Presentazione a cura del Professor Enrico Corazziari - M.A.S.T.E.R. ECM in Gastroenterologia: Focus on: Microbiota e dintorni - Fondazione Santa Lucia - Roma

1. STATO DELL’ARTE NELLO STUDIO
DEL MICROBIOTA
ENRICO STEFANO CORAZZIARI
Senior Consultant
Dipartimento di Gastroenterologia
ISTITUTO CLINICO HUMANITAS,
ROZZANO MILANO
enrico.corazziari@humanitas.it
GIÀ PROFESSORE ORDINARIO
Gastroenterologia
UNIVERSITÀ “SAPIENZA” DI ROMA
enrico.corazziari@uniroma1.it

2. IL NUOVO MONDO
TUTTO DA SCOPRIRE

5. Exploring flavour-producing core microbiota in multispecies solidstate fermentation
of traditional Chinese vinegar
Zong-Min Wang1,*, Zhen-Ming Lu1,2,*, Jin-Song Shi1,3 & Zheng-Hong Xu1,2,3
Scientific Reports | 6:26818 | DOI:
10.1038/srep26818

6. Ursell LK et al. Gastroenterology 2014;146:1470-1476
EXPLORING THE METABOLOMICS MICROBIOTA
INTERACTIONS

7. Exploring flavour-producing core microbiota in multispecies solidstate
fermentation of traditional Chinese vinegar
Zong-Min Wang1,*, Zhen-Ming Lu1,2,*, Jin-Song Shi1,3 & Zheng-Hong
Xu1,2,3
Scientific Reports | 6:26818 | DOI:
10.1038/srep26818

8. Exploring flavour-producing core microbiota in multispecies solidstate
fermentation of traditional Chinese vinegar
Zong-Min Wang1,*, Zhen-Ming Lu1,2,*, Jin-Song Shi1,3 & Zheng-Hong
Xu1,2,3 Scientific Reports | 6:26818 | DOI:
10.1038/srep26818

9. COMPLESSITA’
• Di raccolta
• Di conservazione del campione
• Di processazione del campione
• Di analisi del campione
• Di confrontabilità fra analisi
• Di analisi dei dati
• Di presentazione dei dati

10. INTERRELAZIONE TRA MICROBIOTA E
FUNZIONE INTESTINALE

11. GERM FREE MICE
 Longer Migrating Motor Complex
Intervals
 Enlarged Cecum
 Delayed Gastric Emptying
 Delayed Colonic transit
THESE EFFECTS ARE REVERSED AFTER MICROBIOTA ADMISTRATION
Abrams 1977;Caenepeel et al 1989

12. EFFECT ON TRANSIT, MICROBIOTA AND SCFA IN
GF.MICE COLONIZED WITH FECES OF
LOPERAMIDE-INDUCED CONSTIPATION

13. EFFECT ON TRANSIT, MICROBIOTA AND SCFA IN
IN GF.MICE COLONIZED WITH FECES OF IBS-C
PATIENTS

14. RECIPROCAL INTESTINAL MOTILITY-MICROBIOTA
RELATIONSHIP MAINTAINS AND REINFORCES
CONSTIPATION
SLOW
INTESTINAL
TRANSIT
MICROBIOTA

15. INTERRELAZIONE TRA MICROBIOTA E
DIETA
• Per variazioni dietetiche
• In funzione dei componenti della dieta

16. FOOD METABOLITES WITH EFFECTS ON
INTESTINAL MOTILITY AND
GUT-BRAIN AXIS
MICROBIOTA
• AMINOACIDS
METABOLYZING ENZYMES
• CHO
FERMENTATION
• BILE SALTS
DECONJUGATION
Serotonine
Histamine
Melatonine
Acetylcholine
NO
GABA
SCFA
H2
CH4
TGRS receptors

18. OPERATIONAL TAXONOMICAL UNITS (OTU) INCREASE
WITH LOW-FODMAP DIET
Schippa, Corazziari, Nicosia Personal Data
BEFORE AFTER

19. DIETA LOW-FODMAP: VARIAZIONI INDOTTE SUL
MICROBIOTA E SUI SINTOMI DEI PAZIENTI AFFETTI DA IBS
• STATISTICALLY
SIGNIFICANT
INCREASE OF
THE MEAN
RELATIVE
ABUNDANCE OF
F. prausnitzii
27/03/2017Schippa, Corazziari, Nicosia Personal Data
BEFORE AFTER
RELATIVE ABUNDANCE F. prausnitzii
BEFORE AND AFTER LOW-FODMAP DIET

20. INTESTINAL DISTENSION AFTER
GLUCOSE and FRUCTOSE INGESTION
A Khalaf et al. World J Gastroenterol Phathophysiol 2015;6:140-149

21. Differential Effects of FODMAPs (Fermentable Oligo-, Di-, Mono-Saccharides and Polyols) on
Small and Large Intestinal Contents in Healthy Subjects Shown by MRI
Kathryn Murray, Victoria Wilkinson-Smith, Caroline Hoad, Carolyn Costigan, Eleanor Cox,
Ching Lam, Luca Marciani, Penny Gowland and Robin C Spiller

22. FOOD AND ANTIBIOTIC MICROBIOTA INDUCED VARIATIONS
MODIFY INTESTINAL FUNCTION
INTESTINAL
FUNCTION
MICROBIOTA
FOOD ANTIBIOTICS

