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Probiotics

T
Teja Naveen

This document defines probiotics and discusses their mechanisms of benefit. It outlines common probiotic strains and characteristics of effective probiotics. The document also discusses the human microbiome and how diet influences microbiome composition. It reviews evidence on using probiotics to treat various conditions like diarrhea, IBD, and C. difficile infection. Next generation probiotics under research include strains of L. reuteri that produce antimicrobial compounds.

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PROBIOTICS -TEJA NAVEEN
DEFINITION 1. WHO de鍖nes Probiotics as Live micro organisms which when administered in adequate amounts confer a health bene鍖t on the host 2. Lactobacillus species L. Acidophilus L.casei (rhamnosus) L.reuteri L.salivarius L.Plantarum Bifidobacterium species B.bi鍖dum B.longum B.breve B.infantis B.lactis Others Saccharomyces boulardii Non pathogenic E.coli S.thermophilus Clostridium butyricum
MECHANISMS OF BENEFIT 1. Bene鍖ts of probiotics are incompletely understood 2. Suppression of growth or epithelial binding/invasion by pathogenic bacteria 3. Improvement of intestinal bacterial function 4. Modulation of the immune system 5. Modulation of pain perception
1. Some of the commercially available probiotics include: 2. VSL#3 (Bi鍖dobacterium breve,B.longum,B.infantis,Lactobacillus acidophillus,L.plantarum,L.paracasei,L.bulgaricus,streptococcus thermophilus) 3. Align(B.infantis) 4. Culturelle(L.rhamnosus GG) 5. DanActive(L.casei) 6. Muta鍖or(E.coli Nissle 1917) 7. Florastor(s.boulardii)
CHARACTERISTICS OF EFFECTIVE PROBIOTICS 1. Able to survive the passage through the digestive system 2. Able to attach to the intestinal epithelial and colonise 3. Able to maintain good viability 4. Able to utilise the nutrients and substrates in a normal diet 5. Non pathogenic and non toxic 6. Stability of desired characteristics during processing,storage and transportation 7. Anti-in鍖ammatory,antimutagenic,immunostimulatory
MICROBIOTA AND MICROBIOME 1. Healthy adult harbours~ 100 trillion bacteria in gut alone 2. This is 10x the number of human cells we possess 3. Humans possess 23,000 genes 4. Microbiota contributes ~33,00,000 5. Communal gut microbial genome (microbiome) is ~150 times larger than human genome 6. Is dominated by 4 large groups of bacteria or phyla: Actinobacteria,Bacteroidetes,Firmicutes,Proteobacteria
Probiotics
Probiotics
Probiotics
Probiotics
1. Bacteria express glycoside hydrolyse which converts glycans into useable sugars 2. No enzyme encoded in human genome is capable of digesting glycans -only bacterial enzymes 3. Many carbohydrates are digestible only by bacteria and produce SCFA-primary fuel for colonocytes 4. 10-15% of adult energy may be generated by SCFA production
Probiotics
Probiotics
1. PREBIOTICS- Nondigestable carbohydrates that stimulate the growth and activity of bene鍖cial colonic bacteria 2. Best source of prebiotic 鍖ber are Inulin and oligosaccharides(fructooligosaccharides and galactooligosaccharides) 3. Traditional dietary sources of PREBIOTICS include soybeans,raw oats,unre鍖ned wheat and barely 4. When these are metabolised by gut microbes,short chain fatty acids are produced 5. SCFs nourish cells that line the gut 6. Reduces the risk for cancer in the gut 7. Enhance calcium absorption and relieve constipation and diarrhoea 8. SYNBIOTICS- Mixture of Pro and PREBIOTICS
DIET INFLUENCES MICROBIOME COMPOSITION Long term diet is associated with development of speci鍖c Enterocytes 1. Diets high in animal protein and fat with high levels of Bacteroides and low levels of Prevotella 2. Diets high in carbohydrates but low in animal protein and fat with higher levels of prevotella butvlower levels of Bacteroides Japanese harbour organisms that produce enzyme that aids in sea weed digestion Microbiota of African children enriched in Bacteroides and depleted in Firmicutes to maximize energy uptake from 鍖bre rich diet.
