Prebiotics & Probiotics PDF

Prebiotics, probiotics and next generation pharmaceutical modulation of the gut microbiome Deniz SERTEL, PhD.  There is no universally beneficial, «magic bullet» diet Healthy microbiota Modulation of the microbiota...

Prebiotics, probiotics and next generation pharmaceutical modulation of the gut microbiome Deniz SERTEL, PhD.  There is no universally beneficial, «magic bullet» diet Healthy microbiota Modulation of the microbiota Health by dietary approaches or therapeutic interventions is possible Healthy diet Modulation of the gut microbiota Therapetic strategies to modulate gut microbiota include: Prebiotic Probiotic Synbiotic FMT Phage miRNA…  Whether the need for the modulation of the gut microbiota is to prevent a specific disease or to treat an active disease? Is the individual predisposed to that disease? What are the possible risks? Probiotic Probiotics are live micro-organisms that, when administered in adequate amounts, confer a health benefit on the host. Mainly used for restoring/establishing a balanced microbiota Pathogens: beneficial microorganisms Human probiotic microorganisms belong mostly to the following geni: Lactobacillus, Bifidobacterium, and Lactococus, Streptococcus, Enterococcus, Bacillus and Saccharomyces Selection criteria of probiotic strains Probiotic microorganisms used in human nutrition Mechanisms of beneficial effects The basics of the beneficial effect of probiotics, involve : 1) Antagonism through the production of antimicrobial substances; 2) Competition with pathogens for adhesion to the epithelium and for nutrients; 3) Immunomodulation of the host; 4) Positive effects on metabolism; 5) Inhibition of bacterial toxin production. Probiotics and inflammatory bowel diseases Ulcerative colitis: Clinical studies have demonstrated that probiotics lead to the remission of ulcerative colitis. Crohn’s disease: no positive effect lactose intolerance: increased lactose digestion and tolerance significantly decrased diarrhoea and flatulance irritable bowel syndrome: significant improvement in symptoms (bloating, abdominal pain, constipation, abdominal cramps, and flatulence) Probiotics and cancer Animal studies have shown that probiotics may reduce the risk of colorectal carcinoma. However same effects has not been confirmed in clinical trials. Nonetheless, probiotics have been shown to alleviate gastrointestinal disorders in patients with cancer Improvement in the integrity of gut mucosal barrier, reduction in incidence of diarrhoea, less abdominal discomfort, etc. Probiotics and diarrhoea & intestinal infections The application of Saccharomyces boulardii yeast to patients with acute, watery diarrhoea resulted in the cure and reduced frequency of that type of complaints in two subsequent months. The efficacy of probiotic strains in the therapy of nosocomial, non- nosocomial, and viral diarrhoeas has also been documented. It turns out that probiotics may increase the amount of IgA antibodies, which leads to the arrest of a viral infection. Antibiotic-associated diarrhoea (AAD) and Clostridium difficile disease (CDD): In a meta analysis, 3 types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of AAD. Only S. boulardii was effective for CDD. Probiotics and extraintestinal infections Probiotic usage have been shown to have a positive effect on prevention of vaginitis. Studies demonstrated that the regular use of probiotics resulted in a reduced number of respiratory tract infections. Significant reduction of pulmonary exarbations with probiotic administration have been shown in childeren with cystic fibrosis Probiotics were associated with a significant reduction in nosocomial infections including VAP Probiotics and metabolic disorders Probiotic administration resulted in a reduction in BMI, arterial BP, CRP values and improvement in lipid profile and insulin sensitivity in obese patients. Significant reduction in blood glucose, HbA1C, LDL and total cholesterol was observed T2D patients recieving probiotics Probiotics and atopic dermatitis (eczema) Probiotic administration to pregnant women and their infants resulted in a substantial reduction in the cumulative prevalence of eczema in infants. When probiotics applied to childeren with AD, significant reduction in the severity of AD with an improved ration of IFN-γ and IL-10 was observed. In recent randomized controlled trials: Probiotic supplementation have been shown to have beneficial effects in preventing diarrhoea, necrotising enterocolitis, ulserative colitis, acute upper respiratory tract infections, pulmonary exacerbations in children with cystic fibrosis, and eczema in children. Probiotics also seem to improve cardiometabolic parameters and reduced serum concentrationof CRP in patients with type 2 diabetes. (In the trials mentioned above the probiotic type or dose and length of intervention is not matched) Prebiotics Food components or ingredients that are not digestible by the human body but specifically or selectively nourish beneficial colonic micro-organisms. Prebiotics may be used as an alternative to probiotics or as an additional support for them. Prebiotic selection criteria: Resistance to digestion in the upper GIT