Unraveling the Complexity of Functional GI Concerns: Understanding Types, Causes and Solutions


1. Symptoms, Prevalence, and Subtypes of Functional GI Concerns

2. Underlying Causes of Functional GI Concerns

  • 2.1. Food Sensitivity/Leaky Gut
  • 2.2. Microbial Balance in the GI Tract
  • 2.3. Spoiled Food
  • 2.4. Mast Cell Activation
  • 2.5. Low Stomach Acid and Digestive Enzymes
  • 2.6. Genetic Factors
  • 2.7. Gut-Brain Connection

3. Assessments for Functional GI Concerns

  • 3.1. IgG Food Sensitivity Testing
  • 3.2. 3-Hour Breath Test
  • 3.3. Auto Antibody Testing
  • 3.4. Biopsies with CD117 Staining

4. Nutrients to Support Functional GI Concerns

  • 4.1. Glutamine
  • 4.2. Herbal Ingredients
  • 4.3. Betaine HCl & Digestive Enzymes
  • 4.4. Probiotics
  • 4.5. Fiber
  • 4.6. Butyrate

5. Key Takeaways

  • 5a. Lifestyle
    • Stress Management
    • Exercise
  • 5b. Diet & Nutrition
    • Low FODMAP Diet
    • High-Fiber Foods

6. Pure Encapsulations® Nutrient Solutions

  • 6.1. Probiotic G.I.
  • 6.2. PureGG 25B
  • 6.3. PureBi*OmeTM Intensive
  • 6.4. Poly-Prebiotic Powder
  • 6.5. Epi-Integrity Powder
  • 6.6. SunButyrateTM-TG liquid
  • 6.7. Digestive Enzymes Ultra with Betaine HCl
  • 6.8. Digestive Enzymes Ultra
  • 6.9. Betaine HCl
  • 6.10. MicroDefense w/ Oregano


Symptoms that involve abdominal discomfort, bloating, flatulence and occasional diarrhea or constipation are functional GI concerns that have an estimated worldwide prevalence of up to 1 in 10 individuals,1 making them the most common functional bowel concerns worldwide. Impacting approximately three times as many women as men,2 functional GI concerns can occur at any age, with 50% of patients experiencing symptom onset before 35 years.3

Functional GI concerns are characterized by abdominal discomfort coupled with altered bowel habits and are also associated with visceral hypersensitivity, altered motility, immunomodulation, altered gut microbiota and dysregulation of the gut-brain axis. Functional GI concerns can be differentiated into subtypes determined by an individual’s predominant clinical manifestation: occasional diarrhea, occasional constipation, or mixed symptoms – primarily constipation with intermittent episodes of diarrhea.


Due to the heterogeneous nature of functional GI concerns, symptoms and severity can vary within each subtype and from individual to individual, negatively impacting a person’s quality of life. An individual with functional GI concerns will often describe uncertainty about what foods trigger their symptoms, state the difficulties of eating out and express fear of experiencing symptoms in social situations.

Although no single causative factor has been isolated for functional GI concerns, several etiologies have come to the forefront of investigations.


The intestinal barrier serves an important function of being a selectively permeable barrier between environmental exposures and systemic circulation. Intercellular tight junctions are the key structures that regulate paracellular trafficking of macromolecules through the intestinal barrier. Disturbance of this barrier, also popularly termed as “leaky gut,” allows antigens in the form of Lipopolysaccharides and bacterial components, which would otherwise be restricted to the gut, to gain access to the mucosa and systemic circulation, triggering immune activation and cytokine release.4, 5 Proteins that contribute to the stability of tight junctions and barrier function, like occludin, claudin, cadherin and zonulin, are a factor in leaky gut and have been implicated in functional GI concerns.4-6 This may in turn contribute to higher stool frequency, visceral sensitivity and an increase of symptoms in patients, especially those with occasional diarrhea.6, 7

It has been suggested that IgG-mediated food sensitivities have a role in functional GI concerns.8, 9, 10

The intestinal permeability biomarkers, anti-lipopolysaccharide (LPS) and anti-occludin IgG and IgA antibodies have been significantly and positively associated with IgG-mediated food sensitivities, and a higher prevalence of food sensitivity has been found in patients with functional GI concerns. In a randomized, controlled trial and two studies utilizing exclusion diets, researchers observed greater numbers of food-specific IgG antibodies in individuals with functional GI concerns vs. controls.8-10 Serum zonulin, another biomarker for leaky gut, has also been observed to be increased in patients with occasional diarrhea or mixed symptoms compared to healthy controls.7, 11


