9/5/2019

A wise man once said…..

Functional Medicine and the Gut

Jana Roso MSN, RN, CPNP Neuronutrition Associates

1 2

How the gut influences other organs

• Bacteria in the gut ”educate” the immune system and maintain balance

• Absorbs and synthesizes vitamins

• Protects against pathogens

• Produces neurotransmitters

• Produces short chain fatty acids

• Communicates with the brain and liver

• Contains 70% of our immune system

3 4

5 6

1 9/5/2019

The gut-brain connection

“Gut microbes influence energy, glucose, Communication exists between your gut and and lipid homeostasis by controlling the brain--> ”butterflies in your stomach” endocrine, enteric and nervous system routes. These dialogues are discussed in the context of brain pathologies and Physical connection via the Vagus nerve. A neurodegenerative disorders” study in mice found that feeding them a probiotic reduced cortisol in blood, unless the vagus nerve was cut, then the probiotic had no effect.

7 8

The gut-brain connection So, how do we Neurotransmitter production in the gut affects know the gut is mood→ 80% Serotonin produced in gut healthy??

Short chain fatty acids, such as butyrate, and the microbes that produce it are also important for forming the blood-brain barrier More importantly, how do we keep it healthy??

9 10

Gut permeability

Root cause→

Consequences→

11 12

2 9/5/2019

13 14

15 16

5 ”R” Gut Protocol

REMOVE Stressors: allergenic foods, parasites, bacteria, yeast

REPLACE Add back in enzymes, HCL, bile acids

REINOCULATE Pre and pro-biotics

REPAIR Add nutrients to help heal- zinc, glutamine, antioxidants, colostrum, omegas

REBALANCE Balance stress, sleep, and exercise

17 18

3 9/5/2019

Food sensitivities vs allergies

IGE reaction (Allergy) -Rapid onset- within 30 min- 1 hour -Wheezing, coughing, throat irritation, nausea, cramping, swelling of face -Fixed food allergy -Exposure 2nd or 3rd time can elicit a worse response

IGG reaction (Sensitivity) -Delayed onset (4-72 hours later) -Largest circulating antibody in immune system; can cross placenta -Can contribute to chronic health conditions -Hard to identify unless tested

19 20

Constipation

Deficiency in Miralax?

Common OR childhood A great opportunity to gastrointestinal investigate what could concerns be causing slow motility and improper detoxification

21 22

Speaking of Miralax…. Miralax use

Polyethylene glycol 3350 is intended for use in patients 17 years of age and older, but it has been prescribed "off-label" for many years to children for relief.

Most children are taking this chronically for their constipation

Between 2007 and 2017, 1564 adverse symptoms were reported on 645 children between the ages of 0‐21. Of these, 919 were neurological, 770 of these were neuropsychiatric, such as anxiety, anger, and abnormal behavior

GOAL- If using Miralax, use for the shortest time possible, while discovering the underlying cause of constipation

23 24

4 9/5/2019

Nutraceuticals for constipation -Address diet and fiber intake

Fiber supplementation: 1-4 g daily x 4 weeks -Remove high IGE/IGG foods -increases stool frequency -Can cause abd pain, gas, loose stools

2012 meta analysis showed that fiber increase showed significant advantage over placebo in -Encourage water intake stool frequency. Addressing Constipation Magnesium Citrate: -Add Magnesium citrate 200-1000 mg daily -bowel prep, osmotic -can cause abd cramping, gas, or electrolyte imbalance “Just as effective as Miralax for constipation and fecal impaction” -Add Omega fatty acids and Vitamin C Fish Oil/ Omega 3 fatty acids: 2,000- 6,000 mg daily given orally -Consider stool study testing -Helps with inflammation, lubrication of intestines, and increases butyrate- which reduces pain with defecation

25 26

Nutraceuticals for constipation

Vitamin C: 2,000-4,000 mg daily -Unabsorbed vitamin C has an osmotic effect in your digestive tract. -can cause flushing, headache, nausea, ,

Fruit/plant extracts: 10 Plums or prunes per day 6 g fruit blend “Ready, Set, Go” “A review from 2013 showed that prunes contain sorbitol and has a laxative effect”

Aloe Vera Juice: 0.04-0.17 g daily taken orally “The latex of Aloe Vera contains a compound known as barbaloin (an anthraquinone) which stimulates peristalsis and provides a laxative effect”

