Tag Archives for " Probiotics "

Probiotic FAQ: Part 2

It’s finally Spring in Ohio! Trees are blooming, and it’s warm enough for walking and playing outside. Our daughter learned to ride a bike without training wheels this week and she’s been non-stop asking to go outside. Balance bikes are amazing, she literally tried the real bike for 1 day before she got it after using the balance bike the last few years.

This is the final post in my Probiotic Series at least for now! If you haven’t checked out the other post, please do, it starts with Probiotics 101, then Probiotic FAQ: Part 1 . And now on to Part 2! I also have a post over on my friend Lindsey Elmore’s site you should read as well. Thanks again to my interns Vineeta Rao and Ruth Gunti who worked on this series with me.

I hope these post help explain some of the basics about probiotics and the answer your questions, if you have further questions. Don’t hesitate to reach out.

Dr. Hartzler

If I have histamine intolerance, should I avoid certain strains? If so which ones?

Histamine intolerance is a condition in which the body has imbalanced levels of histamine. In this state, through the body’s own metabolic processes or consumption of histamine-rich foods, the body has too much histamine and may react to certain food with allergic-like symptoms such as hives, skin rashes, and other digestive symptoms.1 Gut bacteria are involved in both producing and degrading histamine, and having too many histamine-producing bacteria or too little histamine-degrading bacteria may cause elevated histamine levels.2,3 Therefore, it is crucial to select a probiotic that contributes to the proper balance of histamine in the body.

If you have histamine intolerance, it is important to avoid certain species of histamine-producing bacteria when selecting a probiotic. Those that should be avoided are Lactobacillus casei, Lactobacillus Bulgaricus, Streptococcus thermophilus, Lactobacillus delbrueckii, Lactobacillus helveticus.3
In contrast, certain probiotics appear to aid in relieving the imbalances found with histamine intolerance. Lactobacillus rhamnosus strains GG and c705 have been observed to inhibit the effect of histamine in the body.4 Additionally, in vitro studies suggest that bifidobacterium lactis and lactobacillus plantarum species promote histamine breakdown. 5,6

Should I take a probiotic while also taking an antibiotic? If so which one, and for how long?

Although clinicians have generally supported using probiotics with an antibiotic course, this is an area of controversy as new studies suggest that probiotics may interrupt the body’s natural process of restoring the bacterial balance in the gut. There are many studies that support using probiotics to prevent antibiotic-associated diarrhea, and among the tested species S. boulardii has specifically been shown to be effective.7 Studies have also shown that Lactobacillus rhamnosus GG, the strain contained in the Culturelle probiotic, appears and effective to prevent antibiotic associated diarrhea (AAD) in an outpatient setting.8 The recommended  dose is 107 to 1010 colony-forming units (CFU) per capsule (taken one to 3 times daily) as that is what has been studied; duration of therapy can be 1-3 weeks or the entire length of time that the patient is on antibiotics.9 For reference, Metagenics “UltraFlora LGG” and Culturelle “Digestive Health” products contains 1010 CFU per dose, and Culturelle “Kids” product contains 109 CFU per dose, making these products good choices for AAD.10 It is generally recommended to take probiotics for a couple months after therapy and consuming fermented foods. Overall it is said that “probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics.” 8-10

However, there is emerging research that suggests that probiotics may actually delay spontaneous recovery of the microorganisms in the gut, or the “gut microbiome.” A recent study compared spontaneous gut recovery to probiotic use in humans receiving a broad-spectrum antibiotic course. By performing endoscopies and examining the stool from the patients before and after receiving antibiotics, normal genetic expression of bacteria in the gut was delayed by up to 5 months in the probiotic group versus a matter of weeks in the group allowed to spontaneously recover.11,12 The in vitro portion of the study suggested that Lactobacillus acidophilus may inhibit the native gut microbiome.11 While this study cautions against the preventative use of probiotics with an antibiotic course, further studies to shed light on the benefit or harm of probiotics are needed to come to a clear conclusion.12

In the meantime, it may be wise to avoid probiotics with Lactobacillus acidophilus when taking an antibiotic course. One of the challenges as a provider recommending probiotics is that this was just 1-2 studies in the midst of all the literature and didn’t not look at saccharomyces boulardii and its effect, therefore it really just raises questions for future research and gives us a pause to our practice of using blanket probiotics for everyone on antibiotics habit.

If I have dysbiosis or Small intestinal bacterial Overgrowth, should I avoid pre-biotics or certain probiotic strains?

Small Intestinal Bacterial Overgrowth (SIBO) typically refers to a form of dysbiosis (imbalance of bacteria on the body) attributed to an excessive overgrowth or changes in types of bacteria in the small-intestine.13,,14 While the small intestine is not sterile, it has far fewer bacteria than the large intestine. Thus, SIBO may result from the specific bacteria that normally grows in the large intestine growing inappropriately in the small intestine.13,14 Other causes of SIBO include multiple courses of antibiotics and impaired defense mechanisms such as low stomach acid, which may be caused by use of Proton Pump Inhibitors (PPIs). While the definition is constantly changing and expanding to include other forms of dysbiosis, SIBO is typically characterized by non-specific gastrointestinal symptoms such as bloating, abdominal discomfort, diarrhea, fatigue, and weakness and might be treated with an antibiotic course.13,14

There are several studies that actually support the use of probiotics for this disorder.15  However, at the moment there is little consensus across the studies as to which probiotics species and strains will provide benefit for SIBO. Regardless of the species, the theoretical concern with using probiotics in SIBO even if the bacteria added to the gut is “good” bacteria, too much bacteria often produces symptoms of bloating and gas, which would worsen symptoms. In SIBO, patients often have an overgrowth of D-lactate-producing bacteria, so it may be best to avoid probiotics that also produce D-lactate such as Lactobacillus acidophilus.16

In the past it has also been generally recommended that one avoid the use of prebiotics until SIBO symptoms under control. Currently, studies that challenge this notion are frequently emerging, and in time, we may see a demonstrable benefit of certain probiotics and prebiotics in SIBO.16 However, until studies show which species and strains relieve rather than aggravate SIBO symptoms, it is likely best to avoid prebiotics and probiotics that produce D-lactate. In general, I recommend treating the overgrowth before working on replacing the flora with probiotics. Once those probiotics are tolerated, consider adding prebiotics to support healthy growth of gut flora along with other measures to prevent SIBO recurrence. Specifically, Partially Hydrolyzed Guar Gum (PHGG) is a prebiotic that has been shown to treat SIBO when administered alongside the antibiotic rifaximin better than rifaximin alone.17 Thus, this product could be a good option for encouraging healthy gut flora growth.

