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COVID-19 and Clostridioides difficile Infections –
Can Synbiotics be a therapeutic option?
IX. POLISH/GERMAN SCIENTIFIC SYMPOSIUM, KOLBERG, POLAND
August 23-24.08.2021
by Prof. Dr. Henning Sommermeyer & Prof. Dr. Jacek Piatek
Department of Health Sciences
Calisia University
Kalisz, Poland
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer 1
Prof. Dr. Henning Sommermeyer
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer 2
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
3IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
4IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
5
A Short History of Probiotic Research
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
•History of probiotics is as old as the human history, as it is closely related to the use of fermented
food which probably started around 10,000 years ago.
•Modern history of probiotics starts with the work of the Russian scientist E. Metchnikoff, at the
beginning of 1900s
•investigating the positive effects of bacteria on human health
•proposing the possible to replace harmful microbes by useful microbes in the human gut
• Probiotic means “for life”, introduced by W. Kollath in 1953 to designate “active substances that
are essential for a healthy development of life.”
•In 1992, R. Fuller defined probiotics as “a live microbial food supplement which beneficially affects
the host by improving its intestinal microbial balance.”
•In 2013, an expert consensus document had been published on the scope and appropriate use
of the term probiotic: “live microorganisms which when administered in adequate amounts confer a
health benefit on the host”.
6
Probiotics
Probiotics Probiotic
microorganisms Bacterial probiotics
•Lactobacilli
•Bifidobacteria
Yeast probiotics
•Saccharomyces boulardii
Active Ingredient(s) Examples
Product Category
Definition
“live microorganisms which
when administered in adequate amounts
confer a health benefit on the host”
Source: World Health Organization
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Prebiotics
molecules that can be
used as source of
energy for
microorganisms
•Fructooligosaccharides
•Galactooligosaccharides
•Inulin
Active Ingredient(s) Examples
Product Category
7
Prebiotics
Definition
“a non-digestible food ingredient
that promotes the growth of beneficial microorganisms
in the intestines.”
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
8
Synbiotics
Definition
“a product containing
one or several probiotic microorganisms
combined with a prebiotic component”
Synbiotics
Probiotic •Probiotic bacteria
•e.g. Lactobacilli
•e.g., Bifidobacteria
•Fructooligosaccarides
Active Ingredient(s) Examples
Product Category
Prebiotic
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
No prebiotic component With prebiotic component
Probiotics
(beneficial microorganisms)
Yeast Probiotics Bacterial
Probiotics
Mono-strain
Probiotics
Multi-strain
Probiotics
Bacterial
Synbiotics
Mono-strain
Synbiotics
Multi-strain
Synbiotics
Categories of Products Containing Probiotic Microorganisms
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer 9
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
10IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
11
Mechanisms Used by Probiotics Against Pathogens
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Our Checklist for
Assessment of Products Containing Probiotic Microorganisms
Product Feature
Recommended
property
Reason(s)
Number of different
probiotics bacterial strains
5-10
Larger number of different probiotic strains contribute a variety of mechanisms to
contain pathogen growth in the gut, some of which might even act synergistically
Sufficient number of colony
forming units (CFU)
≥1 x 109
Sufficient
amount of CFU is needed to result in gut colonization. However,
colonization depends also on product features and probiotic strain characteristics
Protection against
inactivation by stomach acid
enteric coating
Enteric coating of capsules or powders will allow living bacteria to travel through
low pH environment of the stomach
Symbiotic
probiotic combined
with prebiotic
The prebiotic component will provide a source of energy for the probiotic strains,
thereby supporting the colonization of the gut by the probiotic bacteria
Allergens
free of allergens
Product should be free of allergens, especially, lactose
-free and gluten-free
Capsule
vegetarian capsule
Gelatin
-
free and are acceptable for users, who have to avoid products containing
components sourced from pigs
Packaging
blister or stick pack
Blister packaging or one
-dose stick packs provide convenient administration
Dosing
once daily
Once
-daily dosing is supporting compliance of intake
Storage
room temperature