27 28

Diarrhea

29 30

5 9/5/2019

Nutraceuticals for diarrhea -Address diet

-Colostrum: -Remove high IGE/IGG foods Infectious diarrhea- 7 g three times daily x 14 days Prevention- 3 g once daily Helps Maintain Microbial Balance -Encourage relaxed eating habits Supports GI Barrier Health and Integrity Helps Maintain Normal Inflammatory Balance Addressing “The frequency of stools in children who received bovine colostrum decreased significantly Diarrhea (seven daily vs. 2.5 daily) after 48 hours of treatment” -Add Colostrum and L Glutamine -Saccharomyces Boulardii: Infectious diarrhea- 250 mg twice-three times daily x 5 days -Inhibits Toxin A mediated diarrhea, intestinal inflammation; releases protease that cleaves -Add Zinc, Peppermint, probiotics C diff toxins; inhibits IL-8 production; alters structure of H Pylori; increases SCFA production; increases secretory IGA levels

-Consider stool study testing

31 32

Nutraceuticals for diarrhea Nutraceuticals for diarrhea

-Lactobacillus Reuteri: -Lactobacillus rhamnosus 7-20 billion strains once daily x 4-8 weeks 10 billion strains x 4-10 days -can produce antimicrobial molecules -able to inhibit the colonization of pathogenic microbes and remodel the -enhances immune response commensal microbiota composition in the host -downregulates the secretory and motility defenses designed to remove perceived -can reduce the production of pro-inflammatory cytokines while noxious substance promoting regulatory T cell development and function -inactivates viral particles -alleviates the effects of pro-inflammatory cytokines like TNF-α and interferon-γ on epithelial barrier integrity and inflammation 2018 study-The mean (SD) duration of watery diarrhea after treatment was 1.7 (1.6) days in the L. reuteri group and 2.9 (2.3) days in the placebo group (p = 0.07). On the second day of treatment only 26% of patients receiving L. reuteri had 2014 study- There was significant reduction in average number of stools per day watery diarrhea, compared with 81% of those receiving placebo in LGG group (P<0.001) compared to the control group. These benefits were seen irrespective of rotavirus positivity in stool tests.

33 34

Nutraceuticals for diarrhea Nutraceuticals for diarrhea

-Peppermint: -L Glutamine: 0.2 mL of peppermint oil per capsule twice daily 15-45 g daily -antispasmodic effects and calming effects on the gastrointestinal tract -promotes gut mucosal integrity by acting as an energy source and preventing bacterial translocation; has anti-inflammatory properties; prevents gut Study- examined 57 people with IBS/diarrhea who received either enteric-coated permeability; enhances nutrient absorption; increases blood flow to the gut lining peppermint capsules or placebo twice a day for 4 weeks. Of the people who took peppermint, 75% had a significant reduction of IBS symptoms. -can be metabolized into glutamate **

-Zinc: Study- In patients with IBS-D with intestinal hyperpermeability following an enteric 20 mg for 10-14 days infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. -restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels

Study by WHO and UNICEF the effect of zinc supplementation on diarrheal diseases found preventive and long-lasting impact

35 36

6 9/5/2019

37 38

Reflux

39 40

-Address diet of mom (if breastfeeding) or Nutraceuticals for reflux child -Mastic Gum 350 mg twice-three times daily x 4 weeks -Remove IGE/IGG foods -Anti-oxidant, anti-microbial, and anti-inflammatory effects; also kills H Pylori bacteria

-Consider hypochlorhydria as a cause 2010 study- Individual symptoms that showed significant improvement with mastic gum were: stomach pain in general, stomach pain when anxious, dull ache in the Addressing upper abdomen and reflux -Add Mastic Gum, Betaine HCL -Betaine HCL 500 mg taken with meals; can increase slowly -Increases the acidity in the stomach; can help inhibit overgrowth of candida and help with treatment of SIBO -Add marshmallow root, DGL -should not be used at the same time as aspirin, ibuprofen, corticosteroid drugs, or other anti- inflammatory medications

2013 study- After gastric pH > 4 was confirmed for 15 min, 1500 mg of betaine HCl was given -Add low dose melatonin orally with 90 mL of water and gastric pH was continuously monitored for 2 h. Betaine HCl significantly lowered gastric pH by 4.5 units during the 30 min interval after administration

41 42

7 9/5/2019

Nutraceuticals for reflux Nutraceuticals for reflux

-Marshmallow root: 500 mg daily -high in mucilage and its slippery nature soothes irritated mucus membranes of -Melatonin: the digestive tract 2-5 mg daily for 4-8 weeks 2011 study found that Marshmallow root demonstrated potential benefits in treating gastric ulcers in rats -protects against GI ulcerations and esophageal lesions -acts as a free radical scavenger, as well as to lower gastric acid secretion and -DGL (Deglycyrrhizinated licorice): increase lower esophageal sphincter (LES) pressure through multiple mechanisms 400 mg chewable tablet prior to meals -soothing anti-inflammatory herb that raises the concentration of prostaglandins, 2008 study- in subjects with gastroesophageal reflux disease (GERD), the which promote mucous secretion, stabilize cell membranes, and stimulate new cell combination of melatonin with other natural supplements was found to be growth superior to omeprazole, a proton pump inhibitor (PPI)

2017 study showed that DGL was associated with significant improvement in symptoms of gastric and intestinal irritation and that these improvements were consistently reported as better than commonly used .