Fermentation by gut microbiota Beneficial effects on host’s health Selective stimulation of growth of probiotics Stability in varios food/feed processing conditions  Fruit, vegetables, cereals, and other edible plants are sources of carbohydrates constituting potential prebiotics. The majority of identified prebiotics are carbohydrates of various molecular structures, naturally occurring in human and animal diet. Carbohydrates, such as dietary fibre, are potential prebiotics. But not all dietary fibre can be considered as a prebiotic. Prebiotics are fermented by strictly defined groups of microorganisms and dietary fibre is used by the majority of colonic microorganisms Common prebiotics used in human nutrition are: Fructooligosaccharides (FOS), galactooligosaccharides (GOS), Inulin, xylooligosaccharides (XOS), lactitol, lactosucrose, lactulose, soy oligosaccharides, transgalactooligosaccharides (TOS)  Fermentable dietary fibres in the form of inulin, oligofructose, FOS,or galacto- oligosaccharides Increase the abundance of Bifidobacterium and Lactobacillus in stool samples (with Bifidobacterium spp. being associated with an increase in SCFAs) across several age groups and medical conditions. Health benefits of prebiotics The presence of prebiotics in the diet may lead to numerous health benefits Prevention of carcinogenesis, reduction of the blood LDL (low-density lipoprotein) level, stimulation of the immunological system, increased absorbability of calcium, maintenance of correct intestinal pH value.  The mechanism of a beneficial effect of prebiotics on immunological functions remains unclear. Several possible models have been proposed: (1) Prebiotics are able to regulate the action of hepatic lipogenic enzymes by influencing the increased production of short-chain fatty acids (SCFAs), such as propionic acid. (2) The production of SCFAs (especially of butyric acid) as a result of fermentation was identified as a modulator of histone acetylation, thus increasing the availability of numerous genes for transcription factors. (3) The modulation of mucin production. (4) It was demonstrated that FOS and several other prebiotics cause an increased count of lymphocytes and/or leukocytes in gut-associated lymphoid tissues (GALTs) and in peripheral blood. (5) The increased secretion of IgA Synbiotics Prebiotics + Probiotics The principal purpose of the combination is the improvement of survival of probiotic microorganisms in the gastrointestinal tract. In addition, stimulation of the proliferation of specific native bacterial strains present in the gastrointestinal tract is aimed. There are indications in the literature that, due to the use of prebiotics, probiotic microorganisms acquire higher tolerance to environmental conditions, including: oxygenation, pH, and temperature in the intestine of a particular organism Examples of prebiotics and synbiotics used in human nutrition Beneficial effects of synbiotics Synbiotics have the following beneficial effects on humans: (1) Increased Lactobacillus and Bifidobacterium genus count and maintenance of balance of the intestinal microbiota; (2) Improved hepatic function in patients suffering from cirrhosis; (3) Improved immunomodulative abilities; (4) Prevention of bacterial translocation and reduced incidence of nosocomial infections in patients’ post-surgical procedures and similar interventions Examples of clinical trials regarding the effect of synbiotics on human health Metabolites The gut microbiota-associated metabolites are pivotal regulators in the development and progression of many human diseases, and also are one of the novel therapeutic strategies. Metabolites are actually used in the treatment of local inflammation and in the modulation of cardiometabolic and neurological disorders, as well as cancers. Their properties make these metabolites relevant therapeutic candidates: natural bioavailability, high concentrations, easy administration, and tissue tolerability  SCFAs have been shown to exhibit anti-inflammatory effects, as previously discussed, in modulation of many local and systemic disorders, such in the gut-brain axis. The oral administration of SCFAs can alleviate the severe symptoms of brain-associated inflammatory encephalitis, and the auto-immune multiple sclerosis. Particularly, ingestion of butyrate not only suppressed the demyelination, but also triggered the remyelination, along with facilitating oligodendrocyte differentiation in mice with induced multiple sclerosis. Colon-delivered SCFAs can attenuate hypothalamic–pituitary–adrenal axis reactivity to psychosocial stress, suggesting hereby that SCFA supplementation alleviates mood alterations induced by repeated psychosocial stress. Other novel approaches miRNAs miRNAs are critical for maintenance of homeostasis, and have been known for decades for their role in the posttranscriptional regulation of gene expression at the cellular level. Hyaluronan an unbranched glycosaminoglycan (GAG) component of the extracellular matrix promotion and resolution of IBD by controlling recruitment of immune cells Nanomaterials to alter the cancer-causing dysbiotic microorganisms as well as their metabolites found in the cancer microenvironment