That’s a wrap. As always you can find great probiotic options on my FullScript Store or at YoungLiving. Feel free to message me if you have specific questions. We have so much science but we are still not quite a place were we absolutely know which probiotic product is going to work for each person. We are moving closer to that each day.

References:

  1. Maintz L,  Novak N.Histamine and histamine intolerance.Am J Clin Nutr. 2007;85(5):1185-96.
  2. Pugin B, Barcik W, Westermann P, et al. A wide diversity of bacteria from the human gut produces and degrades biogenic amines. Microb Ecol Health Dis. 2017;28(1):1353881.
  3. What causes Histamine Intolerance. Facts vs Fitness. https://factvsfitness.com/probiotics-histamine-intolerance/. Updated July 27, 2017. Accessed January 23, 2019.
  4. Oksaharju A, Kankainen M, Kekkonen RA, et al. Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cells. World J Gastroenterol. 2011;17(6):750-9.
  5. Mokhtar S., Mostafa G, Taha R. et al. Effect of different starter cultures on the biogenic amines production as a critical control point in fresh fermented sausages. Eur Food Res Technol. 2012;235(3): 527-535.
  6. Capozzi V, Russo P, Ladero V, et al. Biogenic Amines Degradation by Lactobacillus plantarum: Toward a Potential Application in Wine. Front Microbiol. 2012; 3: 122.
  7. Mcfarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202-22.
  8. Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the Prevention of
    Antibiotic-Associated Diarrhea in Outpatients-A Systematic Review and Meta-Analysis. Antibiotics (Basel). 2017 Oct 12;6(4).
  9. Rodgers B, Kirley K, Mounsey A. PURLs: prescribing an antibiotic? Pair it with probiotics. J Fam Pract. 2013;62(3):148-50.
  10. Antibiotic Use & Associated Diarrhoea Prevention. Probiotic Advisor. https://www.probioticadvisor.com/ Accessed February 9, 2019.
  11. Suez J, Zmora N, Zilberman-Schapira G, et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018;174(6):1406-1423.
  12. Kresser C. RHR: What the Latest Research Says about Probiotics, with Lucy Mailing. https://chriskresser.com/what-the-latest-research-says-about-probiotics-with-lucy-mailing/ Updated November 4, 2018. Accessed February 9, 2019.
  13. Drake LE, Guilliams TG. Small intestinal bacterial overgrowth (SIBO): diagnostic challenges and functional solutions. Point Institute. 2018;14(2)1-15.
  14. Kresser C. What Causes SIBO (Small Intestinal Bacterial Overgrowth) and Why It’s So Hard To Treat. https://chriskresser.com/sibo-what-causes-it-and-why-its-so-hard-to-treat/ Updated November 4, 2014. Accessed February 9, 2019.
  15. Chen WC, Quigley EM. Probiotics, prebiotics & synbiotics in small intestinal bacterial overgrowth: opening up a new therapeutic horizon!. Indian J Med Res. 2014;140(5):582-4.
  16. Kresser C. RHR: Treating SIBO, Cold Thermogenesis, and When to Take Probiotics. https://chriskresser.com/treating-sibo-cold-thermogenisis-and-when-to-take-probiotics/. Updated March 12, 2013. Accessed February 9, 2019.
  17. Furnari M, Parodi A, Gemignani L, et al. Clinical trial: the combination
    of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacy Ther. 2010;32(8):1000-6.



1 Probiotic FAQ: Part 1

Hope you all had a great weekend! Our family was visiting my husband’s parents. On Friday my daughter and I had appointments for acupressure allergy treatments which went very well. I’ve been struggling with a lot of sinus headaches recently and I’m hopefully that these will help those calm down. One of the foods I was reacting to was chocolate 😔, but thankfully the treatment should allow me to put it back in my diet occasionally. 😊 I think I’m going to try to abstain for a little while before re-introducing. Our daughter is doing so well from where she was as a baby, hopefully these will help her be able to continue to expand her food choices. We had a lot of success with them in the past and calming down her eczema.

We enjoyed a relaxing Saturday with his family and today are celebrating his mom’s birthday before we head home. Hopefully this week we also get to meet our newest nephew who is due to arrive any day now!

Probiotics are a hot topic, and I don’t have all the answers but this post and my post next week will help address some of the most common questions I receive about them. We aren’t at a place yet where we can say you have this issue and you need this particular product 100%, but we have good data and is helping us guide recommendations. The microbiome is complex and everyone’s is different which makes it challenging. A lot of probiotic treatment is trial and error but sometimes what we try the first few times works! If you missed the first post Probiotic 101, make sure to check it out. As with the last post, two of my interns Vineeta Rao and Ruth Gunti worked hard on this! Thank you!

Hope you enjoy this first FAQ and stay tuned for more next week.

Dr. Hartzler

If I have a milk or other food allergy, can I take probiotics?