43 44

45 46

Additional gut support Additional gut support

-Digestive enzymes: -Prebiotics: 1 capsule or chewable with each meal 1/8-1 tsp powder mixed into drink daily -supports the optimal breakdown of the food eaten each and every day. When -nondigestible food components that selectively stimulate the growth or activity food is not properly digested one can experience a variety of consequences such of desirable microorganisms as gas, , occasional , and undigested food in stool. -Increases “good” bacteria in the gut and decreases “bad,” unwanted bacteria -Foods such as onion, garlic, asparagus, chicory root, and jicama are all high in -Broad spectrum probiotics: prebiotics 1 capsule or ½ tsp powder daily in evening -Increases beneficial bacteria in the large intestine, helps lower inflammation, -Biocidin (bilberry, noni, milk thistle, willow bark, grape seed) supports the immune system, can improve mood Liquid or capsule options- work up on dose -can be found in yogurt and other fermented foods 1 drop per 10 lbs body weight for children -The most common are bacteria that belong to groups called Lactobacillus and -supports microbiome balance for healthy digestion and elimination Bifidobacterium -addresses biofilms and can lower yeast, viral load, and bacterial load -Has been shown to help lower several inflammatory cytokines

47 48

8 9/5/2019

Additional gut support

-Alinia (Nitazoxanide) 200-500 mg twice daily x 3 days -Anti-parasitic, treatment of H pylori, gram negative overgrowth, C diff, and SIBO -Can cause urine to turn neon yellow; some cramping and abd discomfort

2006 study- Thirty-four patients with C diff received Flagyl at a dosage of 250 mg 4 times per day for 10 days, 40 patients received Alinia at a dosage of 500 mg 2 times per day for 7 days, and 36 patients received Alinia at a dosage of 500 mg 2 times per day for 10 days. After 7 days of treatment, 82.4% had responded to Flagyl therapy, compared with 89.5% who had received Alinia therapy.

-Rifaximin (Xifaxan) > 12 yrs 200 mg three times daily x 3-20 days -non systemic antibiotic that treats C diff, SIBO, and E coli infectious diarrhea -expensive; often not covered by insurance; can cause nausea and abd pain

2018 study- the positive response rate to Rifaximin for patients with either hydrogen or hydrogen and methane positive breath testing for SIBO in our population was 54.2%

49 50

51 52

The future in gut health Case Study

18 mth old male Fecal transplants!! -FT vag delivery; BF -Transplanting feces from a healthy donor into another person to restore the balan ce of bacteria in their gut. -Chronic loose and foul smelling stools (>4 months) -Fecal transplants may help treat gastrointestinal infections and other conditions.

-Currently approved in US for recurrent C diff infections -Poor appetite

-While the overall cure rate for recurrent diarrheal infection exceeds 90%, trials of -Disrupted sleep at night and waking early in AM fecal transplantation for other conditions like inflammatory bowel disease exacerbations and type 2 diabetes have had much more mixed results, averaging nearer 20% -Fussy and clingy

53 54

9 9/5/2019

Case Study

18 mth old male

-Gluten/dairy free at home

-Loves avocados, potatoes, and carbs!

-No previous labs done

55 56

57 58

Case Study Results

DX: + Giardia and low beneficial bacteria (dysbiosis) -No longer fussy Treatment plan: -Alinia 100 mg twice daily x 3 days (had to repeat course in this -Stools appear formed after 6 days on Alinia and gut child) supporting supplements

-Colostrum powder ½ tsp daily in AM to help with inflammation, -Foul smell of stools is gone loose stools, and healing gut lining -Sleeping through the night -Pre-biotic fiber (Inulin) to feed beneficial bacteria- ¼ tsp daily in AM -Appetite increased and trying new foods

-Broad spectrum probiotic ½ tsp powder in evening

59 60

10 9/5/2019

Results

Repeat stool study 2 months later

61 62

References

Aggarwal, S., Upadhyay, A., Shah, D., Teotia, N., Agarwal, A., & Jaiswal, V. (2014). Lactobacillus GG for treatment of acute childhood diarrhoea: an open labelled, randomized controlled trial. The Indian journal of medical research, 139(3), 379–385.

