THE EFFECTS OF PROBIOTICS ON FEEDING TOLERANCE_BOWEL HABITS AND

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THE EFFECTS OF PROBIOTICS ON FEEDING TOLERANCE_BOWEL HABITS AND Powered By Docstoc
					THE EFFECTS OF PROBIOTICS ON
FEEDING TOLERANCE,BOWEL
HABITS AND GASTROINTESTINAL
MOTILITY IN PRETERM NEWBORNS



 FLAVIA INDRIO, MD

 Department of Pediatrics
 University of Bari, Italy
      LECTURE OUTLINES

• Possible mechanisms for the effects of
  probiotics on intestinal motility.
• Structure controlling intestinal motility
• Study techniques
• Our study on preterm newborns
    ACTIVITIES OF PROBIOTICS
•   Human origin
•   Non pathogenic
•   Resistance
•   Stability at different pH
•   Adhesion to epithelial receptors
•   Resistance in the intestine
•   Production of antimicrobial substances
•   IMMUNE MODULATION
•   METABOLIC EFFECTS
     BACKGROUND

Why the probiotic should have effect
on intestinal motility ?
 HOW DO BACTERIA
COULD INTERACT WITH
 THE MECHANISM OF
     MOTILITY?
RELATIONSHIP BETWEEN MICROFLORA AND
                GALT
 Development of Intestinal
Angiogenesis With Microbes

           • Villi from (P14) versus
             (P28) conventionally
             raised mice.
           • Capillary networks are
             stained green (FITC).




                Stappenback, Hooper and Gordon, PNAS, 2002
Delayed Colonization: Development
  of Intestinal Angiogenesis With
              Microbes




      Stappenback, Hooper and Gordon, PNAS, 2002
INTESTINAL PUMP
Mechanisms of interaction between the
  microflora and intestinal motility

 • RELEASE OF BACTERIAL
   METABOLITES (SCFA)
 • INTESTINAL NEUROENDOCRINE
   FACTORS
 • EFFECTS OF MEDIATORS
   RELEASED BY THE
   GASTROINTESTINAL IMMUNE
   SYSTEM
              SCFA
Bacterial metabolites (SCFA) have
metabolic effects on blood lipids and
carbohydrates and seem to stimulate
smooth muscle cellular calcium influx.
The role might be to co-regulate the
motility of the upper intestine.
IMMUNE MODULATION AND MOTILITY
         DISORDERS

   ENTERIC NERVOUS SYSTEM
   “neuroimmune interaction”
 Cellular mechanism
 Humoral mechanism
 Antineuronal Antibody
 Receptors
 (the well known entities are intestinal
   pseudobstructive disorders, IBS, post
   operative ileus)
IMMUNE MODULATION AND MOTILITY
         DISORDERS

 ENTERIC SMOOTH MUSCLE basically
 due to an inflammation of the GI
 mucosa rather than a inflammation of a
 muscle layer itself (mediated by TGF-
 beta and prostaglandin E2)
IMMUNE MODULATION AND MOTILITY
         DISORDERS

INTERSTITIAL CELLS OF CAJAL
  ganglioneuritis atrophy and vacuolar
  degeneration could be present
      METHODS OF STUDY
         MOTILITY
Modification of gastric electric
potential (EGG)

Movement of the intestinal         wall:
ultrasound and radiology

Modification    of    the     pressure:
manomety

Movement of the content: GI transit
       EGG PARAMETERS
mean frequency and dominant
frequency(DF)
instability coefficient
the percentage of DF defined as normal,
bradygastric and tachygastric
power ratio
                         Esempi di tracciati




                                        =Time x 64 s

Normale


          Bradigastria


                         Tachigastria
      ULTRASOUND
      PARAMETERS

Gastric emptying time
Gastric emptying rate
Fasting antral area
    PILOT STUDY DOUBLE BLIND
      PLACEBO-CONTROLLED