A study published by Su and colleagues in 2023 examining the functional composition of gut microbiota of 942 subjects with varying subtypes of functional GI concerns who were enrolled in the American Gut Project determined that bacterial diversity of patients with functional GI concerns was lower than that of healthy controls, with all subtypes showing a deficiency of beneficial bacteria and enrichment of non-beneficial microorganisms.12

A reduction in Bifidobacteria and Lactobacillus,has been observed in patients with functional GI concerns and in patients with occasional diarrhea and mixed symptoms, along with a reduction in butyrate-producing microorganisms.13, 14

Aberration of the gut microbiota and its metabolites can disrupt the integrity of the intestinal barrier and its secretions can affect the gut-brain axis, contribute to visceral sensitivity, altered motility, and promote the development of symptoms related to functional GI concerns.12

Disturbance of microbial balance in the GI tract or small intestine is a prominent contributor to functional GI concerns, with one meta-analysis finding a 31% prevalence compared to controls.15 The strongest association is seen in diarrhea, with some investigations revealing the presence of a microbial imbalance in more than 80% of patients with occasional diarrhea.16

The fermentation of carbohydrates by gut microbiota can produce gases like hydrogen and methane, contributing to the overlapping symptoms of occasional abdominal discomfort, distension, occasional diarrhea and bloating, as seen between microbial imbalance and functional GI concerns.

A positive association and significant prevalence have been established between methane positivity on lactulose breath tests and occasional constipation.17, 18


Every year, 1 in 6 U.S. adults is affected by food quality issues according to the CDC.19

Spoiled food exposure affecting the digestive tract are among the greatest risk factors for developing functional GI concerns, with affected individuals having a four times higher risk of functional GI concerns than nonexposed individuals.20 Women and individuals with psychological distress at the time of an episode are at an increased risk of developing functional GI concerns post-exposure.20


Abundant in the intestinal landscape, mast cells and their mediators have been implicated in the study of functional GI concerns and can be provoked by exposure of non-beneficial microorganisms, food antigens, cytokines and even psychological stress.21

When activated, they release various mediators, including histamine, serotonin, protease, leukotrienes, prostaglandins, cytokines, TNF and platelet-activating factors.

An increased number of mast cells in the colon and mucosa of the small intestine has been observed both in patients with occasional diarrhea or occasional constipation vs. controls.21, 22 Owing to their proximity to enteric and pain transmitting afferent nerves, individuals with an increased activity of these mast cells can experience visceral hypersensitivity, along with altered motility, immune activation and increased barrier permeability.21, 22


Gut microbiota can quickly overpopulate given the right environment. Insufficient stomach acid or digestive enzyme production can create an environment that prevents proper digestion and absorption.23, 24 Adequate stomach acid is required to absorb multiple micronutrients, including calcium, magnesium, iron and several B vitamins.23 Inadequate digestion can lead to altered motility, altered microbiota, fermentation by microbes and symptoms of bloating and discomfort seen in functional GI concerns discussed here, and in other overlapping gastrointestinal conditions.24, 25


Case-control and prospective studies have shown that patients with functional GI concerns frequently report a positive family history of functional GI concerns.26, 27, 28

Genome-wide association studies have investigated possible genetic variations in signaling pathways that could increase susceptibility to functional GI concerns. One such pathway, the serotonergic pathway, has received significant attention. Polymorphisms in the 5-HT3 receptor family and disrupted serotonergic function have been linked to a greater degree of visceral hypersensitivity and increased susceptibility to functional GI concerns, especially in women.2

With greater than 90% of the body’s production taking place in the gut, serotonin or 5-HT, regulates motility, secretion and visceral sensation. It also performs as a neurotransmitter, paracrine factor, endocrine hormone and growth factor, and interacts with the vagus nerve. Serotonin’s interaction with the vagus nerve influences emotional processing, behavior and the immune and nervous system. Variants in the 5-HT3 receptor family have been associated with concerns related to mood because they are co-occurringwith functional GI concerns.2


The significance of the gut-brain axis in functional GI concerns has been well established. This bidirectional relationship influences the onset and course of functional GI concerns and partly accounts for the great amount of co-occurring psychological concerns. The risk of occasional nervous tension and mood concerns in patients with functional GI concerns is threefold compared to healthy controls29 and at least 50% of patients with functional GI concerns describe occasional nervous tension or mood concerns.30

Compared to healthy controls, patients with functional GI concerns have a greater reactivity to stress,15, 30 which induces alterations in:

  • gastric motility
  • autonomic tone
  • HPA axis response
  • visceral perception
  • microbial composition

The existence of stress and mood concerns have also been linked to onset of symptoms after an episode of non-beneficial microorganism exposure affecting the digestive system, with mixed symptoms of occasional constipation and occasional diarrhea being the greatest risk following exposure.



