Lactobacillus reuteri is a probiotic strain that provides several benefits for infant health and digestion. It reduces crying time in colicky infants by modulating the gut microbiota and decreasing levels of gas-forming bacteria like E.coli. It also reduces inflammation in the gut by immunomodulation, promoting the development of regulatory T cells. Furthermore, L. reuteri promotes development of the enteric nervous system, improving gut motility and decreasing visceral pain. Clinical studies show L. reuteri is more effective at reducing infant crying time compared to the antacid simethicone.

1. Role of Lactobacillus. Comfortis
(L reuteri)
in
Colic & Easy digestion -
Comfortable and Healthy Baby
Dr Kuntal Biswas
MBBS, DPH, DNB(P), FCCP, FCAM, FMCESA
Medical Registrar
Medical College & Hospitals, Kolkata.

2. What is Crying?
• Crying is a normal reflex every newborn has , and
one of the neonatal reflex babies are born with. It
is a brilliant way of getting attention and it is a
powerful connection between the baby and the
mother.
• It is estimated to be 80 - 100 db sound of
prolonged period (most adult can’t do)
• 50% of infant age 6 week cry almost 2h/day and
at 12 weeks this cry decrease to 1h/day
• Crying of early infancy is an excellent signal of
need. But poor signal of what is needed.
2

3. Functional gastrointestinal disorders
• More than half of all infants experience mild functional
gastrointestinal symptoms.
Functional gastrointestinal disorders, i.e. those not caused by organic
illness, are very common in infants during the first months of life.
This stems from the fact that the gastrointestinal tract must first “get
used” to its new functions after birth.
• The clinical symptoms of functional gastrointestinal
disorders include colic, spitting up, flatulence, constipation
and mild diarrhoea.
• Some probiotics bacteria have the potentiality to provide
“gut comfort”, but not all probiotics bacteria are equal.
• L. reuteri DSM 17938 - a strain that provide “gut comfort”
3

4. Symptoms + signs that suggest a
diagnosis other than colic
•Failure to thrive
•Irritability that is almost continuous, rather than episodic
•Irritability that lasts beyond 3 or 4 months
•Vomiting, Diarrhea, constipation
•Heme positive stool
•Rash
•Respiratory symptom
•Point tenderness in an extremity
•Anal fissures
•Subtle dysmorphic facial features
4

5. Definition of Colic
• Paroxysm of irritability, fussing
or crying lasting more than 3
hours/day
• For more than 3 days/week
after other causes for crying .
• resolve by 3 month of age.
• Colic starts at two weeks of age
and last till 3 month
• In premature babies it starts
two weeks after the due date.
• Incidence: 2 % to 12 %
5

6. Causes of Colic
•There is an association between low birth
weight and increased incidence of colic.
• It is equally likely to occur in both breastfed
and formula-fed infants due to aerophagia.
• Increased levels of certain biochemical markers,
such as motilin, alpha lactalbumin, and
urinary 5-hydroxy-3-indole acetic acid (5-OH HIAA).
• Psychosocial stress during and after pregnancy is
associated with colicky babies.
• Colic affects 10-30% of infants worldwide.
• Some evidence that there is an increased allergic disorders
and certain psychological disorders.

7. Classic Treatment
1.Recommend that the smell of the mother is familiar to the baby.
2.Dicyclomine hydrochloride is an anticholinergic drug that is
effective in the treatment of colic.
Because of serious, although rare, adverse effects (e.g., apnea, breathing
difficulty, seizures, syncope), its use cannot be recommended.
3.Train parents about the importance of sign of hunger of the baby, changing
wet diapers, and comforting a baby who is cold and crying as a result of
kinking of respiratory tube.
Soothing music accompanied with parental attention (including eye contact,
talking, touching, walking, and playing) may be effective in some infants.
4.Encourage parents to discuss their feelings and concerns with each other to
obtain support.
Emphasize the responsibility of the whole family in the care of a colicky baby.

