PROBIOTIC

dr. Nafi’uddin Mahfudz,. SpPD. MKes. FINASIM

International Journal of Pharma and Bio Sciences Vol.1/Issue-3/Jul-Sep.2010 1

• Syrup Jagung tinggi fruktosa justru meningkatkan
resistensi insulin (DM) dan lemak perut
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Probiotics (Greek) arti : “for life,” untuk kehidupan.

FAO and WHO adl : mikroorganisme yang jika

diberikan dalam jumlah yg adekuat dapat
memberikan mafaat kesehatan bagi tubuh host /
inang.

Probiotic yang baik :

- non-pathogenic,
- nontoxic,
- resistant thd asam lambung,
- melekat epithelial usus
- menghasilkan antibacterial
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 KOMPOSISI PROBIOTICS
Probiotics biasanya bacteria ↑↑, jamur, ragi.

(Lactic acid bacteria, Streptococci and Bifidobacteria)

Lactobacillus acidophilus, L. casei, L. lactis, L. helviticus,

L. salivarius, L. plantrum, L. bulgaricus, L. rhamnosus,
L. johnsonii, L. reuteri, L. fermentum, L. del brueckii.

Streptococcus thermophilus, Enterococcus faecium,

E. faecalis,

Bifidobacterium bifidum, B. breve, B. longum and

Saccharomyces boulardii.

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Figure 5.7 A false color scanning Figure 5.8 A scanning electron
electron micrograph of the surface micrograph of bacteria (colored green)
of the colon mucosa with clusters of adhering to the surface of cells in the colon.
bacteria (possibly E. coli) attached.

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Figure 5.9 A colorized scanning
electron micrograph of cells of the
human bladder infected with bacteria.
Rod shaped E. coli (colored yellow) are
seen attached to the epithelial cells of the
bladder (colored blue). Note the purple
colored cells which have swelled and
developed a rough surface due to this
chronic bladder infection.
Figure 5.10 A colorized scanning electron
micrograph of dental plaque.
The yellow-green structures are Streptococcus
mutans adhering to a biofilm that covers the
teeth. Other organisms adhere to S. mutans
and cause the development of a biofilm. The
organisms in this biofilm produce the enzymes
that can cause destruction of the tooth,
resulting in the formation of a cavity.
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gut microbiota can affect a variety of host
responses

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FIGURE 3 | Proposed mechanisms of action.
Thereareavarietyof proposed mechanisms, including both humoral and neural routes, through
which the microbiota can modulate signaling along the brain–gut axis.
Forexample,recent studies suggest a role for both the vagus nerve and modulation of systemic
tryptophanl evels in relaying the influence of both resident andexogenous microflora along this
bidirectional communication axis. study which conclusively implicated the vagus nerve in the
direct
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The microbiota–gut–brain axis:
neurobehavioral correlates

Montiel-Castro et al October 2013| 21

John F. Cryan and Timothy G. Dinan
Nature Reviews Neuroscience | AOP, published online 12 September 2012 22
(brain-gut-microbiom communication in health and disease, Grenham et al. 2011) 23
 MECHANISMS OF ACTION
Mekanisme aksi probiotik :
- kompetisi reseptor,
- immunomodulasi ( gut-associated lymphoid tissue)
- menurunkan mediator proinflammasi.
- menghambat colonisasi kuman pathogen,
- produksi substansi antimicrobia,
- menghambat perlekatan kuman pathogen,
- degradasi toxins,
- stimulasi immunitas lokal and peripheral ,
- stimulasi aktivitas enzym brush border enzyme
- stimulasi sekresi-IgA

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MECHANISME OF ACTION ON INFECTION

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 PREBIOTIK
• Fructooligosaccharides, inulin, oligofructose, lactulose,
dan galactooligosaccharides dikenal sbg prebiotic.

• Mempunyai sifat tahan thd asam lambung,

• dpt difermentasi mikroflora gastrointestinal
• merangsang pertumbuhan dan aktivitas intestinal
bacteria yg bermanfaat.

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 CLINICAL APPLICATIONS
Anti-diarrheal Effects

Specific strains lactobacilli mengurangi diare akut yg

disebabkan rotavirus pd infant dan dewasa.
(Lactobacillus GG, L. casei, B. bifidum and S.
Thermophilus).

Mekanismenya :
- competitive blockage of receptor sehingga mencegah
invasi virus.
- meningkatkan immune response, membentuk IgA
melawan rotavirus.
- Lactobacilli memproduksi Glycosylated intestinal mucins
yg menghambat rotavirus.
- lactobacilli menghasilkan substansi yang menekan
aktivasi partikel virus. 28
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 Protection against Infections
L. rhamnosus GG, Bifidobacterium, L. acidophilus, and S.
Thermophilus →enekan aktivitas bacteri pathogen ISPA
(upper tract resp infection)

Lactobacillus casei strain Shirota, Bifidobacteria and

Lactobacillus salivarius menghambat kolonisasi H. Pylori.

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 Anticancer activity

Mekanisme lactobacilli sebagai anticancer :

1. menetralkan substansi procarcinogenic (e.g., nitrates);
2. menurunkan kadar carcinogen
3. menekan metabolic action bakteri
4. Menekan induksi dan pertumbuhan tumor scr langsung.

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 ANTICANCER EFFECTS

• Menghambat transformasi procarcinogen menjadi

carcinogen aktif.
• Mengikat bahan mutagenic.
• menghasilkan substansi antimutagenic.
• Menekan pertumbuhanbakteri pro-carcinogenic.
• Menghambat absorpsi bahan mutagens di intestine
• Meningkatkan fungsi immune thd cancer
L casei strain Shirota

Microbial Ecology in Health and Disease. 2009; 21: 1_27

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L. rhamnosus GG and bifidobacteria ,L. rhamnosus
GG and LC-705 and a Propionibacterium sp. →
menurunkan aktivitas carcinogenic aflatoxin dlm
lumen usus.