Yes. A  randomized controlled-trial found that supplementation with a probiotic helped infants allergic to cow’s milk develop a tolerance at a higher rate.1  Severe milk allergy patients should avoid probiotics made from milk. Dairy free probiotics are recommended for those with severe intolerance or allergy, where as dairy free would not be necessary for lactose intolerant patients. Additionally, a recent study that followed peanut allergic children found that a combination of probiotics (Lactobacillus rhamnosus) and peanut oral immunotherapy produced a sustained non-allergic response in children even four years after initial treatment indicating potential future use of probiotics in immunotherapy for the treatment of food allergies.2

If I have lactose intolerance, can I take probiotics?

Yes. In fact, probiotics are being used to help those with lactose intolerance. In a review article examining the relationship between probiotics and their use in those with lactose intolerance it was found that there was an overall positive relationship. The species of bacteria that were most common among the reviews studied were lactobacillus acidophilus, lactobacillus bulgaricus, and streptococcus thermophilus all of which demonstrated some level activity. 3

The World Gastroenterology Organisation Global Guidelines on probiotics states that “Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus improve lactose digestion and reduce symptoms related to lactose intolerance.”3

Should I take my probiotic with or without food?

A study looking at four species of bacteria found that survival through the GI tract was most preserved when given with a meal or 30 minutes before the meal.4   This may be due to the changes in acidity of the stomach during the fed and fasting states. During the fasting state, the stomach environment is more acidic, making it is more difficult for the bacteria to survive. Upon eating, however, the stomach environment becomes less acidic, thus providing a more favorable environment for bacteria to thrive. 4,5 In this study, probiotic survival was greater when taken with foods high fat content than with carbohydrates, apple juice, or water alone. Fat content appears to help “coat” the bacteria to protect against stomach acid. Thus, it is best to take your probiotic with a higher fat meal or snack to help the bacteria survive transit through the acidic stomach environment.4

What is the safety profile of probiotics?

Studies have found that probiotics have minimal to no side effects. Side effects that are observed are most commonly bloating and flatulence, but the symptoms are mild and subside with continued use of the probiotic. Constipation and increased thirst have also been rarely associated with the species S. boulardii.6 The extreme side effects that have been found are in patients whose immune system have already been compromised.

Why might my probiotic cause diarrhea or constipation?

Diarrhea or constipation can occur with probiotics especially at the start of therapy due to multiple factors. Likely, it depends on the degree to which the gut is imbalanced to begin with, and as the gut is being rebalanced, bacteria can release by-products through fermentation that influence how fast the bowels move. Also, since the brain and gut appear to influence each other, lifestyle factors such as stress may influence the gut’s movement. While we do not know how each of these factors specifically affect the gut, there are multiple neurological influences by different types of bacteria which may contribute to the speed in which transit happens.7

That is a wrap for today’s FAQ.. more to come next week! Next week I will address probiotics with antibiotics, histamine intolerance, and Small Intestinal Bacterial Overgrowth (SIBO). Don’t miss it! If you are looking for a quality probiotic feel free to check out my FullScript Store or send me an email if you need help!

References:

  1. Probiotic formula reverses cow’s milk allergies by changing gut bacteria of infants. The University of Chicago Medicine. https://www.uchicagomedicine.org/biological-sciences-articles/probiotic-formula-reverses-cows-milk-allergies-by-changing-gut-bacteria-of-infants. Updated September 22, 2015. Accessed February 9, 2019.
  2. Hsiao KC, Ponsonby AL, Axelrad C, Pitkin S, Tang MLK. Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial. Lancet Child Adolesc Health. 2017;1(2):97-105.
  3. Oak SJ, Jha R. The effects of probiotics in lactose intolerance: A systematic review. Crit Rev Food Sci Nutr. 2018;9:1-9.
  4. Tompkins TA, Mainville I, Arcand Y. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011;2(4):295-303.
  5. Zembroski R. Why taking probiotics on an empty stomach is a bad idea. REBUILD. https://www.drzembroski.com/why-taking-probiotics-on-an-empty-stomach-is-a-bad-idea/. Accessed February 9, 2019.
  6. Williams NT. Probiotics. Am J Health Syst Pharm. 2010;67(6):449-58.
  7. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17-44.

3 Probiotics 101

It’s been a whirlwind the last few months. I’m teaching my last lecture in Endocrine tomorrow.. I’m excited it’s on functional medicine approach to pre-diabetes and obesity! The best part about teaching part-time is getting to teach what I’m passionate about. After this, I just have lots of grading and course coordination items. But the course ends next week then I’m off to Seattle, WA to speak on diabetes cardiovascular outcomes trials. It’s the same presentation from December in Anaheim showcased at a different meeting. It’s nice when you spend a lot of time on something, to be able to do it twice! For this blog post, I had a lot of help from two students working on this probiotic series, so thank you to Vineeta Rao and Ruth Gunti for your hard work. Soon they will be my colleagues! Enjoy!

Dr. Hartzler


Welcome to probiotics 101, a guide to all your FAQs!

What are probiotics?

‘Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host.’ 1 The microorganisms are bacteria of different strains that process our food into nutrients that benefit our health. Probiotics come from the Latin preposition pro (“for”) and the Greek adjective (biōtikos) meaning “fit for life, lively.” Put together this means that probiotics are for life.

Why use probiotics?

Using probiotics enhances the gut microbiota to better do its job.  The gut microbiota/microbiome is the conglomerate of bacteria that live in your gut and work together to bolster the immune system, to fight against potential infections, and to make nutrients such as vitamins, fats and other molecules that are needed by the body to function. 1  Furthermore facets of our modern day western lifestyle, such as diet, stress, geography, as well as sleep and travel patterns can negatively affect our gut microbiome meaning we don’t have a healthy gut to begin with. 2 In addition to the poor lifestyle factors, the increasingly prevalent use proton pump inhibitors is correlated with and probably contributes to “decreased bacterial richness” of  gut microbiome, an increased amount of oral bacteria that is potentially pathogenic present in the gut, and an overall greater “microbial alterations” in the gut than those on antibiotics. 3

How do probiotics work?