24. THE RECIPROCAL INTERACTION BETWEEN
MICROBIOTA AND NEUROENDOCRINE SYSTEM ON GI
FUNCTION

25. Nieuwdorp M et al. Gastroenterology 2014;146:1525-1533
THE EFFECT OF MICROBIOTA ON
METABOLISM

26. FECAL vs MUCOSAL MICROBIOTA in
CONSTIPATION
G Parthasarathy et al. Gastroenterology 2016;150:367-379

27. QUALITA’ CEPPO
Famiglia
Genere
Specie
Ceppo
Lactobacillaceae
Lactobacillus
rhamnosus acidophilus paracasei
XY LPC-S01
CNCMI1572
(L. casei DG®)
È il tipo di ceppo che determina la qualità del probiotico

28. LIMITS OF PROBIOTIC STUDIES
LITTLE NUMBER OF PROPERLY-PERFORMED
STUDIES
META-ANALYSIS POOL STUDIES WITH
 Different Probiotics
 Different Conditions
 Different Patients
 Few Patients
Direct-to-consumer marketing and lack of regulation
are obstacles to proper clinical studies
33
VERNA E.C. ET AL. THER ADV GASTROENTEROL 2010;5:307-319

29. Shanahan F et al. Gastroenterology 2014;146:1554-1563
SCIENCE AND CONSUMER VICIOUS CYCLE

30. FIGURE 2
Ability of LGG supernatants collected
corresponding to the middle exponential
(1), late exponential (2), stationary (3), and
overnight (4) phases to restore LPS effects
on cell shortening (black circle, dotted line),
inhibition of contraction (black triangles,
black line), and IL-6 production (black
triangles, dotted line). Data are expressed
as mean±SE of 5 experiments. LGG
indicatesLactobacillus rhamnosus GG.
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. 36
Protective Role of Postbiotic Mediators Secreted by
Lactobacillus rhamnosus GG Versus Lipopolysaccharide-
induced Damage in Human Colonic Smooth Muscle Cells
Cicenia, Alessia; Santangelo, Floriana; Gambardella,
Lucrezia; Pallotta, Lucia; Iebba, Valerio; Scirocco,
Annunziata; Marignani, Massimo; Tellan, Guglielmo;
Carabotti, Marilia; Corazziari, Enrico Stefano; Schippa,
Serena; Severi, Carola
Journal of Clinical Gastroenterology50:S140-S144,
November/December 2016.
doi: 10.1097/MCG.0000000000000681
LGG postbiotic effect

31. EFFECTS OF MICROBIOTA ON DRUGS

32. Petrof EO et al. Gastroenterology 2014;146:1573-1582

33. %0
10 %
20 %
30 %
40 %
50 %
%60
%70
80 %
90 %
%100
D3 R3t0 R3t1 R3t0 II R3t1 II
PAZIENTE R3
Firmicutes Bacteroidetes Proteobacteria
Fusobacteria Deferribacteres Actinobacteria
Cyanobacteria Synergistetes Chloroflexi

34. DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED CLINICAL TRIAL TO EVALUATE THE
EFFECTIVENESS OF FECAL MICROBIOTA TRANSPLANTATION TO RELIEVING SYMPTOMS IN
PATIENTS WITH IRRITABLE BOWEL SYNDROME UNRESPONSIVE TO STANDARD TREATMENTS.
Primary Endpoints (FDA-EMA) after 6 weeks:
 IBS-D responder: Decrease in weekly average of worst abdominal pain in the past 24 hours score of at
least 30% compared with baseline and decrease at least 50% in the number of days per week with at least
one stool that has a consistency of Type 6 or 7 compared with baseline
 IBS-C responder: Decrease in weekly average of worst abdominal pain in the past 24 hours score of at
least 30% compared with baseline and increase of 1 or more CSBM per week compared with baseline
 IBS –M,IBS-U responder: Decrease in weekly average of worst abdominal pain in the past 24 hours score
of at least 30% compared with baseline and improvement of global symptoms
0Run-in (10 Days)
R
A
N
D
O
M
I
Z
A
T
I
O
N
Group A
FMT
Group B
Placebo
0
I°Infusion
3 w
2°Infusion
06 w
Endpoints
evaluation
024 w
Follow up
Our experience
PATIENT 1
IBS-D T0 T1
Abdominal pain 7 2
IBS-SSS >300 75-150
B M 26 12
Bloating 5 3
BSC 6 3
PATIENT 2
IBS-U T0 T1
Abdominal pain 8 1
IBS-SSS >300 75-150
B M 12 8
Bloating 9 4
BSC 3 4

35. DOVE SIAMO NEL NUOVO MONDO
Le certezze
• Germ free animal
• Trapianto di microbiota intestinale per RCD
L’esplorazione
• Scomporre la complessità
• Valore della numerosità, delle relazioni tra famiglie, di una singola specie o di un
solo ceppo
• Ricostituire la complessità dal microbiota:dalle sue interrelazioni ai suoi metaboliti
alla funzione
• Trapianto di microbiota intestinale per IBD,IBS , malattie extraintestinali
• I probiotici e i postbiotici
Terre incognite
• Dal topo umanizzato all’uomo
• Microbiota fecale luminale vs mucosale distrettuale
• Modificare il microbiota per migliorare lo stato di salute