4/15/2018

The gut and pre and probiotics Candace Becker, APRN, CNS-BC, Rx, CHFH

Objectives:

 Review the gut pathophysiology and inflammatory process

 Investigate process of gut inflammation

 Discuss pre and probiotics and their influence on gut health

 Evaluate content of common pre and probiotics

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Definitions

 Probiotic – “for life”- nonpathogenic organisms that have no necessary phylogenic (evolutionary) reaction. Considered “good” bacteria that help keep digestive system healthy by controlling growth of harmful bacteria.

 Prebiotics - carbohydrates that cannot be digested by the human body, but feed probiotics; "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well being and health." They are dietary fibers with a well- established positive impact on the intestinal microflora.

 Microflora/microbiome - bacteria and microscopic organisms, especially those living in a particular site or habitat

Definitions (cont.)

 Symbiots – pre and probiotics designed to improve survival of ingested “live microorganisms which, when administered in adequate amounts, confer health benefit on host…”

 Commensal organisms -- Living in a relationship in which one organism derives food or other benefits from another organism without hurting or helping it.

 Dysbiosis - microbial imbalance or maladaptation on or inside the body

 Stress – anything that threatens homeostasis

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Some basics…

 GI tract is home to >500 bacterial species. Bacteria + virome = microbiota

 Microbiota are responsible for digestion, acquiring nutrients, immune system

 Bacterial cells outnumber human cells 10:1

 Some of the B vitamins, vitamin K, folate and short chain fatty acids are produced by gut bacteria

 Up to 10% daily energy needs come from gut fermentation

Yeast

Nutr Metab (London). 2010; 7:79

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Gut lining pathophysiology

 Normal microbial and yeast balance

 Process of protection and absorption

 Barrier function of gut to reduce apoptosis and/or increase mucin production

 Production of antimicrobial substances, such as defensins, bacteriocins, hydrogen peroxide, and short chain fatty acids which alters organisms membrane

 Competition for adherence to reduce bacterial influx into body

 Immune modulation (70% of immune function comes from gut) by increase IgA, down regulation of cytokines and chemokines

 Interference with quorum sensing signaling which reduces cell communication and reduces colonization

Barrier function

 Regulation of intestinal microbial homeostasis

 Reduced apoptosis

 Competition for adherence

 Alter ability of pathogens to colonize and infect mucosa

 Increased mucin production

 Interference with quorum sensing signaling >> decreases cell communication >> decreases colonization

 Stabilization/maintenance IG barrier function

 Production of antimicrobial substances (defensins, bacteriocins, H2O2, NO, short chain fatty acids) which alter organism membrane

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Good barrier function

Immunomodulatory response

Modulation of local and systemic immune responses by increased IgA, down regulation of cytokines and chemokines and adherance molecules, and up or down regulation of interleukin, interferon and tumor necrosis factor

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Major effects of stress on gut physiology

 alterations in gastrointestinal motility;

 increase in visceral perception;

 changes in gastrointestinal secretion;

 increase in intestinal permeability;

 negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and

 negative effects on intestinal microbiota.

Konturek, PC, Brzozowski, T, Konturek, SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. 2011 Dec 62(6)

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Is there a role for addition of probiotics for gut health/healing?

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Probiotic stats

 Growing global market; $21.6 billion in 2010, $35 billion in 2014, projected growth to $52 billion by 2020  Classified as supplements, thus less stringent requirements for safety, efficacy and purity. Not subject to FDA oversight. The European Union has banned the use of the word “probiotic” in marketing unless a product receives approval for a health claim. No such approvals have been granted.  Claims of improving digestive health, improved immunity, treatment of diabetes and obesity, treatment of inflammatory bowel disease, constipation, diarrhea, eczema, tooth decay

MOA probiotics

 postulated mechanisms of action of probiotics on stressed gastrointestinal mucosa include:  improvement of the barrier function  suppression of the growth and binding of pathogenic bacteria  immunomodulatory effect  positive effect on visceral hypersensitivity

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Common bacterial strains in probiotics

 Lactobacillus  Bifidobacterium  E coli Nissle 1917  Streptococcus species  Lactococcus lactix  Some enterococcus  Probiotic yeasts: saccharomyces boulardii

Common sources of pre and probiotics

 Active cultures

 Yogurt

 Acidophillus milk, Buttermilk

 Sauerkraut (unpasteurized), kimchi

 Sour pickles (no vinegar)

 Miso soup, tempeh

 Kombucha (bubble tea)

 Kvass (fermented drink made from beets)

 Sourdough bread

 Fermented soft cheese (cheddar, swiss, gouda, parmesan)

 Fiber

 Undigestible (pre-biotic) – apple cider vinegar, dark chocolate

 Supplements

 Available pill/capsule form (freeze dried)

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Common probiotics

Trade Name Manufacturer Comments Contains B. animalis lacis Bb-12 in addition to S. thermophilus abd L. Yo-Plus yogurt Yoplait Inc bulgaricus per serving. DanActive Contains S. thermophilus and L. bulgaricus in addition to L. casei DN-114 001. Dannon Inc Cultured milk Each serving contains 10 billion CFUs.