Bajait, C., & Thawani, V. (2011). Role of zinc in pediatric diarrhea. Indian journal of pharmacology, 43(3), 232–235. doi:10.4103/0253-7613.81495

Baker SS, Liptak GS, Colletti RB, Croffie JM, Di Lorenzo C, Ector W, et al. Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition [published correction appears in J Pediatr Gastroenterol Nutr 2000;30:109]. J Pediatr Gastroenterol Nutr 1999;29:612-26.

Bardhan, K. D., Strugala, V., & Dettmar, P. W. (2012). Reflux revisited: advancing the role of pepsin. International journal of otolaryngology, 2012, 646901. doi:10.1155/2012/646901

Coëffier, MoïseDéchelotte, PierreDucrotté, Philippe et al. Intestinal Permeability in Patients With Diarrhea- Predominant Irritable Bowel Syndrome: Is There a Place for Glutamine Supplementation? Gastroenterology, Volume 148, Issue 5, 1079 - 1080

Dabo Xu & Chung Owyang, 2018. "Rifaximin for Treatment of Small Bowel Bacterial Overgrowth," Current Resources Trends In Gastroenterology And Hepatology, Lupine Publishers, LLC, vol. 1(3), pages 57-60, September.

Daniel M. Musher, Nancy Logan, Richard J. Hamill, Herbert L. DuPont, Arnold Lentnek, Arvind Gupta, Jean- Francois Rossignol, Nitazoxanide for the Treatment of Clostridium difficile Colitis, Clinical Infectious Diseases, Volume 43, Issue 4, 15 August 2006, Pages 421–427

63 64

References References

Guttner, Y., Windsor, H. M., Viiala, C. H., Dusci, L., & Marshall, B. J. (2003). Nitazoxanide in Pashankar DS, Bishop WP. Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of Helicobacter pylori: a clinical and in vitro study. Antimicrobial agents and treatment of constipation and encopresis in children. J Pediatr. 2001;139:428‐432 chemotherapy, 47(12), 3780–3783. doi:10.1128/aac.47.12.3780-3783.2003 Philichi, Lisa MN, ARNP; Yuwono, Melawati MD Gastroenterology Nursing: March/April 2018 - Iacono G, Cavataio F, Montalto G, Florena A, Tumminello M, Soresi M, et al. Intolerance of Volume 41 - Issue 2 - p 141–144 cow’s milk and chronic constipation in children. N Engl J Med 1998;339:1100-4. Pituch, A., Walkowiak, J., & Banaszkiewicz, A. (2013). Butyric acid in functional constipation. Kelesidis, T., & Pothoulakis, C. (2012). Efficacy and safety of the probiotic Saccharomyces Przeglad gastroenterologiczny, 8(5), 295–298. doi:10.5114/pg.2013.38731 boulardii for the prevention and therapy of gastrointestinal disorders. Therapeutic advances in gastroenterology, 5(2), 111–125. doi:10.1177/1756283X11428502 Strickler A, Kolmer JA, Schamberg JF: Complement fixation in acne vulgaris. J Cutaneous Dis 1916, 34:166-78 Kines, K., & Krupczak, T. (2016). Nutritional Interventions for Gastroesophageal Reflux, Irritable Bowel Syndrome, and Hypochlorhydria: A Case Report. Integrative medicine (Encinitas, Calif.), Vandenplas Y. Lactobacillus reuteri is an effective option for the prevention of diarrhoea in 15(4), 49–53. preschool children but may not be cost-effective in all settings BMJ Evidence-Based Medicine 2014;19:212. Loening-Baucke V, Miele E, Staiano A. Fiber (glucoman-nan) is beneficial in the treatment of childhood constipation. Pediatrics 2004;113(3 pt 1):e259-64 Yang, J., Wang, H. P., Zhou, L., & Xu, C. F. (2012). Effect of dietary fiber on constipation: a meta analysis. World journal of gastroenterology, 18(48), 7378–7383. doi:10.3748/wjg.v18.i48.7378 M. Stacewicz-Sapuntzakis (2013) Dried Plums and Their Products: Composition and Health Effects–An Updated Review, Critical Reviews in Food Science and Nutrition, 53:12, 1277-1302, DOI: 10.1080/10408398.2011.563880 Zhang H, Yu L, Yi M, Li K: Quantitative studies on normal flora of seborrhoeic dermatitis. Chin J Dermatol 1999, 32:399-400

65 66

11