While probiotics are most commonly associated with replacing flora or colonizing the gut, modifications made to the gut microbiota are not likely permanent and reflect only one of many actions that probiotics have in the body. Among these actions are immune modulation, anti-inflammatory activity, pathogen antagonism, production of short chain fatty acids, repairing and strengthening of the intestinal barrier, metabolism of gut cholesterol, and enhanced antibody secretion.4 While not all probiotics encompass all of these features, depending on the strain, a given probiotic may provide one or several of these protective benefits.5

What is genus, species, and strain?

Bacteria are usually classified to the public by three names much like people who have first, middle and last names. Therefore the first name is a broad name termed genus, followed by a more specific name called a species finally followed by a strain number that is further specifies the exact kind of bacteria.  A labeled example is below!

What is the evidence for probiotic use?

Numerous review studies indicate that probiotics are beneficial overall, especially for gut health.6 However, evidence for treating or preventing specific conditions through probiotics is best established through clinical trials that demonstrate how probiotics produce a specific effect. While the number of controlled trials demonstrating specific effects in humans is still growing, probiotics have also been evaluated in animal experiments and or other in vitro studies that demonstrate efficacy and safety in terms of their use. 1  Fermented foods with probiotics in them have been consumed for centuries for health benefits. Additionally, the modern diet lacks prebiotic fiber that contributes to a diverse gut microbiome.7

What is the difference between Bifidobacterium and Lactobacillus genus of bacteria?

Lactobacillus bacteria is a type of bacteria that produces lactic acid as an end-product of its metabolism. Bifidobacterium bacteria on the other hand produce lactic acid and acetic acid; both these substances are important for the maintenance of the gut microbiome. 8,9

Here are some of the bacteria in each genus considered to be probiotics.8

Microorganisms
 considered as probiotics
Lactobacillus speciesBifidobacterium species
L. acidophilus
L. casei
L. crispatus
L. gallinarum
 L. gasseri
L. johnsonii
L. paracasei
L. plantarum
L. reuteri
L. rhamnosus
B. adolescentis
B. animalis
B. bifidum
B. breve
B. infantis
B. lactis
 B. longum

How to know you are getting a good product?

There are many overarching reviews that conclude that probiotics as a whole class are effective, suggesting that many strains share the similar levels of effectiveness. Additionally, there are number of factors that contribute to how probiotics act in our bodies such as genetics, diet and host microbiome that makes it difficult to isolate the effects of one strain over another. However, it is important that the product contains the live bacteria in large doses that will survive the harsh environments of the stomach.6

How much does the specific strain matter when ensuring that you have a good product? As more studies for probiotic use emerge, there is an ongoing controversy about the importance of the strain. On one side of the debate, larger studies that examine multiple clinical trials suggest that probiotics have benefit even when grouping similar strains together in one class. The theory behind this position is that similar strains of probiotics will have actions causing similar effects in the body.6 One the other side of the debate, some clinicians compare strain selection to choosing a particular antibiotic to attack a specific disease-causing microbe.4 Advocates of this position point to the fact that Lactobacillus plantarum DSM 9843 reduces irritable bowel syndrome while Lactobacillus plantarum MF 1298 aggravates the condition and thus conclude that when supporting a specific condition, one should only use a strain that has demonstrated efficacy for that specific condition.10-12

In summary, data for use of probiotics is exploding on a daily basis. Probiotics are useful to promote healthy gut transit and repair and for a myriad of immune benefits.  In addition, data suggests significant changes to the gut microbiome is most easily stimulated by ingestion of prebiotics, which are non-digestible foods that promote and stimulate the growth of bacteria in the gut.13 Prebiotics are often combined with probiotic supplements.  Sometimes they may not be well tolerated by certain individuals especially those that have an imbalance in bacteria. Certain non-gas producing prebiotics may be helpful for some patients. We will talk more about these situations in my next post!

If you are looking for quality probiotics. Please check out my Fullscript store and click on the probiotics category! I’m happy to help with simple questions on products via email or if you are interested in a 1:1 personal GI health consults with my team, please let me know. We are launching tele-health services soon!

SOURCES:

  1. Fijan S. Microorganisms with claimed probiotic properties: an overview of recent literature. Int J Environ Res Public Health. 2014;11(5):4745-67.
  2. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17-44.
  3. Imhann F, Bonder MJ, Vich vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65(5):740-8.
  4. Probiotic Advisor. The Importance of Strain. https://www.probioticadvisor.com/probiotic-essentials-1/the-importance-of-strain/#.XC-EEPZFxPZ. Accessed January 21, 2019.
  5. Hill, C., et al., Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol, 2014. 11(8): p. 506-514.
  6. California Dairy Research Foundation. Is it time to consider generic probiotic effects? http://cdrf.org/2013/03/01/is-it-time-to-consider-generic-probiotic-effects/. Updated March 1, 2013. Accessed August 20, 2018.
  7. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8(2):172-184.
  8. Kechagia M, Basoulis D, Konstantopoulou S, et al. Health benefits of probiotics: a review. ISRN Nutr. 2013;2013:481651.
  9. Bifidobacteria Institute. Difference between bifidobacteria and lactobacillus. http://bb536.jp/english/basic/basic03.html. Accessed August 20, 2018.
  10. Ducrotte, P., P. Sawant, and V. Jayanthi, Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol, 2012. 18(30): p. 4012-8.
  11. Niedzielin, K., H. Kordecki, and B. Birkenfeld, A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol, 2001. 13: p. 1143-1147.
  12. Ligaarden, S.C., et al., A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial. BMC Gastroenterol, 2010. 10: p. 16.
  13. Cashman K. Prebiotics and calcium bioavailability. Curr Issues Intest
    Microbiol. 2003 Mar;4(1):21-32. Review.