Contains B. breve, B. infantis, B. longum, L. acidophilus, L. bulgaricus, L. casei, VSL#3 packets Sigma-Tau Pharmaceuticals L. plantarum and Streptococcus thermophiles. Each packet contains 450 billion CFUs. Lemon flavored and is consumed by mixing in atleast 4 oz of cold water.

Includes Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9- Philips Colon Health capsules Proctor & Gamble 1 and Bifidobacterium longum MM-2. Each capsule contains 1.5 billions cells.

Florastor capsules Biocodax, inc Contains Saccharomyces boulardii. Each 250 mg capsule contains 5 billion CFUs. Florastor Kids Biocodex Inc Contains Saccharomyces boulardii. Available as powder. Contains Koshar Lactobacillus acidophilus NCFM, L. casei Lc- Attune nutrition bars Attune Foods 11 and Bifidobacterium lactis HN019. Contains 3g fiber. Each serving contains 6.1 billion CFUs. Contains Bifidobacterium infantis 35624 in a vegetarian capsule shell. Each Align capsules Proctor & Gamble capsule contains 1 billion bacteria. Contains Bacillus coagulans GBI-30, 6086 (BC30). Available as capsules, chewies Sustenex Schiff Nutrition International and gummies. Contains Lactobacillus acidophilus and Lactobacillus helveticus (bulgaricus). Lactinex Becton, Dickinson, and Co Available as capsules and packets. Contains Lactobacillus reuteri RC-14, Lactobacillus rhamnosus GR-1. Available as Fem-Dophilus Jarrow formulas capsules. Culturelle Digestive Amerifit Nutrition, Inc Contains L. rhamnosus GG. Each capsule contains 10 billion CFUs. Adult Formula Contains five probiotic strains: L. Acidophilus, L. Rhamnosus,L. Plantarum, B. Custom Probiotics Inc CP-1 Lactis and B. Bifidum. Each capsule has 50 billion CFUs. Contains B. longum, B. breves, B. infantis, L. plantarum, L. rhamnosus, and L. OWP probiotics One Wellness Place acidophilus. Each capsule has 15 billion CFUs. Good Belly fruit drink NextFoods Contains L. plantarum 299v. Each serving contains 20 billion CFUs.

Supplements

 Amount of active culture  Bacterial blend  Indications  Precautions  Should survive gastric acid and bile

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Probiotics tested in specific disease states

Disease Probiotic Strain Comments Number needed to treat (NNT) is 10.2 to prevent one case S. boulardi [37,38] Prevention of antibiotic associated of AAD. diarrhea (AAD) Lactobacillus rhamnosus GG (LGG) [39-41] Effective on adults and children in RCT’s. Prevention of Clostridium S. boulardii, LGG, or both [52] Study results are not statistically significant. difficile Infection (CDI) Prevention of recurrence after first CDI S. boulardii [53] Reduction of recurrence of CDI by half. Moderate evidence for improving eradication but good Lactobacillus rhamnosus GG (LGG), S. boulardii, L Helicobacter pylori eradication evidence of reduction in side effects leading to improved acidophilus [55] compliance. Ulcerative Colitis E coli Nissle 1917 [68] Promising role in maintenance of remission.

VSL#3 [70] Role in induction and maintenance of remission of UC.

Lactobacillus rhamnosus GG (LGG) [71,72], Lactobacillus Crohn’s Disease No role in induction or prolonging of remission of CD. johnsonii LA1[73]

Irritable Bowel Syndrome Bifidobacterium infantis 35624 [80], VSL#3 [81] Significant improvements in IBS symptoms.