Storage without refrigeration simplifies logistics and storage by users
Acceptable price
acceptable
Must be low enough to allow out
-of-pocket payment by patients
12
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
13IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Clostridioides difficile (formerly Clostridium difficile)
14
•Gram-positive, spore-forming, rod-shaped
•Anaerobic
•Optimum growth on blood agar at temperature
around 37°
•Major toxins are enterotoxin A and cytotoxin B
which distrupt cytoskeleton signal transduction
in host cells
•Transmission mainly by fecal-oral route
•Symptoms of C. difficile infection range from
diarrhea to potentially lethal pseudomembra-
nous colitis (PMC)
•Drug-resistant isolates are important hospital-
acquired bacterial pathogens
Scientific Classification
Domain: Bacteria
Phylum: Firmicutes
Class: Clostridia
Order: Clostridiales
Family: Peptostreptococcaceae
Genus: Clostridioides
Species:C. difficile
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Emergence and Spread of Resistance in C. difficile
1980-90s 2000s 2020
Cephalosporines Quinolones First strains
resistant against
Vancomyin
&
Metronidazole
1970
Clindamycin
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer 15
OO
HO
R1
R3
R2
R4
N
F
O
O
O
ON
NS
H
H
R1
R2
H
O
O
OH
OH
OH
Cl
N
N
S
H
H
Antibiotic Resistance Profiles of tested C. difficile Strains
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer 16
Antibiotic
C. difficile
ATCC®9689™
PCR-ribotype 001
C. difficile
No. 977
PCR-ribotype 001
C. difficile
No. 644
PCR-ribotype 027
Clindamycin
aS R R
Erythromycin
bS R R
Ciprofloxacin
bR R R
Moxifloxacin
cR R R
Imipenem
bMS R R
Metronidazole
aS S S
Vancomycin
aS S S
R: resistant (MIC-values ≥ resistance breakpoint concentration), S: susceptible (MIC-values ≤ resistance breakpoint concentration), MS: medium susceptible ((MIC-
values equal to resistance breakpoint concentration) . aResistance breakpoint taken from EUCAST, bresistance breakpoint taken from CLSI, cepidemiological cut-off
concentration taken from EUCAST.
Pathogenicity Locus of C. difficile
17IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Mutation in Hypervirulent PCR-Ribotype 027 C. difficile Strains
18IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
19IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
In-vitro Pathogen Growth Inhibition
A Sac. boulardii
B L. rhamnosus GG
C Multi-strain synbiotic A
(Vivatlac Synbiotic)
D Multi-strain synbiotic B
(Vivatlac Baby)
A
B
D
Escherichia coli EPEC
C. difficile
37°C
24 hours
20
C
absence of O2
0,0 5,0 10,0 15,0 20,0
Sac. boulardii
L. rhamnosus GG
Multi-strain synbiotic A
Multi-strain synbiotic B
Inhibition [cm]
C. difficile No 644 PCR-ribotype 027 C. difficile No 977 PCR-ribotype 001
C. difficile ATCC 9689 PCR-ribotype 001
Results of In-vitro Pathogen Growth Inhibition Experiments
21IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Our publication is availalbe as open access
https://www.mdpi.com/1660-4601/18/11/5871
VIII. Scientific Symposium Kolberg,PL, 2020/Sommermeyer 22
What Topics Will Be Covered In This Session?
Our Learnings
In-vitro inhibition of multi-drug resistant C. difficile strains
C. Difficile strains: Resitance profiles and PCR ribotypes
Potential anti-pathogen mechanisms of probiotics
Products containing probiotic microorganisms
23IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Synbiotics and C. difficile
Resistances against a broad range of antibiotics, lately
also against metronidazole and vancomycin, is widley
spreading in C. difficile strains, making C. difficile
infections (CDI) a worldwide challenge for healthcare
11
Growth of C. difficile strains can be inhibited by multi-
strain synbiotics independent of their antibiotic
resistance and PCR-ribotype profiles
22
Multi-strain synbiotics should be considered as
prophylactic or complimentary therapy when
antibiotics are prescribed, especially in patients at risk
for CDI (e.g., elderly, recurrent CDI)
33
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IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
For Those of You Interested in C. difficile
Available early October 2021
25IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer
Clostridioides difficile
Infections, Risk Factors, Prevention and
Treatment
Authors: Sommermeyer, Henning, Piątek, Jacek
•Offers a comprehensive and up to date overview
on Clostridioides difficile and C. difficile
infections
•Covers all relevant scientific aspects, from
microbiology, and pathophysiology, to risk
factors, and prophylaxis
•Enriched with accurate illustrations that support
the reading experience
Questions, Comments & Suggestions
26
E-mail: h.sommermeyer@akademiakaliska.edu.pl
IX. Scientific Symposium Kolberg,PL, 2021/Sommermeyer