Two-thirds of patients with functional GI concerns report that dietary factors trigger their symptoms12 and there is increasing evidence suggesting that IgG hyperreactivity plays a role in functional GI concerns.

In numerous clinical trials where food exclusion diets were implemented based on foods identified as having IgG antibodies with ELISA testing, symptom improvement was seen in patients with functional GI concerns.8-11, 31 Significant improvements most often seen were:

  • bloating
  • diarrhea frequency
  • abdominal discomfort
  • feelings of distress
  • stool shape/consistency

Patients experiencing functional GI concerns often cannot predict what foods may trigger them or when their symptoms will be aggravated, which can limit their social activity. Incorporating food sensitivity testing may lessen this burden and assist patients with personalizing their diet and nutrient needs.


Breath tests involving ingestion of a lactulose solution are a noninvasive way to measure exhaled hydrogen and methane gases and are used to determine disruption of the balance of microbiota.

For those patients with occasional constipation or slower transit time, the 3-hour assessment can discern gas levels over a more extended period. The 3-hour profile is also useful in pinpointing the possible presence of hydrogen sulfide gas, indicated by a flat line at the 3-hour mark.


Non-beneficial bacteria that are often elevated in patients with occasional diarrhea or mixed symptoms: anti-CdtB and anti-vinculin.  An auto antibody test can detect elevated levels of these biomarkers and determine subtypes within functional GI concerns.32, 33


Patients with functional GI concerns commonly experience occasional dyspeptic symptoms. A jejunal biopsy with CD117 staining can be utilized to determine mast cell numbers and activity in the mucosa of the proximal small intestine.34


Glutamine: Glutamine, the most abundant amino acid in the body, is a primary energy source for intestinal epithelial cells and is utilized by the body for tissue repair and gastrointestinal support.35, 36, 37 Glutamine plays a large role in maintaining healthy intestinal integrity by enhancing the intestine’s protective mucosal lining.38

Herbal Ingredients: With the high prevalence of microbiota imbalance in the GI tract and small intestine seen in functional GI concerns, employing strategies to shift this balance may be warranted in some patients. Botanicals like artemisia, olive leaf extract, oregano, clove and berberine sulfate can help promote healthy microbial balance.39, 40, 41, 42, 43

Betaine HCL & Digestive Enzymes: Hypochlorhydria or achlorhydria and reduced digestive enzyme production can lead to malabsorption of nutrients, inadequate digestion, potential food sensitivities, altered microbiota and digestive discomfort and bloating.24, 25 In patients where either of these are a factor, Betaine HCl may be used at mealtime to support optimal gastric pH, enhance digestion of protein and other nutrients to support daily wellness and neurotransmitter synthesis.44, 45 The use of digestive enzymes can also support the digestion and absorption of proteins, carbohydrates, fats and fibers not acted upon by the gastric environment.

Probiotics: Probiotics are efficacious in all subtypes of functional GI concerns, although specific strains should be considered for each subtype and symptoms presented. Overall, meta-analyses have shown that probiotics may support stool consistency, regulate stool frequency and gut transit time, and support symptoms related to functional GI concerns.46, 47, 48‡

