2009; 100

% similar to baseline microbiota levels

Mäkeläinen et al, 2010b). The growth
rates were close to those achieved 90
with glucose. Some growth of B. lactis
80
Bi-07 was also observed with GOS,
polydextrose, lactitol, and pullulan as 70
substrates. Xylan did not induce
growth. For XOS it was later shown 60
that they enhance the growth of B.
50
lactis (not specifically Bi-07) in colon
simulator that used human feces as
40
an inoculum (Mäkeläinen et al, 2010a).
30
Antibiotic associated diarrhea and Baseline Immediately after 4 days post- 13 days post-
stabilization of microbiota during antibiotic treatment antibiotic regime antibiotic regime
antibiotic treatment
B. lactis Bi-07 was included in a
five-strain formulation investigated
for its ability to stabilize the intestinal Figure 4. The probiotic mixture containing B. lactis Bi-07 promotes the maintenance of bifidobacteria
levels in the feces of antibiotic-consuming subjects during post-treatment (*p=0.030) (Adapted from:
microbiota during and after antibiotic
Engelbrektson et al, 2006).
therapy (Engelbrektson et al, 2006). In
this human trial of patients taking 140 Probiotic Placebo
Bifidobacterium counts compared to baseline

antibiotics, the probiotic product was

120
found to reduce the disturbance of
the total microbiota population 100
(Figure 3). In addition, the probiotic
product still maintained bifidobacteria 80
at significantly higher levels than that
60
of the placebo group even two weeks
after the cessation of antibiotic * * *
40
therapy (Figure 4).
20
B. lactis Bi-07 was evaluated in a
double-blind, placebo-controlled, 0
randomized human clinical study as Baseline Immediately after 4 days post- 13 days post-
antibiotic treatment antibiotic regime antibiotic regime
part of a three-strain formulation (also
including L. reuteri and L. acidophilus
NCFM). A total of 243 children aged colleagues (2006 and 2009; mixture during the antibiotic course (3 to 14
12-36 months were recruited. During including B. lactis Bi-07) were days) and for 7 days thereafter. The
the 14-week intervention period, a evaluated in a large clinical trial with incidence of antibiotic associated
statistically significant reduction in the 503 hospitalized patients subjected to diarrhea (AAD) was significantly
incidence and episodic frequency of antibiotic treatment (Ouwehand et al, decreased with the higher dose. For
diarrhea was recorded in the probiotic 2014). The trial was designed as a B. lactis Bi-07, a dose response effect
versus the placebo group (Ruiz- placebo-controlled dose-response was seen in positively impacting
Palacios et al, 1999). study with randomization stratified symptoms of AAD with daily doses of
according to age, length of antibiotic 1.70 x 1010 CFU and 4.17 x 109 CFU of a
Four strains from the probiotic treatment and gender. The patients multi-strain product applied.
mixture studied by Engelbrektson and consumed the probiotic mixture Incidence of Clostridium difficile