Eczema & Probiotics

The majority of this post was written by Dr. Taylor Edwards, who was a medical student that rotated with me earlier this year, now she is a Doctor of Osteopathic Medicine off to residency!  I take medical students from Ohio University and work with the pharmacists in my area to expose them to different areas of pharmacy practice. I also talk to them a lot about functional medicine and depending on the speciality they are interested in, we look at what they could study that will impact how they treat patients in the future.  Dr. Edwards. is training to be a dermatologist so of course we talked about gut health and it’s relationship to atopic conditions such as eczema. I hope you enjoy her post!

Dr. Hartzler

 

Eczema, also called atopic dermatitis, is a common, chronic and relapsing skin condition characterized by extreme itching. Currently, the incidence of eczema in industrialized nations is 20%, representing a 2-3 fold increase in recent decades.1,2 The reason for this increase remains unclear due to the complex etiology of the disease. However, it is reasonable to assume that this increase cannot be explained by genetic factors alone. Research has demonstrated that food allergy, defects in the gut mucosal barrier (ie leaky gut), and increased intestinal permeability may play a role in the development of eczema.3 Dietary manipulation remains a controversial topic in the treatment of atopic diseases, however, some studies show promise for the use of probiotics in the treatment and prevention of atopic dermatitis in young children.4

Probiotics are normal, healthy bacteria of the human gut that can be consumed in food or as dietary supplements.5 Lactobacilli and bifidobacteria are the most studied types of probiotics and are thought to assist the neonatal immune system in creating T-regulatory immune cells that are vital in preventing atopic disease.3,6-8 One large study supports the use of probiotics as preventative care due to findings that the incidence of eczema was 20% lower in infants and children that were exposed to probiotics early in life or during gestation.9

Another study demonstrated that probiotics may represent a helpful adjuvant therapy in the treatment of eczema. Forty young children between the ages of 3 months and 6 years with a diagnosis of eczema were divided equally into two groups and treated with probiotics (a mixture of 7 strains including Lactobacilli and bifidobacteria gena) or placebo. At the end of 8 weeks, the children that were treated with the probiotic mixture demonstrated a significant reduction in the severity of their eczema.10 While not all studies regarding probiotics as a modality to improve eczema have demonstrated consistent results, one large meta-analysis that evaluated data from ten studies and 678 patients found that when compared to placebo, probiotics may play a role in reducing the severity of eczema.11

Along with probiotics, cow’s milk is another area of interest for eczema researchers. Many parents believe the development of eczema in their child was temporally associated with the introduction of cow’s milk or cow’s milk based formula. Nearly 100 studies have examined the influence of hydrolyzed formulas versus cow’s milk based formulas in the development of eczema.  The most well-known study, the GINI study, found that infants given exclusively hydrolyzed formula were 50% less likely to develop eczema compared to infants who were fed cow’s milk based formula (hydrolyzed formula did not show benefit over breast milk).12-16 Soy based formula is often believed to be less allergenic than cow’s milk based formula, however, research does not support this claims.17

Exclusion diets have also been studied in individuals with eczema with less promising results. However, children with eczema and suspected egg allergy may benefit from a diet excluding eggs.18 In situations where special diets are attempted, it is recommended to adhere to the diet for a limited time of 4-8 weeks and then return to a normal diet to assess the efficacy of dietary interventions.4

So the PharmToTable Rx for eczema definitely includes quality probiotics (find them in my fullscript store!) and addressing gut health! My favorite quality probiotics include those by OrthoMolecular, Metagenics, Klaire Labs, and Young Living. For kids omega-3’s and vitamin D are certainly another good idea to reduce inflammation and support gut healing. For breastfed babies, elimination diets for mom are also important if you can figure out the trigger. For formula fed babies, a hydrolyzed formula is a good place to start, but possibly further reducing allergens by moving to a corn-free and hydrolyzed option like Alimentum Ready Feed may be necessary. You definitely have to give it at least a month if not two months to see the full effect.

Also check out this post by the National Eczema Association as well for further reading on this topic! There is also some interested new thoughts and emerging evidence about using probiotics topically to help heal the skin. This article discusses the topic.

References: 