Fiber: Owing to contradictory outcomes in clinical studies and the multifactorial nature of functional GI concerns, using fiber has experienced a pendulum effect. While fiber intake is typically deficient in individuals with functional GI concerns, and both soluble and insoluble fiber can aggravate symptoms, studies examined by meta-analyses seem to favor using soluble fiber.49, 50‡
Psyllium husk, a valued source of soluble fiber, helps promote larger and softer stools for healthy bowel movement frequency. It is fermented in the intestines, producing short-chain fatty acids (SCFAs) that provide an energy source for the colon to maintain healthy colon cell function and promote beneficial microflora.51‡
Prebiotic fibers, like arabinogalactan, are nondigestible food components that modulate and support the gut microbiota. They perform beneficial metabolic, trophic and protective functions within the gut, leading to overall cellular, immune and metabolic support.52 Arabinogalactan may increase the concentration of beneficial bacteria, such as Bacteroidetes and Faecalibacterium prausnitzii.53‡
When recommending a fiber supplement to patients with functional GI concerns, practitioners should consider the fiber type and symptoms. It’s advisable to start “low and slow” with fiber supplementation, adding small amounts of fiber gradually over several weeks, monitoring symptoms and ensuring adequate hydration. Some patients respond better to increased fiber when they are in the later stages of gut healing.

Butyrate: Butyrate is one of the three most abundant short-chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of polysaccharides/fiber in the colon, where it serves as an energy source for epithelial cells.54 Butyrate plays a major role in intestinal physiology, supporting both physical and biochemical protective barrier function, bowel motility, nutrient absorption and immune activity of intestinal cells.55 It also promotes the proliferation, differentiation and renewal process of the colonocytes. This trophic property of butyrate and other SCFAs support tight-junction assembly, healthy mucus production and a healthy intestinal barrier.56‡


The heterogeneity of functional GI concerns requires that patients receive a comprehensive, individualized approach, accounting for symptom type and fluctuation, co-occurring conditions and nutrient needs. Therapeutic options should include personalized dietary changes, supplemental support and lifestyle modifications.



Stress Management: Patients with functional GI concerns who have stress compared to those not exposed to stressful events should make stress management a vital component of their support plan.57
Patients receiving advice on stress management techniques as part of a stress management program have reported support for symptoms and quality of life.57
Given the high prevalence of stress and mood concerns in patients with functional GI concerns, certain therapies may also provide a benefit for these patients. One option is cognitive behavioral therapy (CBT). CBT can improve cognitive flexibility and may support symptom severity, especially abdominal discomfort, particularly in patients with functional GI concerns.

Regular Exercise: The benefits of regular exercise go beyond just improving physical health. Regular exercise can evoke feelings of well-being, enhance cognition, reduce stress and support mental health by improving symptoms of occasional nervous tension and low mood.
In a pilot study and two randomized, controlled studies examining physical activity for functional GI concerns, both regular engagements in low-impact and high-intensity exercise had beneficial effects on symptoms and feelings of well-being in individuals with functional GI concerns compared to controls.59, 60, 61 Individuals with functional GI concerns experienced increased quality of life, reduced mood concerns and occasional nervous tension.59-61 Regular exercise in these studies ranged from yoga and walking to cycling, aerobics and swimming.
These outcomes support the benefits of regular physical activity in patients with functional GI concerns and underpin the argument that physical activity recommendations can meet patients “where they are” in terms of fitness level, motivation and ability.


Low FODMAP Diet: The low FODMAP Diet has gained increasing popularity among patients with functional GI concerns and some healthcare practitioners.
FODMAP stands for Fermentable, Oligo-,Di, Monosaccharides And Polyhydric alcohols. FODMAPS encompass foods that can interact with gut microbiota and through fermentation, can provoke symptoms of discomfort, flatulence and dysregulated bowel habits like those seen in functional GI concerns. This category of food includes lactose, fructose, fructans and other poorly absorbed carbohydrates.
Overall, symptom improvement has been seen in some patients adhering to a Low FODMAP diet, with reductions in abdominal discomfort frequency and severity, bloating, and improved satisfaction with bowel habits and quality of life, compared to a standard diet consisting of high FODMAP foods.62,63
When recommending a Low FODMAP diet, a few things should be considered. One is the effect on the gut microbiome. FODMAPS are a food source for colonic microbiota, which degrade them into short-chain fatty acids. Deprivation of these carbohydrates can affect the production of SCFAs and reduce bacterial counts like Bifidobacteria, consequently affecting the integrity of the mucosal barrier.64
Additionally, the Low FODMAP diet is quite restrictive and long-term adherence may affect nutrient status and prove expensive, difficult and frustrating for the patient. Utilizing a Low FODMAP diet as a therapeutic option should be undertaken in three distinct stages: elimination, reintroduction, and personalization. Once Low FODMAP foods have been eliminated and patients see symptom improvement, they should be guided on how to reintroduce individual FODMAP foods back into their diet gradually, and the patient’s tolerance or reaction to that food should be assessed. It’s important to remember that different FODMAP foods affect different functional GI concerns and their subtypes differently. Taking the time to assist the patient through the reintroduction phase provides an opportunity to personalize their diet and for a greater variety of tolerable foods to be added to their diet over time.