8
associated diarrhea (CDAD) and showed a trend for more efficient patients with pre-existing abdominal
diarrhea-associated symptoms (fever, reduction in the number of days with pain benefited from probiotics in
abdominal pain, bloating, severity and abdominal pain, but the study was not number of pain days.
length of diarrhea) were also reduced sufficiently powered for evaluating
Beneficial modulation of the
in a dose-responsive manner the clinical outcome.
immune system
(Ouwehand et al, 2014).
Bowel function The human immune system is a highly
Forssten and co-workers analyzed Constipated women were evaluated efficient and complex system for
whether the resilience of the GI according to Rome III criteria before defending the body against foreign
microbiota during antibiotic and after a 30-day open-labelled infectious agents (bacteria, viruses,
consumption is enhanced with intervention with B. lactis Bi-07 and parasites) as well as from
probiotics (Forssten et al, 2014). Eighty containing fresh cheese. They malignant cells and other noxious
volunteers had a 7-day course of consumed 30g of fresh cheese daily agents. An immune system that
amoxicillin and clavulanate and were with 108 CFU of B. lactis Bi-07 per functions optimally is an important
randomized to receive a concurrent serving in the active product. The safeguard against infectious and
two-strain probiotic (L. acidophilus probiotic cheese was found to non-infectious diseases. The GI tract is
NCFM and B. lactis Bi-07 at 12.5 x 109 alleviate constipation and the body’s largest immune organ,
CFU/d each) or placebo constipation-related symptoms more containing an estimated 80% of all
supplementation ongoing for a total efficiently than plain fresh cheese, but antibody-producing cells. The
of 14 days. The microbiomes both groups responded to treatment intestinal microbiota represents one of
remained essentially stable in both (Favretto et al, 2013). the key elements in the body’s
groups except for an elevation of immune defense system (Calder et al,
Ringel-Kulka et al studied
supplemented species within the 2013).
combination of L. acidophilus NCFM
treatment group. This was in line with
and B. lactis Bi-07 versus placebo for The immune system of a newborn is
the symptom assessment during the
the symptoms of bloating in patients functionally immature. Exposure to
trial which revealed only mild GI
with functional bowel disorders in a antigens during early life is essential to
symptoms due to the antibiotic
double-blind study (Ringel-Kulka et al, drive the development of the gut
treatment and no statistically
2011). The global relief of GI symptoms mucosal immune system and to
significant differences in symptom
and satisfaction with treatment was maintain immune homeostasis.
scores between the probiotic and
not affected, but bloating symptoms Microbial antigens derived from the
placebo groups.
were significantly reduced in intestinal microbiota and the
Irritable Bowel Syndrome, IBS treatment group. environment play a crucial role in the
Intestinal pain is one of the maturation of gut-associated lymphoid
D’Souza and colleagues studied the
symptoms of IBS. As L. acidophilus tissue and normal resistance to
effects of combination of L.
NCFM is known to induce analgesic disease. Reduced microbial exposure
acidophilus NCFM and B. lactis Bi-07
receptors in rats (Rousseaux et al, in Western societies has also been
versus placebo on the length of days
2007), Ringel-Kulka and colleagues associated with an increased incidence
to resolution of bloating, abdominal
analyzed the gene expression levels of atopic and autoimmune disorders
pain, and altered bowel function in
of mu-opioid receptor (MOR) and (Calder et al, 2013, Versini et al, 2015).
patients who undertook colonoscopy
cannabinoid receptor 2 (CB2) from
in a double-blind trial (D’Souza et al, There is a significant amount of
human mucosal biopsies (Ringel-
2015). A total of 320 patients were evidence to suggest that specific
Kulka et al, 2014). Twenty female
randomized post-colonoscopy to the probiotic strains are able to stimulate
subjects consumed B. lactis Bi-07 in
trial. Patients in the L. acidophilus and regulate several aspects of
combination with L. acidophilus
NCFM+B. lactis Bi-07 group had a natural and acquired immune
NCFM or only L. acidophilus NCFM
significantly lower number of pain responses. This could either be
for 21 days prior to donating biopsies
days following colonoscopy when through stimulation of the gut
during sigmoidoscopy. The L.
compared with the placebo group. immune system or modulation of
acidophilus NCFM alone enhanced
There was no difference in bloating or immune cell production and function
MOR expression whereas the
return to normal bowel habit days. (Lei et al, 2015).
combination product had no effect.
Subgroup analysis revealed that
The combination product, however,

9
Probiotic bacteria with the ability to Figure 5. Induction of IL-10 and IL-12 by B. lactis Bi-07 in PBMCs, compared with Lc. lactis and E. coli
modulate certain immune functions (Adapted from: Foligne et al, 2007).

may improve the response to oral 1800 IL-10 IL-12

1000
vaccination, shorten the duration or 1600 900
reduce the risk of certain types of 1400 800
infection, or reduce the risk of or 700
1200
alleviate the symptoms of allergy and 600

pg/ml

pg/ml
1000
other immune-based conditions 500
800
(Duerkop et al, 2009, Hardy et al, 2013). 400
600
300
Modulation of the immune system is 400
200
an area of intense study in relation to 200 100
the DuPont™ Danisco® range of 0 0
Bi-07 Lc. lactis E. coli Bi-07 Lc. lactis E. coli
probiotics. The goal is to understand
how each strain contributes to the
maintenance and balance of optimal lactis, B. lactis Bi-07 induced moderate Figure 6. Cytokine response to bacterial DNA
amounts of IL-10. However, B. lactis (cultured with PBMC) compared with the
immune function. The immune
response to LPS (Adapted from: Lammers et
system is controlled by compounds Bi-07 induced higher excretion of IL-12
al, 2003).
known as cytokines. Cytokines are from PBMCs (Figure 5). This is known
hormone-like proteins made by cells to shift the immune system towards a 4500

