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                                   Prebiotics (Oligosaccharides)  

                                         Andrew Ying-Siu Lee, MD,PhD.

 

                                                           Microbiota of gut

-         Human colonic microflora is complex and metabolically-active ecosystem with central role in health and disease.

-     Human gut microbiome =   total number of genes encoded by all bacterial genomes of microbiota.  Gut microbiome

                                                       contain > 100 times the number of genes in our genome.

-         At birth, gut is sterile, but rapidly colonized after birth.  Colonization also occurs in mucosal surfaces of skin, airways,

      urogenital tract

-         Factors influencing microbiota of gut :-

      1. diet (eg. high-fat, high-protein and high-calorie diet reduce beneficial bacteria and increase virulent bacteria)

      2. host health and age. aged people have reduced beneficial bacteria

      3. host genotype and physiology

      4. immunity (IgA)

      5. diseases (eg. obesity has increased virulent bacteria and decrease beneficial bacteria)

      6. others such as hormones, pH, peristalsis, nutrient availability, oxidation-reduction potentials, host health and age,

          bacterial adhesion and cooperation, bacterial antagonism and transit time, mucin secretions containing

          immunoglobulins , sanitary conditon, air pollution etc.

-         Majority of bacteria in colon are anaerobes and derive energy from fermentation.  Main substrate = dietary non-digestible

      carbohydrates (eg. oligosaccharides)

 

-         Importance of beneficial bacteria in gut:-

1.        maintain mucosal immune system

2.        maintain normal physiological environment

3.        provide essential nutrients and vitamins

4.        inhibiting virulent bacteria thereby toxin formation, pathogenicity and carcinogenesis. For example, in stomach,

       H. pylori --> gastritis, peptic ulcer and gastric carcinoma. In small intestine, E.Coli, salmonella.

In large intestine, clostridium, enterocci.

5.    possess many metabolic capabilites which are lacking in the host and thus indispensable for human life.

 

                       Probiotics, Prebiotics & Synbiotics

Probiotics = microbes with benefit (eg. lactobacilli, bifidobacteria)

Prebiotics = dietary component that stimulate growth and/or activity of probiotics

Synbiotics = probiotic + prebiotic

 

-         Non-digestible oligosaccharides =  preferred prebiotics.  Including:  isomalto-oligosaccharides, fructo-oligosaccharides,

      inulin-type fructans, nannan-oligosaccharides, galacto-oligosaccharides, soy-bean oligosaccharides (raffinose and

      stachyose), xylo-oligosaccharides, gluco-oligosaccharides.

-         Isomalto-oligosaccharides significantly increase number of protective gut microflora.

-         Food contains only trace levels of prebiotics

-     Prof. Tomotari Mitsuoka, pioneer in microecology, reported that isomalto-oligosaccharides (with high pannose

      concentration) dramatically increased bifidobacteria in gut.

 

                                                 Prebiotics as antipathogens

-         Prebiotics promote beneficial bacteria (bifidobacteria and lactobacilli) and inhibit virulent bacteria

      (enteropathogenic E. Coli etc) in gut

-         Beneficial bacteria produce antimicrobial substances, bacteriocins and antibiotic-like substances, and 

      facilitate degradation of toxin receptors.

-         Prebiotics reduce gut infections such as acute infectious gastroenteritis, irritable bowel syndrome, inflammatory

      bowel disease (ulcerative colitis and Crohn's disease), and respiratory tract infections.

 

                                           Prebiotics in glucose homeostasis

-         improve glucose tolerance and glycemic response by increasing insulin secretion or insulin sensitivity

-         increase secretion of GLP (=gut peptide),  increase beta cell differentiation and insulin secretion.  Other metabolic

      mechanisms such as decrease in inflammatory tone  also contribute to improvement of glucose homeostasis.

 

                                             Prebiotics in lipid homeostasis

-         modulate hepatic lipid metabolism and serum lipids due to decrease in do novo lipogenesis in liver

 

                                           Prebiotics in mineral metabolism

-         enhance calcium, Mg, Fe, Zn, Cu absorption by trophic effect on gut (cell growth and functional enhancement of

      absorptive area)

-         stimulate intestinal calcium absorption due to progressive decrease in cecal or ileal pH, hypertrophy of cecal walls and

      rise of cecal pool of SCFA.

