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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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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

Some basics…

Nutr Metab (London). 2010; 7:79

Yeast

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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 probioticsTrade Name Manufacturer Comments

Yo-Plus yogurt Yoplait IncContains B. animalis lacis Bb-12 in addition to S. thermophilus abd L. bulgaricus per serving.

DanActiveDannon Inc

Contains S. thermophilus and L. bulgaricus in addition to L. casei DN-114 001. Each serving contains 10 billion CFUs.Cultured milk

VSL#3 packets Sigma-Tau PharmaceuticalsContains B. breve, B. infantis, B. longum, L. acidophilus, L. bulgaricus, L. casei, 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.

Philips Colon Health capsules Proctor & GambleIncludes Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1 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.

Attune nutrition bars Attune FoodsContains Koshar Lactobacillus acidophilus NCFM, L. casei Lc-11 and Bifidobacterium lactis HN019. Contains 3g fiber. Each serving contains 6.1 billion CFUs.

Align capsules Proctor & GambleContains Bifidobacterium infantis 35624 in a vegetarian capsule shell. Each capsule contains 1 billion bacteria.

Sustenex Schiff Nutrition InternationalContains Bacillus coagulans GBI-30, 6086 (BC30). Available as capsules, chewies and gummies.

Lactinex Becton, Dickinson, and CoContains Lactobacillus acidophilus and Lactobacillus helveticus (bulgaricus). Available as capsules and packets.

Fem-Dophilus Jarrow formulasContains Lactobacillus reuteri RC-14, Lactobacillus rhamnosus GR-1. Available as capsules.

Culturelle Digestive Amerifit Nutrition, Inc Contains L. rhamnosus GG. Each capsule contains 10 billion CFUs.

Adult FormulaCustom Probiotics Inc

Contains five probiotic strains: L. Acidophilus, L. Rhamnosus,L. Plantarum, B. Lactis and B. Bifidum. Each capsule has 50 billion CFUs.CP-1

OWP probiotics One Wellness PlaceContains B. longum, B. breves, B. infantis, L. plantarum, L. rhamnosus, and L. 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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Disease Probiotic Strain Comments

Prevention of antibiotic associated diarrhea (AAD)

S. boulardi [37,38]Number needed to treat (NNT) is 10.2 to prevent one case of AAD.

Lactobacillus rhamnosus GG (LGG) [39-41] Effective on adults and children in RCT’s.

Prevention of Clostridium difficile Infection (CDI)

S. boulardii, LGG, or both [52] Study results are not statistically significant.

Prevention of recurrence after first CDI S. boulardii [53] Reduction of recurrence of CDI by half.

Helicobacter pylori eradicationLactobacillus rhamnosus GG (LGG), S. boulardii, L acidophilus [55]

Moderate evidence for improving eradication but good evidence of reduction in side effects leading to improved 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.

Crohn’s DiseaseLactobacillus rhamnosus GG (LGG) [71,72], Lactobacillus johnsonii LA1[73]

No role in induction or prolonging of remission of CD.

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

Acute Pancreatitis Lactobacillus plantarum 299 [88]But PROPATRIA trial showed an increased incidence of infection, MODS and bowel ischemia.

Necrotizing Enterocolitis (NEC)Bifidusbacterium spp and Prophylactic probiotics reduced NEC and mortality.

Increased infection is noted among VLBW (<750 g).Lactobacillus acidophilus [148]

Multi-Organ Dysfunction Syndrome (MODS)

VSL#3 [118]Increased systemic IgA and IgG concentrations are noted but MODS scores were not significantly affected by probiotic treatment.

Allergy and Immune Response Lactobacillus rhamnosus GG (LGG) [125-127]Alone when given to mothers during pregnancy did decrease the risk of atopic dermatitis but similar results were not seen when given with other probiotic strains.

Ventilator Associated Pneumonia (VAP) Lactobacillus rhamnosus GG (LGG) [142]Number needed to treat (NNT) is 5 to prevent one case of VAP.

Probiotics tested in specific disease states

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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.