that affect the behavior of other cells so called Th1 type of response, which 4000

and, thereby, play an important role in plays a key role in, for example, 3500

IL-10 pg/10E6 PBMC

the regulation of immune system warding off tumors and viruses, and 3000
functions. Cytokine expression can be antagonizes allergic response (Foligne 2500
modulated by specific probiotic et al, 2007).
2000
bacteria. However, interpreting the Another study including B. lactis Bi-07, 1500
health relevance of changes in investigated whether bacterial DNA 1000
cytokine levels, both from in vivo and plays a role in the immunomodulatory 500
human studies, remains a challenge. effects of probiotic treatment. PBMCs 0
LPS Bi-07
Expression of cytokines and other from healthy donors were incubated
immune markers with pure DNA from probiotic strains.
Figure 7. Percentage of protection in an
In vitro assays are widely used to Cytokine production was analyzed in acute murine model of inflammation (TNBS)
define the cytokine profiles of culture supernatants. It was shown (Adapted from: Foligne et al, 2007).
probiotics and, thereby, determine that the DNA of B. lactis Bi-07
stimulated the secretion of IL-10, 50
their immunological effects. By
measuring the impact of probiotic exceeding the IL-10 levels induced by 40

bacteria during interaction with lipopolysaccharide (LPS) (Figure 6)

30
(Lammers et al, 2003). These results
% protection

cytokine-expressing peripheral blood

mononuclear cells (PBMCs), indicate the IL-10 inducing effect of 20

information is generated that can whole cells differs from that of DNA. 10
help determine the ability of each It also suggests that, even when cells
0
strain to contribute to balanced die and their DNA is released, they
immune health. may modulate the immune system. -10

-20
B. lactis Bi-07 was investigated in vitro B. lactis Bi-07 has demonstrated an Bi-07 Lc. lactis E. coli

for its ability to induce the PBMCs to ability to modulate the immune
secrete selected cytokines: system in an intestinal inflammation inflammation. B. lactis Bi-07 exerted
interleukin (IL)-10 and IL-12. The results animal model, adding on its ability to moderate but significant protection
were compared with a strain of contribute to a balanced immune from the intestinal inflammation in
Lactococcus (Lc.) lactis and a strain of system. Figure 7 demonstrates the this model, demonstrating its ability
non-pathogenic E. coli. Similar to Lc. percentage of protection from a to interact with and balance the
chemically-induced intestinal