8. Causes of Infantile Colic
Past investigations included:
• Inadequate or inappropriate
mother-infant interaction
• Mother’s anxiety
• Abnormal Gastrointestinal
Function
• Transient Relative Lactase
Deficiency
• Exposure to Cow’s Milk
Proteins
8

9. What are probiotics?
• The WHO definition of Probiotics bacteria “life micro
organisms, which when consumed in adequate
amounts, confer a health effect on the host“
(WHO/FAO).
• Probiotics includes a whole range of completely
different micro organisms endowed with different
properties and effects.
• Some of the mechanisms behind the beneficial effects
are valid for all of the genera and strain lactobacilli and
bifidobacteria.
• Many properties and effects are strain-specific.
Every strain and every combination of different strains must
be tested separately in clinical studies for its beneficial
effects on the host. 9

10. Probiotics
• Induction of dendritic cell (DC) maturation.
• Enhancement of serum antibody response to orally and
systemically administered antigens.
• Enhanced immuno -reactivity of spleenic cells and
phagocytes.
• Activation of the gene for human beta defence in
intestinal mucosa Induction of oral tolerance to
beta lactoglobulin.
• Production of beta- galactosidase - improvement of
lactose intolerance
• Induction to reduce local inflammation in GIT
10

11. How can the same probiotic strain help with so
many different
functional gastrointestinal disorders?
The gastrointestinal tract is It also houses
the body’s
not just a digestive system;
largest immune
system,
gut-associated
lymphoid tissue
(GALT),
and the enteric
nervous
system (ENS).
11

12. Cont….
There is a 4th organ in the gut: the gut micro flora .
It influences the maturation and regulation of the functions
of all 3 organ systems through direct effects as the gut flora
is still subject to important changes at that age . 12

13. Lactobacillus reuteri
•It is an obligatory heterofermentative
resident in the gastrointestinal tracts of
humans.
•It produces compounds that exhibit
antagonistic activity, i.e. reuterin and
reutericyclin, which are water-soluble,
broad-spectrum antimicrobials,
effective over a wide pH range,
and resistant to
proteolytic and lipolytic enzymes.
13

14. What do we know about the effect
mechanisms of L. reuteri?
- Modulates gut flora
- Modulates the immune responses und inflammatory
responses in the gut mucosa
- Promotes postnatal intestinal neuronal development,
thereby furthering gut motility
- Inhibits visceral pain coming from the gastrointestinal
tract and decrease tonic contractions of the muscles of
the colon caused by pressure
- Normalizes disturbed sleep patterns
14

15. How does L.reuteri modulate
gut microbiota?
• It temporarily colonize the gut and
increases their number after ingestion.
• It ferment easily fermentable sugars to
produce energy.
• During this process they produce lactic
acid, which reduces the intra-luminal
pH value.
• The acid milieu inhibits the growth of
potentially pathogenic bacteria in the
Changes in the number of gut while promoting the growth of
E. coli & lactobacilli lactobacilli and bifidobacteria.
It compete with potential pathogens for nutrients and
the attachment sites for docking onto the gut mucosa 15

16. Cont…….
• It produces reuterin
(3-hydroxyproprionaldehyde),
an anti-microbial compound
• Reuterin is active against a wide
spectrum of gram-positive and
gram-negative bacteria (e.g.
E. coli), yeasts, fungi and viruses.
• It kills the pathogenic bacteria,
whereas it does not touch the
good bacteria.
• The direct contact of L. reuteri with
other bacteria, such as E. coli,
stimulate reuterin production or
secretion.
• Reuterin inhibits bacterial growth
by inducing oxidative stress in the
bacterial cell.
• L. reuteri itself is highly resistant to
the effects of reuterin 16

17. L. reuteri compared to other Probiotics:
effects on pathogens
17

18. Histamine Derived from Probiotic L. reuteri
suppresses TNF
• Histamine is produced from L-histidine via histidine
decarboxylase by some fermentative bacteria including
lactobacilli.
• Targeted mutagenesis of each gene present in the
histidine decarboxylase gene cluster in L. reuteri 6475
demonstrated the involvement of histidine decarboxylase
pyruvoyl type A (hdcA), histidine/histamine antiporter
(hdcP), and hdcB in production of the TNF-inhibitory factor.
18

19. For which clinical effects is the modulation of
the gut microflora through L.reuteri
especially important?
Clinical Findings and/or rationale Potential effect mechanisms
effects
L. Reuteri Colicky infants have a Fecal gas-forming E. coli were
reduces lower prevalence of significantly reduced during L. reuteri,
lactobacilli and higher but not during placebo
crying counts of fecal E. coli supplementation.
time than healthy infants
in The abundance of gas- Higher counts of E. coli in colicky
colicky forming E. coli may lead infants, suggests that reduction of
infants to excessive intestinal faecal gas-forming E. coli by
air load and consequent L. reuteri can help to reduce
abdominal pain crying time in colicky infants
19