Probiotics
Probiotics
REVERSING DYSBIOSIS 1. Colectomy 2. Colon cleaning 3. Antibiotics 4. Prebiotics 5. Probiotics 6. Faecal transplantation
ALLERGIC DISEASES 1. Studies have shown di鍖erences in the early colonisation patterns of infants who develop allergic disease 2. Low levels of Bi鍖dobacterium and early colonisation with potentially pathogenic bacteria,such as Clostridioides(formerly clostridium) di鍖cile and staphylococcus aureus, were more prevalent in children who subsequently developed allergy 3. High diversity of Microbiota is required for immune system maturation,which is less in allergic patients 4. World Allergy organisation suggests use of PREBIOTICS only in infants who are not exclusively breastfed and probiotics in pregnant and lactating women and in infants when there is high risk of allergy in the children
1. CONSTIPATION- Improvement in defecation frequency ,stool consistency,and intestinal transit time with Bi鍖dobacterium lactis DN-173 010,B.lactis BB12,Lactobacillus casei Shirota,L.reuteri DSM 19738 and E.coli Nissle 1917. 2. Should be avoided in management of severe constipation in elderly and in children with functional constipation 3. PANCREATITIS- Probiotics did not reduce the risk of infectious complications and actually increased mortality from mesentric ischemia. 4. LACTOSE INTOLERANCE: Lactose fermenting Lactobacillus acidophilus strain showed reduced symptoms after in vivo lactose challenge
DIARRHEAL ILLNESSES 1. Infectious diarrhoea- May be considered for use in children and adults.It reduces the duration of diarrhoea 2. In acute rotavirus diarrhoea in children ,VSL#3 signi鍖cantly decreased stool frequency. 3. Lactobacillus GG showed a dose dependent decrease in fecal shedding of rotavirus 4. Protective mechanisms include strengthening the mucosal barrier,blocking viral entry,decreased viral toxin expression,and inducing antiviral IgA. 5. A combination of seven Lactobacillus,Bi鍖dobacterium, and streptococcus thermophilus signi鍖cantly decreased acute dysentery bleeding and hospitalisation. 6. Celiac diseases- No evidence to support the use of probiotics in patients with celiac disease
Clostridioides(formerly clostridium) di鍖cle infection 1. Probiotics when given with antibiotics,there is 60% risk reduction in development of clostridium di鍖cle associated diarrhoea 2. No enough evidence to support use of probiotics in treating clostridium di鍖cile infection 3. Pouchitis-Study of patients with pouchitis showed persistence of Fusobacteria and enteric species,increased clostridium perfringens,and the absence of streptococcus species 4. VSL#3 found more e鍖ective for preventing relapse of chronic pouchitis and prevention onset of pouchitis
FECAL TRANSPLANTATION 1. First performed in 1958 for fulminant pseudomembranes 2. Now accepted as e鍖ective for recurrent C.di鍖cile 3. 92% e鍖ective when standard therapy failed 4. Administered by NG,NJ,enema or colonoscopy 5. E鍖cacy slightly improved with antibiotics before Microbiota transplantation
INFLAMMATORY BOWEL DISEASE 1. Various probiotic species have shown promise in the treatment of ulcerative colitis,but these studies are done in small no of patients and no strong conclusions in systematic reviews 2. E. coli 1917 Nissle was shown to be as e鍖ective as low dose 5-ASA in preventing relapse 3. Lactobacillus GG appeared to be more e鍖ective than standard treatment involving mesalazine in prolonging relapse free time,but did not in鍖uence relapse rates 4. Combination of a prebiotic and a probiotic(B.longum) was associated with improvement in histological scores 5. Crohn disease- Available data do not support clinical e鍖ectiveness of probiotic therapy for either induction or maintenance of remission
Probiotics