10
intestinal mucosal immune response article, Bi-07 is called B. infantis due to species show quantitative and
(Figure 7) (Foligne et al, 2007). an identification mistake at the time. qualitative differences in their
The authors describe the strain as “a possible biotherapeutic effects
Protection from experimental human isolate obtained from Rhone- (Wagner et al, 1998).
Candida albicans infection Poulenc, Madison, Wisconsin” that
Candida yeasts are usually present in Another study has looked at the
indicates the strain origin and the
most people but uncontrolled effect of prior colonization with
strain being Bi-07. It was seen that
overgrowth, for example due to probiotic bacteria on the antibody
both bifidobacteria prolonged the
medication or underlying disease, can responses of immunodeficient mice
survival of C. albicans-colonized adult
lead to candidiasis. Candidiasis is a subject to alimentary tract
and neonatal mice. Mice diassociated
fungal infection (mycosis), caused by colonization with C. albicans.
with C. albicans and B. lactis Bi-07 or
species of the genus Candida, Although the probiotic bacteria did
the other B. lactis strain had
predominantly Candida albicans. not induce a vigorous antibody
significantly fewer C. albicans in their
Candidiasis encompasses infections response to their own antigens, the
stomachs and intestines compared
that range from superficial, such as study demonstrated that they altered
with mice monoassociated with C.
oral thrush and vaginitis, to systemic the antibody response to C. albicans
albicans. The presence of either of the
and potentially severe diseases. The in mice. The authors observed mixed
two B. lactis strains in the alimentary
increased incidence of Candida immunomodulatory effects from the
tract reduced the incidence of
infections and their increasing probiotic bacteria. The probiotic
disseminated candidiasis in mice. Less
resistance to antifungal antibiotics strains induced antibody responses to
systemic candidiasis of endogenous
provides a strong impetus for new some C. albicans antigens but
origin in mice was detected in mice
research efforts to explore the use of inhibited antibody responses to
colonized with B. lactis Bi-07 rather
probiotic bacteria for the prophylaxis others. However, the data indicate
than the other strain of B. lactis.
and therapy of candidiasis. that probiotic bacteria (such as L.
Immune responses were evaluated as
acidophilus NCFM and B. lactis Bi-07),
B. lactis Bi-07 has been evaluated in a immunoglobulins in the sera of mice
which effectively prolonged the
Candida infection model for its either monoassociated with one of
survival of immunodeficient mice
capability to protect immunodeficient the bifidobacteria or C. albicans or
colonized with C. albicans (Wagner et
mice from lethal candidiasis (Wagner diassociated with one of the
al, 1997), also strongly stimulated the
et al, 1997). Here the strain was found bifidobacteria and C. albicans.
production of antibodies to C. albicans
to reduce the level of Candida Both bifidobacteria affected the antigens. These results suggest that
colonization in all parts of the production of antibodies to C. commensal bacterial flora should be
gastrointestinal tract and significantly albicans, but the effects were considered an important component
reduce the incidence and severity of different for the two mouse types and of the humoral immune system in
candidiasis in mice. Furthermore, the the two bifidobacterial strains. protecting against candidiasis. They
study showed higher total levels of Despite these differences, both also demonstrate that the presence
IgA, IgG, and IgM and an improved mouse types monoassociated with B. of certain probiotic bacteria can
specific antibody response. In lactis Bi-07, but not the other B. lactis, enhance or suppress antibody
addition, B. lactis Bi-07 induced a had increased serum IgG, IgA, and responses to antigens administered
stronger cell-mediated immune IgM compared with sera from germ- via the mucosal surfaces of the
response against Candida. As a result, free (GF) controls. Additionally, in both alimentary tract (Wagner et al, 2000).
the lethality of the candidiasis was types of mice diassociated with C.
significantly reduced in both adult Modulation of the immune system
albicans and B. lactis Bi-07, the levels
and new-born mice. in humans
of IgG, IgA, and IgM were higher
Effects of B. lactis Bi-07
A further study evaluated the compared to the GF control sera. The
supplementation with or without GOS
capacity of two B. lactis strains, B. two bifidobacteria strains also
on immune cell activity and intestinal
lactis Bi-07 and B. lactis Bb-12, to suppressed weight loss associated
microbiota of elderly individuals was
protect two types of immunodeficient with C. albicans infection. The results
evaluated in a double-blind
mice from orogastric candidiasis and show that B. lactis Bi-07 can provide
randomized placebo-controlled
systemic candidiasis of endogenous important protection against
cross-over trial (Maneerat et al, 2013).
origin (Wagner et al, 1998). In the candidiasis in immunodeficient mice
During the trial subjects consumed
and that different strains of the same