• L. reuteri for 30 days
• evaluation of the symptoms after the
  treatment
• Gastric emptying rate with ultrasound
  and EGG at time 0 and after 30 days of
  treatment
• Daily diary with all gastrointestinal
  symptoms and tolerance
            CLINICAL PARAMETERS

•   regurgitation
•   vomiting
•   “stool frequency”
•   weight gain
•   anthropometric data
•   air colic (daily crying time)
                   Demographic characteristics of the newborns
 Breast feed infant (BF)           Formula feed infants +placebo    Formula feed infants +
 (n° 10)                           (FP) (n° 10)                     Lact.Reuteri (FR) (n° 10)




 Mean gestational age 34 ±         Mean gestational age 34 ± 1.06   Mean gestational age 34 ± 1.13
 1.26

 Birth weight (g) 1920 ± 491.2     Birth weight (g) 1850 ± 342.2    Birth weight (g) 1890 ± 432.1


 Apgar score 8.76 ± 0.78           Apgar score 8.82 ± 0.78          Apgar score 8.92 ± 0.29


 Male/Female 8/2                   Male/Female 7/13                 Male/Female 14/6


 Vaginal/cesarian delivery 3/7     Vaginal/cesarian delivery 4/6    Vaginal/cesarian delivery 5/5



Values are given as mean and SD.
P=NS
                                    Mean of daily weight gain

                               45


                               40

                               35


                               30
       Weigth gain/day ( gr)




                               25


                               20


                               15


                               10


                                5


                                0
                                    Breast feed infant (BF)   Formula feed infants +placebo (FP)     Formula feed infants
                                                                                                   Lactobacillus Reuterii (FR)




p=NS
                                Number of feeds /day

                     7


                     6


                     5
Number of feed/day




                     4


                     3


                     2


                     1

                                 N.A.
                     0
                         Breast feed infant (BF)   Formula feed infants     Formula feed infants
                                                      +placebo (FP)       Lactobacillus Reuterii (FR)
                   Mean daily episodes of
                   regurgitation

                   6



                   5



                   4
   REGURGITATION




                   3



                   2



                   1



                   0
                       Breast feed infant (BF)   Formula feed infants     Formula feed infants
                                                    +placebo (FP)       Lactobacillus Reuterii (FR)




P<0.01
           Mean daily number of evacuation
                              6



                              5
         NUMBER EVACUATIONS




                              4



                              3



                              2



                              1



                              0
                                  Breast feed infant (BF)   Formula feed infants     Formula feed infants
                                                               +placebo (FP)       Lactobacillus Reuterii (FR)


P<0.01
                                   Mean of daily crying time

                        120



                        100
Crying time (min/day)




                         80



                         60



                         40



                         20



                          0
                                 Breast feed infant (BF)   Formula feed infants     Formula feed infants
                                                              +placebo (FP)       Lactobacillus Reuterii (FR)



                        P<0.01
           Mean daily episodes of vomiting

                3



               2,5



                2
    VOMITING




               1,5



                1



               0,5



                0

                     Breast feed infant (BF)   Formula feed infants     Formula feed infants
                                                  +placebo (FP)       Lactobacillus Reuterii (FR)



p<0.01
EGG values in preterm newborns fed formula with placebo , formula with Lactobacillus reuteri,
and breast feeding after 30 days of administration


                          Breast fed infant (BF)   Formula     fed   infants   Formula       fed       infants
                                                   +placebo (FP)               Lactobacillus reuteri (FR)


Preprandial EGG
Dominant frequency        2.9[2,7-2,9]             3.0[2.5-3.2]                3.1[2.6-5.8]
Instability coefficient   41.2[34-47]              35[34-54]                   43.8[39-50]
% Bradygastria            25.8[22-36]              22.5[11-22]                 29.0[19-32]