  1. Thestrup-Pedersen K. Treatment principles of atopic dermatitis. J Eur Acad Dermatol Venereol. 2002;16(1):1-9. http://www.ncbi.nlm.nih.gov/pubmed/11952283. Accessed February 11, 2018.
  2. Eichenfield LF, Hanifin JM, Beck LA, et al. Atopic Dermatitis and Asthma: Parallels in the Evolution of Treatment. Pediatrics. 2003;111(3):608-616. doi:10.1542/peds.111.3.608.
  3. Isolauri E. Intestinal involvement in atopic disease. J R Soc Med. 1997;90 Suppl 30:15-20. http://www.ncbi.nlm.nih.gov/pubmed/9176124. Accessed February 11, 2018.
  4. Finch J, Munhutu MN, Whitaker-Worth DL. Atopic dermatitis and nutrition. Clin Dermatol. 2010;28(6):605-614. doi:10.1016/j.clindermatol.2010.03.032.
  5. Salminen S, Bouley C, Boutron-Ruault MC, et al. Functional food science and gastrointestinal physiology and function. Br J Nutr. 1998;80 Suppl 1:S147-71. http://www.ncbi.nlm.nih.gov/pubmed/9849357. Accessed February 11, 2018.
  6. Smits HH, Engering A, van der Kleij D, et al. Selective probiotic bacteria induce IL-10–producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin. J Allergy Clin Immunol. 2005;115(6):1260-1267. doi:10.1016/J.JACI.2005.03.036.
  7. Prescott SL, Björkstén B. Probiotics for the prevention or treatment of allergic diseases. J Allergy Clin Immunol. 2007;120(2):255-262. doi:10.1016/J.JACI.2007.04.027.
  8. Pessi T, Sütas Y, Hurme M, Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000;30(12):1804-1808. http://www.ncbi.nlm.nih.gov/pubmed/11122221. Accessed February 11, 2018.
  9. Pelucchi C, Chatenoud L, Turati F, et al. Probiotics Supplementation During Pregnancy or Infancy for the Prevention of Atopic Dermatitis. Epidemiology. 2012;23(3):402-414. doi:10.1097/EDE.0b013e31824d5da2.
  10.   Farid R, Ahanchian H, Jabbari F, Moghiman T. Effect of a new synbiotic mixture on atopic dermatitis in children: a randomized-controlled trial. Iran J Pediatr. 2011;21(2):225-230. http://www.ncbi.nlm.nih.gov/pubmed/23056792. Accessed February 11, 2018.
  11.   Michail SK, Stolfi A, Johnson T, Onady GM. Efficacy of probiotics in the treatment of pediatric atopic dermatitis: a meta-analysis of randomized controlled trials. Ann Allergy, Asthma Immunol. 2008;101(5):508-516. doi:10.1016/S1081-1206(10)60290-6.
  12.   Laubereau B, Brockow I, Zirngibl A, et al. Effect of breast-feeding on the development of atopic dermatitis during the first 3 years of life—results from the GINI-birth cohort study. J Pediatr. 2004;144(5):602-607. doi:10.1016/J.JPEDS.2003.12.029.
  13.   Banks JR. THE EFFECT OF HYDROLYZED COW’S MILK FORMULA FOR ALLERGY PREVENTION IN THE FIRST YEAR OF LIFE: THE GERMAN INFANT NUTRITIONAL INTERVENTION STUDY, A RANDOMIZED, DOUBLE-BLIND TRIAL. Pediatrics. 2004;114(2):521-522. doi:10.1542/peds.114.2.S1.521-b.
  14.   Oldaeus G, Anjou K, Björkstén B, Moran JR, Kjellman NI. Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Arch Dis Child. 1997;77(1):4-10. http://www.ncbi.nlm.nih.gov/pubmed/9279143. Accessed February 11, 2018.
  15.   Halken S, Hansen KS, Jacobsen HP, et al. Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: a prospective, randomized study. Pediatr Allergy Immunol. 2000;11(3):149-161. http://www.ncbi.nlm.nih.gov/pubmed/10981524. Accessed February 11, 2018.
  16.   Nentwich I, Michková E, Nevoral J, Urbanek R, Szépfalusi Z. Cow’s milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula. Allergy. 2001;56(12):1144-1156. http://www.ncbi.nlm.nih.gov/pubmed/11736743. Accessed February 11, 2018.
  17.   Osborn DA, Sinn JK. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database Syst Rev. October 2006. doi:10.1002/14651858.CD003741.pub4.
  18.   Lever R, MacDonald C, Waugh P, Aitchison T. Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs. Pediatr Allergy Immunol. 1998;9(1):13-19. http://www.ncbi.nlm.nih.gov/pubmed/9560837. Accessed February 11, 2018.

 

Allergic Rhinitis & The Gut..Is it time for Probiotics?

Despite summer being in full swing here in Ohio, there are a lot of people here and across the country are who are still suffering from seasonal allergies and what the medical community refers to as allergic rhinitis (AR). AR is one of the most common diseases that effects nearly 1 in every 6 Americans. AR is an inflammatory condition often leading to symptoms such as congestion, runny nose, sneezing, nasal itching, and watery/itching eyes.

Some experience seasonal allergies that are temporary due to triggers being pollens that come and go depending on the season. Others experience year-round or perennial allergies due to dust mites and continued triggers. Some patients could experience what is referred to as episodic allergies from triggers they encounter outside of their typical environment such as family members’ pets.1

Guidelines recommend avoiding allergic triggers as a first step in treatment such as removal of pets, using air filtration systems, and bed covers (to avoid dust mites). 1 Nasal saline rinses can be very helpful to clear out the pollens from the nasal passage before sleeping, this is my favorite one that is easy to use! Washing your hair before sleeping can also help reduce the pollens that attach to our hair follicles. From a western medicine standpoint, during serious allergy flare ups, I need to use a topical nasal steroid such as fluticasone. 1 The great part is they are now available over the counter. This can help calm down the inflammation short term as you consider other ways to address allergies more naturally. Budesonide  is the nasal steroid of choice for pregnant women, using the lowest effective dose and duration is recommended.2,3

An interesting discussion recently has been the connection between the gut and the lack of diverse healthy microbes to the development of allergies. Multiple studies indicate that the increased incidence of autoimmune and allergic diseases in developed countries may be associated with reduced diversity in bacteria exposure and changes of bacteria in various body tissue. AR and atopic eczema have been shown to be related to changes in gut microbial composition.4

“Leaky gut” is a term for an impaired intestinal barrier or an increase in gut permeability, which may also play a role in the development of asthma and allergies. The intestine should play a role as the gatekeeper of immunity and when this is broken the body can start to have a reaction to typical proteins called antigens it would not normally react to. This can include food reactions, or reactions in the nasal passageways or lungs. AR is considered by some to be an early form of an autoimmune disease.4

Thus an important part of treating seasonal allergies is making sure the gut is healthy, this is a whole post in itself that will be coming soon, but for now starting with a high quality probiotic and avoiding allergic triggers including foods that further trigger allergy symptoms is a start. For me I have a reaction to ragweed in the fall and I have found that sunflower seeds trigger my allergic rhinitis because they are similar plants. Paying attention to food triggers can be very helpful! In regards to probiotics, Vliagoftis et al performed a meta-analysis of 16 clinical trials on the treatment of AR and Asthma and found that 9 of 12 studies that elevated clinical outcomes of AR showed improvement due to the use of probiotics. They determined that probiotics may have a beneficial effect by reducing symptom severity and medication use. Most of these studies reported used some form of Lactobacillus species such as Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, some included a combination with Bifidobacterium strains.5

My favorite probiotic for adults right now is OrthoBiotic from OrthoMolecular. This is a high quality mix of the strains discussed above.  It also includes Saccharomyces boulardii which is a beneficial non-pathogenic yeast that works to balance intestinal flora.  The only patients who should not take Saccharomyces would be those with compromised immune systems. Each OrthoBiotic capsule provides seven proven probiotic strains chosen for their ability to withstand the harsh gastrointestinal (GI) environment and adhere to the intestinal tract. The specific strains found in this product have be shown to increase Secretory IgA which provides enhanced gut Immunity.