11
the investigational product for 21 days lactis Bi-07. Supplementation with B. pronounced with L. acidophilus
with a 28-day wash-out period in lactis Bi-07 or the placebo started on NCFM+B. lactis Bi-07 than L.
between each treatment period. All day 0 and continued for 21 days. The acidophilus NCFM alone and
subjects consumed all four treatments subjects consumed two capsules per therefore the investigators speculated
(B. lactis Bi-07; GOS; B. lactis Bi- day with 1010 CFU B. lactis Bi-07 or two that B. lactis Bi-07 might give
07+GOS; placebo), but due to carry- capsules per day with maltodextrin additional advantage for immune
over effects only the first treatments’ (control). On day 7 and 14, the subjects defense against infections (Leyer et
samples were analyzed statistically as received the oral vaccine. Blood al, 2009).
if the study was designed for parallel samples were collected on day 0, 21,
The same probiotic combination (L.
groups. Phagocytosis and oxidative and 28, and antigen-specific
acidophilus NCFM+B. lactis Bi-07) was
burst capacity of monocytes and antibodies IgG (immunoglobulin G)
tested for enhanced resilience against
granulocytes, cytokine and chemokine were determined. Supplementation
URTI and GI illness among physically
concentrations, composition of fecal with B. lactis Bi-07 showed the
active adults in a randomized
microbiota, and intestinal organic acid tendency to increase specific IgG
placebo-controlled intervention trial
levels were determined. It was found induction compared to the placebo
with three parallel groups consuming
that phagocytic activity of monocytes group. This indicates the stimulation
L. acidophilus NCFM+B. lactis Bi-07, B.
and granulocytes was enhanced, but of specific immunity by B. lactis Bi-07
lactis Bl-04, or placebo (West et al,
intracellular reactive oxygen species (Figure 8) (Paineau et al, 2008).
2014b). During the wash-out period
were not elevated. The results indicate
and following the 150-day
that B. lactis Bi-07 augments
Figure 8. Relative change in specific IgG consumption, the number of illness
phagocytosis but not inflammation
titre in orally vaccinated humans after episodes and duration were recorded
that could be harmful on homeostatic
supplementation with B. lactis Bi-07 (Adapted and ranked according to a categorical
situation (Maneerat et al, 2013).
from: Paineau et al, 2008). subjective estimate. B. lactis BI-04
As to effects on immune markers, XOS was associated with a significant
influenced the cell-surface markers of 125 n Maltodextrin (control) reduction of risk of URTI whereas the
n B. lactis Bi-07
natural killer T cells and suppressed 120 combination product (L. acidophilus
IL-10 secretion, B. lactis Bi-07 lowered 115 NCFM+B. lactis Bi-07) only showed a
IL-4 secretion and IgA levels while trend towards effectiveness. There
% change

110
enhancing IL-6 secretion, and the were too few GI illness episodes for
105
synbiotic supplementation altered statistical analyses. However, no clear
100
B-cell surface markers. No significant effects were seen in innate immune
effects were seen on phagocytosis, 95 markers including 34 cytokines, white
oxidative burst, or leukocyte counts. 90 cell differentials, and natural killer
0 21 28
No clear conclusions could be made days
(NK) cell and PBMC activity, that
on mechanisms of immune effects of would explain enhanced resilience
treatments, but XOS and B. lactis Bi-07 towards URTI (West et al, 2014a).
were suggested to present an Impact on respiratory health
The beneficial effect of probiotic
immunostimulatory effect potentially The impact of a combination of B.
combination (L. acidophilus NCFM+B.
beneficial for subjects with suppressed lactis Bi-07 and L. acidophilus NCFM
lactis Bi-07) evidenced in the previous
Th1 response (elderly) or excessive Th2 on respiratory health was investigated
study was evaluated further. PBMCs
activity (atopic) (Childs et al, 2014). in a randomized placebo controlled
were isolated to examine whether
study of 326 Chinese children, 3-5
The ability of B. lactis Bi-07 to probiotic consumption had affected
years of age. Intake of two doses of L.
stimulate specific immunity has been the frequency of circulating
acidophilus NCFM+B. lactis Bi-07 daily
evaluated in a human study regulatory T (Treg) cells (West et al,
for 6 months significantly reduced the
measuring primary immune reaction 2016). CD4+ T-cells were analyzed for
incidence and duration of upper
following vaccination. Human CD127loCD25+ surface-stained markers
respiratory tract infection (URTI)
volunteers were orally vaccinated and CD127loFoxP3+ intracellular-
symptoms and antibiotic use,
using cholera vaccine as a vaccination stained markers to determine the
indicating improved efficacy
model. In addition, they received percentage of Treg-cells. Expression of
compared to a placebo or the single
either a placebo (maltodextrin) or B. CCR9 and CXCR3 was evaluated in
strain alone. The effects were more

