PROBIOTICS AND ANTIMICROBIALS

SynbioticsDefinition

• A probiotic organism in combination with its prebiotic food

• Providing both the organism and substrate at the time of ingestion may offer improved chance of survival in GI tract

Dysbiosis

• Dysbiosis is an intestinal imbalance where pathogenic microorganisms outnumber beneficial bacterial species.

• Digestive diseases are often caused in part by or result in dysbiosis.

PrebioticsDefinition

• Nondigestible food ingredients– Fructo-oligosaccharides (chicory, inulin)– Lactulose

• Positively affect the endogenous flora• Stimulate the growth of one or a limited

number of bacterial species– FOSBifidobacteria– LactuloseLactobacilli

ProbioticsDefinition

• Nutritional supplement• Contains 1 or more

cultures of living organisms – Typically bacteria or

yeast• Modify the endogenous

microflora• Have a positive effect on

the host

"live microorganisms which when administered in adequate amounts confer a health benefit on the host."

ProbioticsCandidates

• Lactobacillus– acidophilus, reuteri, casei, planatarum,

rhamnosus “GG”

• Bifidobacteria– bifidum, breve, infantis, longum

• Streptococcus– thermophilus

• Saccharomyces• Several combinations on the market

Probiotics Potential Mechanisms of Action

• Inhibition of adhesion• Immunomodulation• Production of antimicrobial substances• Modification of toxins or toxin receptors• Competition for nutrients• Reduction in bacterial translocation• Anti-inflammatory signaling within the

epithelium

PREBIOTICS

Supplements not digested by human enzymes that stimulate growth of beneficial bacteria

• Fructo-oligosaccharides• Inulin• Galacto-,galactosyllactose-,xylo-,isomalto-and

soya oligosaccharides• Pyrodextrins (glucose oligosaccharides)• Lactulose• Breast milk oligosaccharides

Oligosaccharides

• Usual pleasant slight sweet taste

• Add texture to foods

• Naturally occurs in artichoke, onion,garlic, chicory, leek, and to a lesser degree in cereals

• Raffinose and stachynose are major CHO of beans and peas

• Commercially produced (FOS)

Benefits of Oligosaccharides

• Promote the growth of bifido-and lactobacilli

• Lower colon pH

• Discourage growth of Clostridia

• Prevent constipation and diarrhea

• Have low glycemic index

• Water-soluble and of low viscosity

• Do not bind minerals

Inulin

• Naturally occurs in fruits and vegetables

• Longer chain length than FOS

• Provides a fat mimicking texture when added to food

• Now available in a supplement

Bifidobacteria

• At least 4g/day of FOS are needed to increase counts

• Effect increases with increased doses

• Ferment oligosaccharides to SCFA

• Produce B vitamins and some amino acids

• Restore flora after antibiotics

• Inhibit the growth of pathogenic bacteria

PROBIOTICS

Lactobacillus acidophilusFloch,Gastro Clin NA 2005;34:517 : Huebner Gastro Clin NA 2006 :35;355

Elie Metchnikoff

• 1845-1916 , Nobel Prize Winner• Phagocytosis and Ageing• “Intoxication from the gut flora”• Putrefactive bacteria produced toxic substances

absorbed from the gut affecting the nervous and vascular systems causing ageing

• His radical solution for autointoxication was removal of the flora by colectomy

• Another approach was to replace putrefactive bacteria with carbohydrate fermenting bacteria

PROBIOTICS

• Live microbial food supplements which beneficially affect the host animal by improving its intestinal microbial balance.

• Usually strains of bacteria (lactobacilli or bifidobacteria) or yeasts (Saccharomyces)

• Administered in yogurts or capsules

• Survive passage thru the gut

PROPERTIES of PROBIOTICS

• Human origin• Resist upper GI tract secretions• Adhere to human intestinal cells• Colonize the human intestinal tract• Production of antimicrobial substances• Antagonize carcinogenic/ pathogenic flora • Safe in clinical use at > 1010

• Stimulate immune process• Fermentation

Dose of Probiotic

• Varies greatly with product

• Live and active cultureYogurts must contain >108 [100 million]

• L.rhamnosus GG has 10 billion

• VSL#3 has 300 to 450 billion per packet

• Common OTC have millions

IMMUNOREGULATION (A/B)

• Increase IgA production• Increase anti-rotaviral IgA• Production of gamma intereferon, TNF-

alph,IL-1 by mononuclear cells incubated with Lactobacillus.