But PROPATRIA trial showed an increased incidence of Acute Pancreatitis Lactobacillus plantarum 299 [88] infection, MODS and bowel ischemia. Bifidusbacterium spp and Prophylactic probiotics reduced NEC and mortality. Necrotizing Enterocolitis (NEC) Lactobacillus acidophilus [148] Increased infection is noted among VLBW (<750 g). Increased systemic IgA and IgG concentrations are noted Multi-Organ Dysfunction Syndrome VSL#3 [118] but MODS scores were not significantly affected by (MODS) probiotic treatment. Alone when given to mothers during pregnancy did decrease Allergy and Immune Response Lactobacillus rhamnosus GG (LGG) [125-127] the risk of atopic dermatitis but similar results were not seen when given with other probiotic strains. Number needed to treat (NNT) is 5 to prevent one case of Ventilator Associated Pneumonia (VAP) Lactobacillus rhamnosus GG (LGG) [142] VAP.

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Specific disease states where probiotics beneficial

 Acute onset of infectious diarrhea

 Antibiotic associated diarrhea

 C-dif associated diarrhea

 IBS

 IBD

 Chrohns

 Ulcerative colitis

 Complications of chronic liver disease and hepatic encephalopathy

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

Acute onset infectious diarrhea

 Mostly pediatric studies

 Prevention data modest;

 Lactobacillus rhamnosus GG (LGG), L. retueri, L. casei have shown benefit (NNT 7)

 American Academy of Peds recommends vaccine for rotovirus over use of probiotic for prevention

 Not sufficient data to support use to prevent traveler’s diarrhea

 However, use in treatment, well documented. Reduces severity and duration by 1 day

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

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Antibiotic associated diarrhea

 Well evaluated for protective effect in preventing AAD

 LGG + S. boulardii (NNT 7)

 AAP supports for prevention but not treatment

 In adults, limits duration

 Reduced incidence of c-dif associated diarrhea (L. casei, L. acidophilus)

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

Clostridium difficile associated diarrhea (CDAD)

 Current treatment: metronidazole, oral vancomycin

 S. boulardii, 500 mg bid, 4 weeks after antibiotic therapy reduced overall recurrence in those with history of CDAD, but did not reduce new incidence.

 Ongoing research inconclusive

 Likely, more to come…

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

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Irritable bowel syndrome (IBS)

 Much study variability (inclusion/exclusion of specific probiotic strains, single vs multiple dosing regimes and varied organisms)

 LGG moderately improves pain symptoms in children with IBS

 No clinical significant findings in adults, except single strain lactobacillus

 B. infantitis +/- lactobacillus improved pain, bloating

 American College of Gastroenterology and excpert consensus panels support use of probiotics for symptom reduction, with greatest benefit from bifidobacteria + lactobacillus

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

Inflammatory bowel disease (IBD)

 IBD includes Chron’s, ulcerative colitis and pouchitis.

 Pathophysiology of intestinal microbiome alteration. Defect in the innate immune response to commensual bacteria results in exaggerated adaptive immune response, which may kill certain bacteria. This process less implicated in UC and pouchitis

 Chron’s – probiotic use not supported; no conclusive data

 UC – ECN helps induce remission and maintain remission

 High dose VSL#3 – symptom improvement and less bleeding and increased remission

 Pouchitis – occurs 10-20% UC after ileal anal pouch formation surgery but improves formation after takedown

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

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In chronic liver disease/hepatic encephalitis

 Luminal microbiota play role in pathogenesis of spontaneous peritonitis and hepatic encephalopathy due to ammonia produced by gut .

 Lactulose is pre-biotic for lactobacilli, limiting bacterial ureases

 Inconclusive data thus far, but studies looking at lactobacillus acidophilus

Ciorba, Clin Gastroenterol Hepato. 2012 Sept; 10(9)

Considerations regarding use of probiotics

 Common side effect gas and bloating, but usually transient

 Different strains have unique properties for benefit of host

 One probiotic does not treat every GI illness

 Should be used in adjunct to conventional therapy, not as monotherapy

 Must be taken continuously throughout the period of desired effect

 Caution in critically ill or severely immunocompromised – insufficient data

 Separate use of antibiotics by at least 2 hours

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Future implications???

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References

 Boirivant, M., Strober, W. The mechanism of action of probiotics. Current Opinion in Gastroenterology. (20078)23.

 Ciorba, M. A gastroenterologist’s guide to probiotics. Clinical Gastroenterology and Hepatology. (2012)10(9).

 Gogineni, V., Morrow, L., Malesker, M. Probiotics: Mechanisms of action and clinical applications. Probiotics and Health. (2013)11.

 Hemarajata, P., Versalovic, J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology; (2013)6(1).

 Lakhan, S., Kirchgessner, A. Gut inflammation in chronic fatigue syndrome. Nutrition and Metabolism. (2010)7(79).

 Miller, M., Bassler, B. Quorum sensing in bacteria. Annual Reviews in Microbiology. (2001)55.

 Nenci, A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature. (2007)446.

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