Bifidobacterium lactis (B. lactis), one of the probiotics in the above formula, is predominantly found in the colon. A double-blind, randomized placebo-controlled trial on subjects receiving B. lactis or placebo for eight weeks found that B. lactis supported a balanced immune response in individuals hypersensitive to environmental allergens.Flora Boost can be a great option for toddlers and kiddos that don’t swallow pills yet.

Ther-Biotic Complete is another great probiotic I recommend by Klaire Labs. They also have a Women’s Formula as well that supports healthy colonization in the vaginal tract as well as provides the probiotic strains above shown to be beneficial in allergic conditions. Klaire Labs formulas do need to be refrigerated upon arrival.

You can find all of these high quality probiotics in my Supplement Store on FullScript. If you have questions, feel free to reach out! Don’t forget to contact me & sign up for blog updates if you want 15% off your first order.

Stayed tuned for my next post which will discuss my favorite supplements (Quercetin, Stinging Nettles) and nutrients (Vitamin C, Bromelain, N-Acetyl-L-Cysteine) and their useful role in supporting allergic conditions. And if you need recommendations for probiotics for babies, head over to this post.

 

References:

  1. Seidman et al. Clinical Practice Guideline: Allergic Rhinitis. Otolaryngology–Head and Neck Surgery 2015, Vol. 152(1S) S1–S43.
  2. Wallace DV, Dykewicz MS, Bernstein DI, et al, “The Diagnosis and Management of Rhinitis: An Updated Practice Parameter,”J Allergy Clin Immunol, 2008, 122(2 Suppl):1-84.[PubMed 18662584]
  3. NAEPP Working Group Report on “Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment,” National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 05-5236, March 2005. Available athttp://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg/astpreg_full.pdf
  4. Hormannsperger G, et al. Gut matters: Microbe-host interactions in allergic diseases. J Allergy Clin Immunol 2012;129:1452-9.
  5. Vliagoftis et al. Probiotics for the treatment of allergic rhinitis and asthma: systematic review of randomized controlled trials. Ann Allergy Asthma Immunol. 2008;101:570–579
  6. Singh A, Hacini-Rachinel F, Gosoniu ML, Bourdeau T, Holvoet S, Doucet-Ladeveze R, Beaumont M, Mercenier A, Nutten S. Immune-modulatory effect of probiotic Bifidobacterium lactis NCC2818 in individuals suffering from seasonal allergic rhinitis to grass pollen: an exploratory, randomized, placebo-controlled clinical trial. Eur J Clin Nut. 2013 Feb;67(2):161-7.

5 Babies and Probiotics

Over recent years the connection between the gut microbiome (the bacteria in our gut, also know as our gut flora!) and chronic diseases has been stronger than ever.  There are a large number of publications linking less diverse flora to a myriad of conditions especially those in the asthma, allergy, and autoimmune realm.

The bacteria in our gut play several roles including:1

  • Critical role in regulation of the immune system
  • Provide protection against pathogen (bad bugs!) overgrowth
  • Influence host-cell growth and blood vessel growth
  • Regulate intestinal endocrine functions, neurologic signaling, and bone density
  • Provide a source of energy (5 to 10% of daily host energy requirements);
  • Biosynthesize vitamins, neurotransmitters, and multiple other compounds
  • Metabolize bile salts
  • React to or modify specific drugs
  • Eliminate exogenous toxins

Currently researchers are even studying how to implant drug peptides into the bacteria in our gut for certain conditions. One particularly interesting one is for the treatment of inflammatory Bowel disease, which often severe cases come with injectable agents that weaken the immune system all over. Wouldn’t it be great if we had targeted therapy just in the gut!

So the question is if our gut is so important, how do we help our children start out on the right track with solid gut flora.  The answer….you guessed it..probiotics!  Probiotics are “Live microbes that confer health benefits when administered in adequate amounts in the host.”1The key with infants though is to get them probiotics early in the first few days when their gut is designed to multiply those good bugs! The in utero environment was once considered sterile. However recently, DNA studies of the micro biome have found bacterial species in the placentas of healthy mothers, in amniotic fluid of preterm infants, and in meconium.1

Ideally babies born vaginally shouldn’t need this right, they swallow fluid during delivery through the vaginal canal that should seed their gut? While that is true, most of us Mommas have taken antibiotics in our lifetime, if not multiple courses, been under stress (which has been proven to change gut flora!)2, and often times are eating or have eaten a diet previously that was not friendly towards growing and multiplying good bacteria.  We also live in an environment where traces of antibiotics are in our water supply and food chain. So I recommend every baby whether born vaginally or c-section get probiotics during the first week of life. I also recommend Mommas take probiotics throughout their pregnancy.