20. Cont….
Clinical Findings Potential effect mechanisms
effects and/or rationale
L. reuteri There are L. Reuteri & lactobacilli,
improves indications that produce lactic acid and other
functional the intestinal acids.
constipation flora is
disturbed in This reduces the pH value in
children with colon.
chronic
constipation A lower pH enhances
peristalsis of the colon and
subsequently decreases
colonic transit time, which in
turn helps against constipation
20

21. Modulation of the immune responses und
inflammatory responses of the gut mucosa
• The gut-associated lymphoid tissue (GALT) is largest immune organ.
It includes more than 2/3 of the total lymphoid tissue of the human
organism and around 80% of all IgA producing plasma cells.
• Gut bacteria are the “coaches” of the gut immune system.
• One advantage of “good” probiotic vs. “bad”, i.e. potentially pathogenic
bacteria is that they “train”. 21
As a result, the immune system maturates without risk of disease.

22. What do we know about the beneficial
immunomodulatory effects of L. reuteri?
The role of T helper cells
The major players in the specific, “acquired” or adaptive immune system are
T cells and B-cells.
T-helper (Th) cells are a subset of T-cells. Th cells are also called CD4 positive
(CD4+) T cells, as they have the surface protein CD4. Th cells play a central role
in immune protection, i.e. to secrete antibodies. .
They send an order to the B-cells which produce specific “weapons-chemical
messengers” cytokines (immunoregulatory proteins)” against foreign 22
substances.

23. A clinical study shows:
The ingestion of L. reuteri induces colonization of the
ileum & is associated with a significantly higher amount
of T-helper cells in the ileal mucosa
T-helper cells in ileal mucosa
A) before (“dispersed cells or aggregations of cells”);
B) after L. reuteri administration for 28 days
23

24. For which clinical effects immunomodulatory
effects of L. reuteri especially important?
Clinical effect Findings Potential effect mechanisms
L. Reuteri Calprotectin The increased
(marker of Gut calprotectin -
reduces levels in infants with
inflammation)
crying colic show that colic is
levels are associated with a low-
time
significantly grade gut
in infants higher (2-fold) inflammation.
The effect of L. reuteri of
in infants with
down-regulating
colic compared pro-inflammatory cytokine
with control IFN-γ in the intestine &
infants inhibiting gut inflammation
24

25. Promotes postnatal intestinal neuronal development & development &
regulation of a normal motility of the gastrointestinal tract
The digestive system has its own enteric nervous system (ENS).
The total number of enteral neurons in the human GI tract is about 100 million.
The principal components of the ENS are two networks or plexuses of neurons, both
of which are embedded in the wall of the digestive tract and extend from
oesophagus to anus:
1)The myenteric plexus, which exerts control primarily over digestive tract motility
2)The sub mucosal plexus of which the principal role is sensing the environment
within the lumen.
In the jejunum L. reuteri supplementation increased the contractile response to
acetylcholine whereas it had no effect in the colon .
The contractile response to EFS was significantly increased in both jejunum & colon
which suggests that L. reuteri promoted the development and function of the enteric
nervous system (ENS).
25

26. Inhibitory effects on visceral pain
Specialized “pain receptors”, nociceptors, are
located in the walls of the G.I tube.
They are particularly sensitive to stretch
and over-distension of the walls of the
gastrointestinal tract tube.
Once a certain degree of distension is reached,
the nocireceptors “feel” the pressure &
“respond” by translating the mechanic stimulus
into electrical signals and conducting the
signals into the spinal cord through afferent*
spinal nerves.
From the spinal cord, the nerve fibers transmit the electrical signals on to
the brain. When they reach the brain, we become aware of the pain.
Visceral pain is typically accompanied by a slowed heart rate
When strong mechanical stimuli such as extreme distension of the walls of
the gastrointestinal tract tube, the vagus nerve (vagal afferent) is also
stimulated. This can induce automatic responses to painful stimuli.
Typical automatic responses to painful stimuli include a slowed heart rate 26
and a reduction in blood pressure.