12
effector/memory (CD45RO+) and naive SCORAD (scoring atopic dermatitis) groups in relation to the duration of
(CD45RO-) CD4+ T cells and Treg cells clinical evaluation tool resulted in illness or treatment. All three
using the surface-stained samples. significant improvement of scores in supplements were generally well
There were no significant differences B. lactis Bi-07 group (Gobel et al, tolerated. The results suggested that
in CD4+ T-cell or Treg-cell subsets 2010). The levels of Bifidobacterium the use of nutritional supplements
between the L. acidophilus NCFM+B. correlated positively, while the levels containing B. lactis Bi-07 is beneficial
lactis Bi-07 group and the placebo of the Lactobacillus group correlated and safe in children undergoing
group. The intensity of physical negatively with improvement of antibiotic treatment, but its effect in
activity, on the other hand, had atopic eczema evaluated by the preventing infections remains unclear
significant effect on the frequency of atopic dermatitis score (SCORAD) (Schrezenmeir et al, 2004).
Treg-cells. After dividing all the (Larsen et al, 2011). This correlation
A further study – a double-blind,
participants in the probiotics group was observed across the whole study
randomized, 4-month study – was
and the placebo group into tertiles cohort and was not attributed to
conducted at 13 locations in Brazil,
depending on the intensity of exercise probiotic intake.
Mexico, Portugal, and Spain (Fisberg
(low, medium, and high), the authors
Other health-related properties et al, 2002). The objective was to
observed a significant increase in the
Well-being and growth of children evaluate the incidence and duration
frequency of Treg-cells in the samples
Appropriate nutrition is particularly of illness plus anthropometrics in
of medium-intensity group.
important for children during acute children who received a nutritional
Combination of B. lactis Bi-07 and L.
phases of illness to maximize energy supplement with or without
acidophilus NCFM in healthy active
and fluid intake and to improve their synbiotics. Children recruited for the
adults was not associated with
recovery. B. lactis Bi-07 has been study were 1 to 6 years old and
changes in the frequency of circulating
evaluated in synbiotic nutritional underweight (as defined by a World
Treg-cells. However, regular physical
supplements administered to 1 to Health Organization/National Center
activity may have hidden the potential
10-year old children (also including L. for Health Statistics chart (WHO/
influence of probiotic supplementation
acidophilus NCFM and FOS) in two NCHS)), but otherwise healthy.
on circulating Treg-cells (West et al,
human clinical studies (Fisberg et al, Overall, the incidence of sickness,
2016).
2002; Schrezenmeir et al, 2004). A number of sick days, and antibiotic
Atopic dermatitis multicenter, open, randomized, use were similar between the two
In a human clinical trial, children with comparative study included acutely ill groups. However, the subgroup of
atopic dermatitis (AD) (7-24 months children aged 1-6 years who required children aged 3 to 5 years consuming
old) were given B. lactis Bi-07 (n=17), L. antibiotic treatment for a bacterial the synbiotic formula who had at
acidophilus NCFM (n=17), or placebo infection (Schrezenmeir et al, 2004). least one episode of sickness,
(n=16) (Gobel et al, 2010; Larsen et al, The children received either a experienced significantly fewer sick
2011). The fecal numbers of L. synbiotic nutritional supplement, a days. This suggests that the formula
acidophilus and B. lactis increased nutritional supplement without the may help to reduce the duration of
significantly after intervention, synbiotic components, or a fruit- sickness in underweight children. The
indicating survival of the ingested flavored drink with their medication. synbiotic group experienced a
bacteria. The administration of B. Total energy intake, weight gain, and significant reduction in constipation
lactis Bi-07 did not affect the fecal lactobacilli levels were across all ages. All subjects
composition and diversity of the main significantly greater in the group that experienced growth in relation to
bacterial populations in feces. consumed the synbiotic formula. This height, weight and weight/height-
Eosinophil cationic protein, IL-31, group also had the lowest absolute ratio with no differences in growth
interferon (IFN)-γ, IL-10, and IgE (total), rate of relapse or new bacterial between the synbiotic and control
IgE (egg), IgE (milk) were measured infections, but these differences were feeding groups. Both supplements
from plasma and calprotectin from not statistically significant. There were used in the study were well tolerated,
feces. No differences were found in no significant differences in fecal and the overall incidence of adverse
primary clinical or immunological bifidobacteria levels at the end of events was very low (Fisberg et al,
outcomes. In the B. lactis Bi-07 group, antibiotic therapy, although levels 2002). These studies provide further
levels of IFN-γ and IL-10 showed a were higher in the synbiotic nutritional evidence of the safe, beneficial use of
trend towards reduction. However, supplement group. There were also no B. lactis Bi-07 in child nutrition.
post-hoc analysis using subjective significant differences among the