Another way to help the flora grow is with breastmilk. Studies3,4 have shown that the guts of breast fed babies vs formula fed babies are different compositions of bacteria. Breastfed babies have more beneficial bifidobacteriam species.  Exclusive and partial formula-feeding have been shown to alter the gut bacteria toward adult patterns, increase pro-inflammatory bacterial species, increase gut permeability (leaky gut) and result in lower concentrations of fecal short-chain fatty acids compared with exclusive breastfeeding.4 While I realize this isn’t possible for every women, from my experience it’s hard, especially during those first few months.  Believe me lots of tears were shed in the process of making it work for us with my first child. Then of course pumping if you are working out of the home is hard too. But I promise it’s worth the attempt at least. The IGG in the breastmilk also helps seal the gut lining which makes your babies less susceptible to gut damage and autoimmune conditions such as type 1 diabetes5, and allergies, asthma, and airway disease.6

Studies have shown infant gut flora diversity and healthy guts have been linked to less risk of asthma/wheezing, food allergies, and many other autoimmune conditions.5-9 Some data is even suggesting good flora can modulate behavioral and neurodevelopmental disorders.10

Ther-Biotic Women’s Formula

Ther-Biotic for Infants

It’s pretty simple, babies don’t need a large amount of probiotics just a little bit to get their gut started and if you get it early, you don’t may not have to supplement daily later on. Most functional medicine providers and myself recommend either using a Women’s Formula like Ther-biotic® Women’s Formula  by Klaire Labs or their Ther-biotic® Infant Powder.  With the capsules, you can open the capsule and place a small amount of the powder on the breast or the tongue of the infant before feeding, then mom can close the capsule and swallow the rest.

After a few days of that you can also use the infant powder or continue to share yours. They are similar formulas.  The Women’s formula is designed to be the flora that are found in the vaginal canal so it’s just want baby should have swallowed in an ideal world. If baby becomes too gassy after a week or so of the powders, you can start to decrease the dose to 1-2 times per week.

UltraFlora® Baby

OrthoMolecular Saccaromyces product

Metagenics also makes an infant drop called UltraFlora® Baby  that has been easily to use with my son.  If gas becomes an issue with the baby again only give a few times a week after that initial week and consider using a strain called Saccaromyces Boulardii which is a healthy yeast that balances the gut flora and is well known for it’s beneficial effects in acute and chronic GI conditions.11  I is not a gas producing organism.I personally like the OrthoMolecular Saccaromyces product that doesn’t have to be stored in the fridge but Klaire Labs makes one too. There have been case reports of Saccharomyces Boulardii blood stream infections in immunocompromised patients, so I would not recommend use for those patients or premature infants.11

I wish I would have known to give probiotics earlier with my daughter, we started them at about 5 weeks after she was colicky and had reflux. Along with an elimination diet for me, she was lots better!  So it’s not too late even if you are reading this and your child is older they may benefit from replacing gut flora, depending on age, they may need a different formula. Our daughter was allergic to tree nuts, eggs, and a few other things early on, verified by skin prick testing, after a few years of vitamin D and probiotics and eating a gut friendly diet for the most part. The most recent skin test was negative for everything tested! Praise the Lord! She enjoyed splitting a Cashew LaraBar with mom today no problems! Feel free to reach out if you need specific recommendations on probiotics for you or your loved one!

More on gut healing in adults and kiddos to come! Also a post to come on metabolic disease and the gut, early life exposure to antibiotics can influence risk of diabetes and other metabolic conditions like obesity and allergies!12,13

*this post contains affiliate links to products I recommend, all the probiotics recommended in this post can be found in my FullScript Store You do have to set-up a quick account to use. Thanks for supporting the blog, remember 10% goes to support various ministries! Check out My Favorite Things for more details.

References

  1. Lynch S, Pederson O. The human intestinal microbiome in health and disease. N Engl J Med 2016;375:2369-79.DOI: 10.1056/NEJMra1600266.
  2. Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011 Dec;62(6):591-9.
  3. Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, Sogin ML, Li H, Moore JH, Karagas MR. Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants. JAMA Pediatr. 2016;170(3):212-219. doi:10.1001/jamapediatrics.2015.3732
  4. O’Sullivan A, Farver M, Smilowitz JT. The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants. Nutrition and Metabolic Insights. 2015;8(Suppl 1):1-9. doi:10.4137/NMI.S29530.
  5. Endesfelder D, Engel M, Zu Castell W. Gut Immunity and Type 1 Diabetes: a Mélange of Microbes, Diet, and Host Interactions?. Current Diabetes Reports [serial online]. July 2016;16(7):60. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017 doi:10.1007/s11892-016-0753-3.
  6. Huang et al. Breastfeeding and timing of first dietary introduction in relation to childhood asthma, allergies, and airway diseases: A cross-sectional study. Journal of Asthma. 2016; Published on-line 07 Sept 2016. P 1-10. http://dx.doi.org/10.1080/02770903.2016.1231203
  7. Uusitalo U, Liu X, Virtanen S, et al. Association of Early Exposure of Probiotics and Islet Autoimmunity in the TEDDY Study. JAMA Pediatrics [serial online]. January 2016;170(1):20-28. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017.
  8. Arrieta M, Stiemsma L, Finlay B, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Science Translational Medicine [serial online]. September 30, 2015;7(307):307ra152. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017.
  9. Fujimura K, Sitarik A, Lynch S, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine [serial online]. October 2016;22(10):1187-1191. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017.
  10. Hsiao E, McBride S, Mazmanian S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell [serial online]. December 19, 2013;155(7):1451-1463. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017.
  11. Kelesidis T, Pothoulakis C. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therapeutic Advances in Gastroenterology. 2012;5(2):111-125. doi:10.1177/1756283X11428502
  12. Yallapragada S, Nash C, Robinson D. Early-Life Exposure to Antibiotics, Alterations in the Intestinal Microbiome, and Risk of Metabolic Disease in Children and Adults. Pediatric Annals [serial online]. November 2015;44(11):e265-e269. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017
  13. Johnson C, Ownby D, Joseph C, et al. Antibiotic exposure in early infancy and risk for childhood atopy. The Journal Of Allergy And Clinical Immunology [serial online]. June 2005;115(6):1218-1224. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 19, 2017.