                                               Prebiotics in obesity

-         Regulate food intake and weight gain, as well as metabolic disorders associated with obesity such as liver steatosis,

      dyslipidemia, diabetes, hypertension.

-         Endocrine cells in intestinal mucosa secrete GI peptides (gut hormones) involved in regulation of energy homeostasis

      eg. glucagon-like peptide, peptide Y, ghrelin, oxyutomodulin,anorexigenic peptides GLP and PYY, so as to regulate

      food intake and decrease fat mass.

-         Promote satiety, reduce hunger, appetite regulation

-         Maintenance of appropriate body weight (BMI) and fat mass in young adolescents.

-         Gut hormone modulation in management of obesity and metabolic syndrome in human.  Clinical trial reported decrease

      food intake,body weight gain and fat mass development in obese subjects.

 

                                             Prebiotics in inflammation

-         Differences in specific healthy bacteria in gut microbiota may precede development of obesity.  Harmful bacteria trigger

      low-grade inflammation contributing to development of obesity

-         Prebiotics inhibit TGF-induced fibrogenic activity (profibrogenic cytokine transforming growth factor) in pulmonary fibrosis in rat

 

                                         Prebiotics in immunomodulation

-         Prebiotics improve resistance against infections, allergies and inflammation

-         Prebiotics modulate immune system .  Microbiota is essential for optimal structural and functional development

      of immune system.  Gut-associated lymphoid tissues provide cytokines to defense against intestinal pathogens

      and commensal microbes. 

-         Prebiotics reduce risk of allergies by decreasing IgE and IgG levels

-         Prebiotics stimulate intestinal and systemic immunity

-         Prebiotics --> increase IgA production in infants

-         In infants, prebiotics decrease diarrhea, atopic eczema

-         In elderly, prebiotics increase phagocytosis, NK cell activity and anti-inflammatory cytokines, and reduce production

      of proinflammatory cytokines.

                                                 Prebiotics in Cancer

-         Colonic microbiota involved in colon cancer due to bacterial metabolism and endogenous secretions.  In liver cancer, number

      of beneficial bacteria (bifidobacteria and lactobacili) decrease whereas that of virulent bacteria (E.Coli and enteroccoci) increase

-         Gut virulent bacteria generate wide variety of mutagens, carcinogens, tumor promotors including N-nitrosocompounds,

      secondary bile acids, ammonia, phenols and cresols from dietary and endogenously produced precursors.

-         Prebiotics inhibit harmful bacteria, thereby decrease in toxic substances, cancer biomarkers, DNA and oxidative damage

      in colon mucosa of polyp patients.

-         Prebiotics produce anticancer metabolites, protective enzymes and up-regulation of apoptosis, resulting in lower adenoma

      and adenocarcinoma incidence.

 

                                                                          Others

-     Prebiotics as antioxidants, prevent dental caries, radiation damage, and promote nutrient absorption, angiogenesis

-     Prebiotics increase fecal and mucosal bifidobacteria and secretion of gut peptides

-         Prebiotics increase biomass and stool bulking preventing constipation

-         Prebiotics enhance absorption of nutrients, minerals and vitamins.

-         Prebiotics increase production of short-chain fatty acids, which is energy source, lower hepatic synthesis of cholesterol, mucosa

      regeneration, metabolism of colonic epithelial cells, trophic effects on intestinal epithelia and immune structure and function

-        Prebiotics increase serum growth hormone, insulin-like growth factor, mRNA and protein synthesis, antifungal and antimicrobial

      activity that improve gut health, lower lipids,improve whole body protein anabolism.

-         Prebiotics improve performance and health status

-     Prebiotics improve neuropsychological tests and memory function, improve hematological and biochemical variables in man.

-         Prebiotics decreased serum ammonia, endotoxin, GPT, alphaGP, HA, LN, IV-C, TNF alpha in liver cirrhosis patients

-    Prebiotics activate macrophage (for defense mechanism), and produce nitric oxide (for vasodilatation)

-    Prebiotics promote human urogenital tract defense mechanisms.

 

Prebiotics definitely promote health !

Since prebiotics are readily hydrolyzed by small intestinal enzymes,

which preparation to use?

Isomalto-oligosaccharide (with high pannose concentration) is a good choice !