27. Results study of comparison of effectivity of
L.reuteri & Simethicone
• Primary Outcome
– Reduction of the daily average crying time,
from baseline to the end of the treatment
period, to <3 hours/day
• Secondary Outcome
– Number of responders vs. nonresponders in
each group at the end of treatment
• Responders = a decrease in the daily
average crying time of 50% during the
study. 27

28. Crying Time (min)
Day L. reuteri Simethicone Difference P-value
0 197 (180-276) 197 (180-278) 0 .987
1 192 (107-273) 192 (107-278) 0 .753
7 159 (54-211) 177 (38-241) -18 .005
14 95 (41-170) 153 (51-231) -58 <.001
21 74 (35-139) 154 (54-229) -80 <.001
28 51 (26-105) 145 (70-191) -94 <.001
28

29. Comparison of effectivity of
L.reuteri & Simethicone
100
90
80
70
60
50 Responders
Nonresponders
40
30
20
10
0
L. reuteri Simethicone
29

30. Normalization of disturbed sleep patterns
Sleep follows a regular cycle each night.
Sleep is divided into two main stages: rapid eye movement
(REM) and non-rapid REM (NREM) sleep.
REM sleep is characterized by muscle relaxation.
NREM sleep, time of quiet sleep, ranging from light to deep
phase.
In 8-hours of sleep, the human brain cycles through these
stages about 4-5 times.
An animal trial shows:
L. reuteri normalizes the 24-hour duration of wake & sleep
stages and sleep fragmentation 30

31. International Journal of
Food Microbiology 95 (2004) reports
• Lactobacillus reuteri in fermented bovine
milk decreases the oral carriage of mutants
streptococci.
• Bovine milk fermented by L. reuteri
decrease the risk of dental caries.
• This organism may be a useful probiotic
organism for dairy products.
31

32. Whey components linked to immune modulation
80%
• Immunoglobulins
CASEIN
β –lactoglobulin
• Lactoferrin
20%
Minor proteins α -Lactalbumin
• Alpha-lactalbumin
αS1- Casein Amylases Proteose Peptones
• Minor proteins Lipases
- Lactoperoxidase Blood Serum Albumin
γ- Casein Peroxidase
Catalases
- Lysozyme κ- Casein
Immunoglobulins
Lactoferrin
- Proteose peptones αS2- Casein
Phosphatases
β- Casein
WHEY
Confidential to Fonterra

33. Whey components linked to bone health
80%
• Glycomacropeptide
CASEIN
β –lactoglobulin
• Lactoferrin
20%
Minor proteins α -Lactalbumin
• Alpha-lactalbumin
αS1- Casein Amylases Proteose Peptones
• Minor proteins Lipases
• Fractions γ- Casein
Blood Serum Albumin
Peroxidase
Catalases
κ- Casein
Immunoglobulins
Lactoferrin
αS2- Casein
Phosphatases
β- Casein
WHEY
Confidential to Fonterra

34. Primary components of whey protein and
their benefits
Whey Component % of Benefits
Whey
Protein
Beta-Lactoglobulin 50-55% Excellent source of essential amino acids especially
branched-chain amino acids
Alpha-Lactalbumin 20-25% Excellent source of essential amino acids; High in
Tryptophan which helps regulate sleep, mood & stress
Immunoglobulins 10-15% IgA, IgD, IgE, IgG, IgM – primarily IgG with immune
enhancing benefits
Lactoferrin 1-2% Antioxidant, anti-viral, anti-bacterial, anti-fungal; promotes
beneficial bacteria; regulates iron absorption
Lactoperoxidase 0.5% Inhibits bacterial growth
Bovine Serum 5-10% Good profile of essential amino acids
Albumin
Glycomacropeptide 10-15% Inhibits formation of dental plaque and cavities
Source: Alternative Medicine Review (2008), Vol 13 (4), pp 341-347
Confidential to Fonterra

35. Approximate yield from milk (assuming no losses)
Casein
32 kg
Skim milk
889 kg Lactose
851 kg
Casein whey
857 kg
Cream
111 kg
Whey
whole milk 6 kg
1000 kg
(=1 tonne)

36. Summary
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37. Summary
37

38. Thanking
You All
38