Meningkatkan aktivitas glutathione transferase

(induced by Bifidobacterium longum)

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Assisting Vitamin and Mineral Uptake
Probiotics increase the bioavailability of vitamins and protein in
the GI tract as a result of increased acidification of the gut pH
by the lactic acid produced by bacterial strains.

Compared to milk, yogurt results in better absorption of such

vitamins and minerals as calcium, copper, iron, manganese,
phosphorous and zinc.

Prebiotics also improve calcium bioavailability

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 Probiotic as anticholesterol

• assimilasi cholesterol oleh probiotics [28],

• co-precipitation of cholesterol with deconjugated bile [29],
• cholesterol binding to cell walls of probiotics [30],
• and production of short-chain fatty acids upon fermentation
by probiotics in the presence of prebiotics.
• Lactobacillus memproduksi niasin → menurunkan VLDL →
konversi VLDL mjd LDL ↓

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Figure 2. Scanning electron micrograph of Lactobacillus bulgaricus cultivated in
media without cholesterol and (B) broth supplemented with cholesterol (100 mM).
Int. J. Mol. Sci. 2010, 11, 2499-2522

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 Probiotic and allergie

- Menurunkan respon inflamasi (menurunkan CD4 serum and

eosinophilic protein X urin).
- induksi T regulator (Tr) cells dan counter-regulation oleh Th1 cells,
- menurunkan immunogenisitas allergen melalui modifikasi struktur.
- Memperkuat pertahanan mucosal (production of IgA),
- Stabilisasi ‘gut mucosal barrier’

Lactobacillus GG meningkatkan transforming growth factor-ß ,

induction of IL-10 production and regulation of phagocytic cell
function.

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Int. J. Mol. Sci. 2009, 10, 3755-3775;

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 The renin system plays a central role in
regulation of BP

Renin is released
into the vasculature

Juxtaglomerular cells

Glomerulus
 Renin Angiotensin
System (1)
Classical "circulating" system (RAS):

glomerular zone adrenal

Angiotensin II glands

ACE Aldosterone

Angiotensin I Na+-retention
K+-loss
Renin Renin
macula Blood pressure
Angiotensinogen densa
Na+
Sympathetic system
Adapt. from Dominiak & Unger (eds.) in Ang II-AT1-
Receptor Antagonists, Steinkopff (1997)
 Angiotensinogen

SISTEM RAA Renin

Angiotensin I
ACE

Angiotensin II

Aktivitas Vaso- Sekresi Sekresi Minum

Simpatis konstriksi Aldosteron ADH

Retensi Na
Kontraktilitas Resistensi Ekskresi K
miokard perifer
& Retensi H2O
Denyut
jantung Volume
Tekanan darah
darah Tekanan
(Bambang, 2009 pada seminar hipertensi) perfusi ginjal
ACE inhibitor peptide : didapat dr produk fermentasi
keju, fermented milk, soymilk and yogurt.

Dalam prosesnfermentasi, sejumlah probiotics

mampu menghasilkan ACE inhibitory peptides yg
diketahui sbg zat antihipertensi.

Lactobacillus helveticus dapat menghasilkan

antihypertensive peptides.
Bifidobacterium longum and Lactobacillus acidophilus
menunjukkan aktivitas sbg ACE-inhibitor.

Penelitian probiotik sbg antihipertensi spt berikut :

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 Probiotic and Diabetes

Int. J. Mol. Sci. 2009, 10, 3755-3775 47

 mechanisms inhibition of Gram negative
bacteria by probiotics :
• Kompetisi nutient dan tempat perlekatan bakteri patogen
• Produksi substansi antibakteri bacteriocins,
• Produksi asam lemak rantai pendek(short chain fatty acids)
berperan dlm menurunkan koloni bakteri pathogen.
• Diet high fructose dapat induce type II diabetes ( insulin
resistance, hyperinsulinemia, hypertriglyceridemia and
hypertension)
• akumulasi fructose dalam liver meningkatkan lipogenesis
dan synthesis triacylglycerol.

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• Alloxan adl analog toxic glucose yg merusak
sel β pancreas yg menyebabkan insulin-dependent
diabetes mellitus.

• Matsuzaki et al. : lyophilized Lactobacillus casei

dapat menghambat sintesis alloxan (bersifat
merusak pancreatic β-cells) menyebabkan diabet-
BALB/c mice.

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Mekanisme probiotic/ Lacto B menurunkan
asam urat

Ogawa 2012 52
 Mekanisme probiotik sbg anti
asam urat
• Diet tinggi purin dalam usus dimetabolisme
menjadi : purine nucleotide dan purin
nucleosidase → bersifat mudah diabsorpsi →
kadar plasma asam urat tinggi.

• Lacto B mengubah purine nucleotide dan

purin nucleosidase → purine base (sulit
diabsorpsi) dibuang mll feses

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 GUIDELINES FOR THE EVALUATION OF
PROBIOTICS

identify and characterize the organism to the genus and species level with
internationally accepted methods, such as DND-DNA hybridization and
sequencing of DNA encoding 16S rRNA (147).

For strain typing, pulsed-field gel electrophoresis is the gold standard, but
randomly amplified polymorphic DNA can also be used (43).

Determination of the presence of extrachromosomal genetic elements such

as plasmids can also contribute to strain typing and characterization.

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Terima kasih

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