% normal slow waves       57.1[47-70]              64.5[40-74]                 54.8[51-61]
% Tachygastria            9.6[5.9-15.6]            12.9[3.2-32]                14.5[6.4-16.1]
Postprandial EGG
Dominant frequency        2.9[2.5-3.2]             2.9[2.7-3.1]                3[2.7-3.3]
Instability coefficient   35.5[33.9-43.2]          51.1[20.9-81.3]             39.3[35.1-45.2]
% Bradygastria            24[12-38]                26.2[12.5-49]               20.9[16.1-32.2]
% normal slow waves       64[47.5-77.2]            66.1[44.7-87.5]             67.7[54.8-70.9]
% Tachygastria            12.9[5.8-15.7]           6.4[0-12.9]                 12.9[9.6-16.1]
Power ratio               1.5[0.9-1.7]             1.3[1.3-1.3]                1[0.6-1.8]
Fasting antral area recorded from the three groups
of newborns after 30 days of intervention diet.




                                1 .7 5
    Fasting antral area (cm )
   2




                                1 .5 0
                                1 .2 5
                                1 .0 0
                                0 .7 5
                                0 .5 0
                                0 .2 5
                                0 .0 0




                                                                                 o
                                                 LR




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                                                          tm




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                                         Fo




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                                                                       ul
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                                                                  Fo
             Gastric emptying rates recorded from the three groups of

                       newborns after 30 days of intervention diet.

            100


             75
% GE rate




             50


             25


              0
                          LR




                                             i lk




                                                                      o
                                                                  eb
                                            m
                         a+




                                                                 ac
                                             t
                       ul




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                                                             pl
                   rm




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                                                            a+
                  Fo




                                      B




                                                        ul
                                                       mr
                                                     Fo
      Fo                        Fasting antral area (cm2)




                            0.00
                                   0.25
                                           0.50
                                                  0.75
                                                         1.00
                                                                1.25
                                                                       1.50
                                                                                    1.75
           rm
                ul
                  a+
                       LR
     B
       re
         as
            tm
Fo            ilk
  rm
    ul
      a+
                                                                                                                   Fasting antral area




         pl
           ac
             eb
                o




                                            % GE rate
     Fo                     0
                                      25
                                                  50
                                                                75
                                                                              100




        rm
          ul
            a+
              LR
      B
       re
         as
                tm
Fo                 ilk
   rm
     ul
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            pl
               ac
                 eb
                                                                                           Gastric emptying rate




                    o
          CONCLUSIONS

Clinical effects

• reduction of the daily number of
  regurgitation
• reduction of the daily crying time (air
 colic)
• increased number of evacuations
           CONCLUSIONS

    EFFECTS ON MOTILITY

•   faster gastric emptying rate
•   smaller fasting antral area
•   reduction of gastric residual
•   improved colonic motility
       CONCLUSIONS

No side effects
Safety and tolerance in preterm
The Effects of Probiotics on Feeding Tolerance, Bowel
Habits, and Gastrointestinal Motility in Preterm
Newborns
FLAVIA INDRIO, MD, GIUSEPPE RIEZZO, MD, FRANCESCO RAIMONDI, MD,
MASSIMO BISCEGLIA, MD, LUCIANO CAVALLO, PROF, AND RUGGIERO
FRANCAVILLA, MD, PHD
Probiotic supplements for preterm infants

There are now a number of trials demonstrating that live bacteria, similar to
those found in human milk (probiotics), may decrease the incidence of
necrotizing enterocolitis when fed to very preterm infants. There are no studies
of the physiologic effects of these organisms on gut function. In this issue of
The Journal, Indrio et al report their measurements of clinical symptoms and
gastric electrical activity and emptying in infants at about 34 weeks gestation.
These results suggest physiologic differences in GI function with lactobacillus
supplementation. Ultimately, any routine clinical use must await information
about which probiotic organisms should be given, at which dose, and for how
long.
–Alan H. Jobe, MD, PhD
                   Summary
• Intestinal microbes have major roles in various
  aspects of intestinal development and motor
  function during infancy.
• Manipulation of the microbes may have unforeseen
  long term effects that may be beneficial.
• In the the probiotics could act as a surrogate to
  promote the intestinal colonization
• We still have a lot to learn about intestinal microbes
  and their interactions with the developing host to
  manipulate them safely, especially in select groups,
  e.g. premature infants .

				
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