• Adherant Lactobacilli and Bifidobacteria significantly increase phagacytosis.

• Lactobacillus GG has been used to treat cow milk allergy and atopic eczema

Probiotic Organisms in USE

• Bifidobactor sp. (bifidum, longum, breve,animalis, infantis,adolescentis)

• Streptoccus thermophilus

• Saccharomyces boulardii,cerevisiae

• Enerococcus faecium

• Lactobaciilli sp. (casei, acidophilus, bulgaricus, gaseri)

• L.rhamnosus, GG• Lactococcus sp.

(lactis,cremaris)

CLAIMS FOR PROBIOTICS

• Increase resistance to infection• Decrease duration of diarrhea disease• Stimulate immunity, modulate cytokine gene

expression, stimulate phagocytosis• Beneficial effect on blood pressure,serum

cholesterol, diabetes mellitus,lactose digestion and allergy

• Regression of tumors and reduction in carcinogens

Antibiotics

Trade name Active ingredientAureomycin chlortetracyclineTerramycin oxytetracyclineBacitracin bacitracinGallimycin gallimycinTylan tylosin

Common antibiotics used to promote growth, feed efficiency

steroids

• General classifications

– Estrogens – estradiol and estrone

– Non-steroidal compounds with estrogenic activity -diethylstilbestrol (DES) and zeranol

– Androgens – testosterone and trenbolone acetate (TBA)

– Progestagens – progesterone and melengestrol acetate (MGA)

– ß-adrenergic, ß agonists, repartitioning agents• lipolysis (fat mobilization), protein synthesis eg clenbuterol,

cimaterol ractopamine

Probiotics

• Lactobacillus sp.– reuteri– casei– ramnosus– acidophilus

• Streptococcus sp.• Bifidobacterium sp.

– infantis– lactis– longum– breve– bifidum

• Sacharomyces boulardii (non-human)

• VSL no.3

Dysbiosis

• Dysbiosis is an intestinal imbalance where pathogenic microorganisms outnumber beneficial bacterial species.

• Digestive diseases are often caused in part by or result in dysbiosis.

Dysbiosis

•Decreased immune function•Poor diet—excessive carbohydrates, sugar and trans fat•Drugs—especially antibiotics, oral contraceptives and cortisone-like medications

•Intestinal infection•Decreased intestinal motility (aka constipation)•Stress—including long-term emotional stress•Maldigestion and malabsorbtion

Major Causes

Dysbiosis

•Abdominal pain or cramps•Colon cancer•Constipation or diarrhea•Distention/bloating•Fatigue•Fatigue after eating•Flatulence

•Bad Breath•Body Odor•Food Allergy•Hypoglycemia•Inability to lose weight•Irregular bowel movements

•Irritable bowel syndrome•Itchy anus•Leaky gut syndrome•Poor complexion•Poor digestion•Rheumatoid arthritis•Spastic colon

Common Symptoms

Probiotics: Proposed uses

• Infectious diarrhea• Antibiotic-associated diarrhea• IBD, IBS, and pouchitis• Necrotizing Enterocolitis• Bacterial vaginosis• Recurrent UTI’s• Atopic diseases• Immune system enhancement• H pylori infections• Dental caries• Radiation induced diarrhea• Cardiovascular risk reduction• Constipation• Rheumatoid arthritis

Probiotics: proposed mechanisms

• Adherence and subsequent stimulation of gut immune system– Up-regulation of mucin gene– Enhance secretory IgA– Maintain normal macrophage function

• Competition for essential nutrients• Production of antimicrobial factors• Provide favorable environment for growth of other

beneficial bacteria• Production of short-chain fatty acids with anti-

inflammatory properties

Why should YOU care?

• Chemical farming and pesticides have lead to sterilization of soil and water (chlorination).

• Antibiotics, hormones, and other drugs are given to chickens and cattle used for food.

• Stress, medications, and typical American diet all promote dysbiosis.

Special Probiotics

• Homeostatic Soil Organisms (HSO’s) are specific probiotic strains of microorganisms found in the soil.

• In nature, HSO’s help plants digest inorganic substances, protect roots from parasites, yeast, and fungi, and provide growth factors and different hormones.

• When ingested orally in a probiotic formulation, may have advantages over non-HSO probiotic formulas, due to ability to implant and survive in the gut.