13
Necrotizing enterocolitis in very low B. lactis Bi-07 were characterized as intragastric B. lactis Bi-07 dosages of
birth weight infants orthologues of oxalyl-CoA 109 CFU/ml for 4 weeks and compared
Necrotizing enterocolitis (NEC) is a decarboxylase (oxc) and formyl-CoA with uremic non-treated rats and sham
multifactorial disease that is common transferase (frc) (Turroni et al, 2010). group rats (Wei et al, 2014). The
among preterm infants with very low The results support the use of B. lactis probiotic treatment efficiently reduced
birth weight. The pathogenesis species, such as B. lactis Bi-07, over bacterial translocation during uremia
involves intestinal immaturity, other Bifidobacterium as a potential to the level of non-uremic sham group.
formula feeding, and abnormal maintenance for oxalate homeostasis Similarly, inflammatory markers (IL-6,
microbial colonization. B. lactis Bi-07 CRP, and TNF-α) and intestinal
was examined in a randomized Modulation of adipogenesis permeability were restored to the
double-blind trial where mothers of Evidence implies an association level of non-uremic rats, although
preterm infants were supplemented between gut microbiota and obesity. endotoxin levels did not react to
with combination of B. lactis Bi-07 and The molecular mechanisms on how treatment. Moreover, histological
L. acidophilus NCFM (Benor et al, 2014). gut microbes modulate adipogenesis examination showed clear
The objective was to evaluate if remain unidentified. Obesity is improvement of morphology and
maternal probiotic intake decreases characterised by dysregulated integrity. These preliminary findings on
the incidence of NEC, sepsis, and endocannabinoid system (eCB) tone B. lactis Bi-07 effects putatively have
death. Probiotic or placebo in the intestine and adipose tissue. In
value in several acute and long-term
supplementation started from 1 to 3 lean mice, activation of cannabinoid inflammatory conditions associated
days postpartum and was continued receptors leads to increased with bacterial translocation (Wei et al,
until the infant was discharged home. adipogenesis. Overactivation of the 2014).
Infants were breastfed and received at eCB system by cannabinoid receptor
least 50% of their enteral nutrition agonist leads to the leakage of the General health
from breast milk. The incidence of NEC intestinal barrier and in increase of Childs and colleagues analyzed in a
decreased by 66% and the incidence plasma LPS level in obese mice. In double-blind, randomized, cross-over
of Bell stage II NEC by 84% in those contrast, cannabinoid receptor study the effects of prebiotic (XOS,
infants whose mothers received antagonist improves gut barrier 8 g daily), probiotic (B. lactis Bi-07, 109
probiotics supplementation compared function (Muccioli et al, 2010). CFU daily) and synbiotic (XOS and B.
with infants whose mothers received lactis Bi-07) supplementation on gut
In a recent study, B. lactis Bi-07
placebo. Although the reduction of and immune function, blood lipids,
together with L. acidophilus NCFM
NEC incidence was non-significant, it and mood (Childs et al, 2014). Both
were administered to obese mice to
may be clinically relevant (Benor et al, treatments with XOS elevated fecal
evaluate the effect of probiotic
2014). There was no statistical bifidobacterial counts whereas the
treatment on gut permeability and
difference in the incidence of sepsis or probiotic supplementation only
activation of the eCB (Muccioli et al,
death between groups. elevated B. lactis. The microbiome
2010). Treatment with combination of was not observed to be affected
Oxalate-degrading activity B. lactis Bi-07+L. acidophilus NCFM otherwise although all three
In humans, accumulation of oxalic reduced eCB system tone, gut treatments had distinct effects on
acid can result in a number of permeability, and inflammation in short-chain fatty acids (SCFAs). XOS
pathological conditions, including obese mice. In addition, probiotic supplementation elevated plasma
hyperoxaluria, kidney stones, renal ingestion reduced fat mass HDL, which was linked to a trend of
failure, cardiomyopathy, and cardiac development in obese mice. The lower cholesterol levels, and vitality
conductance disorders. Intestinal results suggest a mechanism that and happiness. The other
oxalate-degrading bacteria could links gut microbiota to the regulation supplementations did not affect blood
prevent hyperabsorption of oxalate of adipogenesis and that probiotics lipids or self-reported moods.
and thereby participate in the may have beneficial effects in
maintenance of oxalate homeostasis. modulation of adipogenesis.
B. lactis Bi-07 has been shown to Uremia
perform high oxalate-degrading Uremic rats presenting inflammation
activity with 100% oxalate and elevated intestinal bacterial
degradation. The putative genes translocation were subjected to daily
induced during oxalate degradation in

14
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