NEXT GENERATION PROBIOTICS 1. These come from the human intestinal microbes and include novel bacteria that have not been previously used as health promoting agent. 2. L.reuteri produces an antibacterial compound from glycerol called reuterin and this can eliminate clostridium di鍖cile. 3. It has also got antibiotic resistance properties,so this can be used in recurrent c.di鍖cile infection in addition to antibiotics

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Probiotics

  • 2. DEFINITION 1. WHO de鍖nes Probiotics as Live micro organisms which when administered in adequate amounts confer a health bene鍖t on the host 2. Lactobacillus species L. Acidophilus L.casei (rhamnosus) L.reuteri L.salivarius L.Plantarum Bifidobacterium species B.bi鍖dum B.longum B.breve B.infantis B.lactis Others Saccharomyces boulardii Non pathogenic E.coli S.thermophilus Clostridium butyricum
  • 3. MECHANISMS OF BENEFIT 1. Bene鍖ts of probiotics are incompletely understood 2. Suppression of growth or epithelial binding/invasion by pathogenic bacteria 3. Improvement of intestinal bacterial function 4. Modulation of the immune system 5. Modulation of pain perception
  • 4. 1. Some of the commercially available probiotics include: 2. VSL#3 (Bi鍖dobacterium breve,B.longum,B.infantis,Lactobacillus acidophillus,L.plantarum,L.paracasei,L.bulgaricus,streptococcus thermophilus) 3. Align(B.infantis) 4. Culturelle(L.rhamnosus GG) 5. DanActive(L.casei) 6. Muta鍖or(E.coli Nissle 1917) 7. Florastor(s.boulardii)
  • 5. CHARACTERISTICS OF EFFECTIVE PROBIOTICS 1. Able to survive the passage through the digestive system 2. Able to attach to the intestinal epithelial and colonise 3. Able to maintain good viability 4. Able to utilise the nutrients and substrates in a normal diet 5. Non pathogenic and non toxic 6. Stability of desired characteristics during processing,storage and transportation 7. Anti-in鍖ammatory,antimutagenic,immunostimulatory
  • 6. MICROBIOTA AND MICROBIOME 1. Healthy adult harbours~ 100 trillion bacteria in gut alone 2. This is 10x the number of human cells we possess 3. Humans possess 23,000 genes 4. Microbiota contributes ~33,00,000 5. Communal gut microbial genome (microbiome) is ~150 times larger than human genome 6. Is dominated by 4 large groups of bacteria or phyla: Actinobacteria,Bacteroidetes,Firmicutes,Proteobacteria
  • 11. 1. Bacteria express glycoside hydrolyse which converts glycans into useable sugars 2. No enzyme encoded in human genome is capable of digesting glycans -only bacterial enzymes 3. Many carbohydrates are digestible only by bacteria and produce SCFA-primary fuel for colonocytes 4. 10-15% of adult energy may be generated by SCFA production
  • 14. 1. PREBIOTICS- Nondigestable carbohydrates that stimulate the growth and activity of bene鍖cial colonic bacteria 2. Best source of prebiotic 鍖ber are Inulin and oligosaccharides(fructooligosaccharides and galactooligosaccharides) 3. Traditional dietary sources of PREBIOTICS include soybeans,raw oats,unre鍖ned wheat and barely 4. When these are metabolised by gut microbes,short chain fatty acids are produced 5. SCFs nourish cells that line the gut 6. Reduces the risk for cancer in the gut 7. Enhance calcium absorption and relieve constipation and diarrhoea 8. SYNBIOTICS- Mixture of Pro and PREBIOTICS
  • 15. DIET INFLUENCES MICROBIOME COMPOSITION Long term diet is associated with development of speci鍖c Enterocytes 1. Diets high in animal protein and fat with high levels of Bacteroides and low levels of Prevotella 2. Diets high in carbohydrates but low in animal protein and fat with higher levels of prevotella butvlower levels of Bacteroides Japanese harbour organisms that produce enzyme that aids in sea weed digestion Microbiota of African children enriched in Bacteroides and depleted in Firmicutes to maximize energy uptake from 鍖bre rich diet.
  • 18. REVERSING DYSBIOSIS 1. Colectomy 2. Colon cleaning 3. Antibiotics 4. Prebiotics 5. Probiotics 6. Faecal transplantation
  • 19. ALLERGIC DISEASES 1. Studies have shown di鍖erences in the early colonisation patterns of infants who develop allergic disease 2. Low levels of Bi鍖dobacterium and early colonisation with potentially pathogenic bacteria,such as Clostridioides(formerly clostridium) di鍖cile and staphylococcus aureus, were more prevalent in children who subsequently developed allergy 3. High diversity of Microbiota is required for immune system maturation,which is less in allergic patients 4. World Allergy organisation suggests use of PREBIOTICS only in infants who are not exclusively breastfed and probiotics in pregnant and lactating women and in infants when there is high risk of allergy in the children
  • 20. 1. CONSTIPATION- Improvement in defecation frequency ,stool consistency,and intestinal transit time with Bi鍖dobacterium lactis DN-173 010,B.lactis BB12,Lactobacillus casei Shirota,L.reuteri DSM 19738 and E.coli Nissle 1917. 2. Should be avoided in management of severe constipation in elderly and in children with functional constipation 3. PANCREATITIS- Probiotics did not reduce the risk of infectious complications and actually increased mortality from mesentric ischemia. 4. LACTOSE INTOLERANCE: Lactose fermenting Lactobacillus acidophilus strain showed reduced symptoms after in vivo lactose challenge
  • 21. DIARRHEAL ILLNESSES 1. Infectious diarrhoea- May be considered for use in children and adults.It reduces the duration of diarrhoea 2. In acute rotavirus diarrhoea in children ,VSL#3 signi鍖cantly decreased stool frequency. 3. Lactobacillus GG showed a dose dependent decrease in fecal shedding of rotavirus 4. Protective mechanisms include strengthening the mucosal barrier,blocking viral entry,decreased viral toxin expression,and inducing antiviral IgA. 5. A combination of seven Lactobacillus,Bi鍖dobacterium, and streptococcus thermophilus signi鍖cantly decreased acute dysentery bleeding and hospitalisation. 6. Celiac diseases- No evidence to support the use of probiotics in patients with celiac disease
  • 22. Clostridioides(formerly clostridium) di鍖cle infection 1. Probiotics when given with antibiotics,there is 60% risk reduction in development of clostridium di鍖cle associated diarrhoea 2. No enough evidence to support use of probiotics in treating clostridium di鍖cile infection 3. Pouchitis-Study of patients with pouchitis showed persistence of Fusobacteria and enteric species,increased clostridium perfringens,and the absence of streptococcus species 4. VSL#3 found more e鍖ective for preventing relapse of chronic pouchitis and prevention onset of pouchitis
  • 23. FECAL TRANSPLANTATION 1. First performed in 1958 for fulminant pseudomembranes 2. Now accepted as e鍖ective for recurrent C.di鍖cile 3. 92% e鍖ective when standard therapy failed 4. Administered by NG,NJ,enema or colonoscopy 5. E鍖cacy slightly improved with antibiotics before Microbiota transplantation
  • 24. INFLAMMATORY BOWEL DISEASE 1. Various probiotic species have shown promise in the treatment of ulcerative colitis,but these studies are done in small no of patients and no strong conclusions in systematic reviews 2. E. coli 1917 Nissle was shown to be as e鍖ective as low dose 5-ASA in preventing relapse 3. Lactobacillus GG appeared to be more e鍖ective than standard treatment involving mesalazine in prolonging relapse free time,but did not in鍖uence relapse rates 4. Combination of a prebiotic and a probiotic(B.longum) was associated with improvement in histological scores 5. Crohn disease- Available data do not support clinical e鍖ectiveness of probiotic therapy for either induction or maintenance of remission
  • 26. NEXT GENERATION PROBIOTICS 1. These come from the human intestinal microbes and include novel bacteria that have not been previously used as health promoting agent. 2. L.reuteri produces an antibacterial compound from glycerol called reuterin and this can eliminate clostridium di鍖cile. 3. It has also got antibiotic resistance properties,so this can be used in recurrent c.di鍖cile infection in addition to antibiotics