High Fiber Foods: To echo Lucretius from De Rerum Natura: “What is food to one, is to others bitter poison.”
Fiber may pose the same challenge in patients with functional GI concerns. While it is recommended that men and women consume 38g and 25g of fiber daily, most patients with functional GI concerns have suboptimal fiber intakes.
As seen with fiber supplementation, dietary soluble fiber is more beneficial for patients with functional GI concerns. When incorporating more dietary fiber, the type, amount and method of preparation are important.

  • Type: Foods high in soluble fiber and low in insoluble fiber are less aggravating to symptoms
  • Amount: Fiber with adequate hydration should be introduced in small amounts over several weeks.
  • Preparation: Patients may find high-fiber foods are less tolerable when eaten raw and more tolerable when cooked or pureed.



  • Probiotic G.I. is shelf stable and provides 10 billion CFU per capsule of beneficial bacterial strains in thre Lactobacillus and Bifidobacteria genuses. This probiotic supports GI barrier function and helps to maintain the integrity of the intestinal mucosa. Suggested use: 1 capsule, 1-2 times daily, with or between meals.
  • PureGG 25B contains shelf-stable, highly researched Lactobacillus rhamnosus that supports immune, GI and overall health. Suggested use: 1 capsule daily, with or between meals.
  • PureBi*OmeTM Intensive is a high-potency, 4-strain, clinically researched proprietary probiotic blend combined with Saccharomyces boulardii to support intestinal microbial balance and help lessen the occurrence of occasional diarrhea. Suggested use: 1 capsule daily, with a meal.
  • Poly-Prebiotic Powder is a unique powdered blend of researched prebiotic fibers and polyphenols to support gastrointestinal, cellular and immune function by boosting bifidobacteria and microbiome diversity. Suggested use: 1 scoop, 1-2 times daily, mixed with a beverage or into food.


  • Epi-Integrity Powder promotes healthy modulation of mucosal immune responses to support GI integrity. Suggested use: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice.
  • SunButyrateTM-TG liquid provides 875 mg of short-chain fatty-acid butyric acid in one teaspoon to promote gut-barrier integrity, cytokine balance in the GI tract, abdominal comfort and bowel motility. Suggested use: 1 teaspoon, 1-3 times daily, with meals.
  • L-Glutamine delivers 850 mg of L-glutamine to support the mucosal lining and healthy functioning of the gastrointestinal tract; it may help to maintain lean muscle mass. Suggested use: 1 capsule, 1-3 times daily, between meals. Also available in powder.


  • Digestive Enzymes Ultra with Betaine HCl helps maintain optimal gastric pH and delivers a comprehensive blend of vegetarian digestive enzymes to support protein, carbohydrate, fat, fiber and dairy digestion. Suggested use: 2 capsules with each meal.
  • Digestive Enzymes Ultra offers a comprehensive blend of vegetarian digestive enzymes to support protein, carbohydrate, fat, fiber and dairy digestion. Suggested use: 2 capsules with each meal.
  • Betaine HCl supports healthy gastric function, promoting the absorption of protein, vitamin B12, calcium and iron from food sources. Suggested use: 1 capsule, 3 times daily, with each meal.


  • MicroDefense w/ Oregano is a combination of plant extracts designed to support healthy gastrointestinal tract function and microbial balance. Suggested use: 1 capsule, 1-3 times daily, just before a meal, with 6-8oz water for 2-3 months.


Functional GI Protocol: This protocol supports abdominal comfort, bloating, occasional diarrhea, constipation or a mix of both.

Drug Nutrient Interactions Checker | DNI Calculator: Offers scientifically supported, clinically relevant information that’s easy to understand with product suggestions based on verifiable science.

You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.


  1. Sperber AD, Bangdiwala SI, Drossman DA, et al. Gastroenterology. 2021;160(1):99-114.e3. doi:10.1053/j.gastro.2020.04.014
  2. Fritz N, Berens S, Dong Y, et al. J Mol Med (Berl). 2022;100(11):1617-1627. doi:10.1007/s00109-022-02244-w
  3. Oka, P., Parr, H., Barberio, B., Black, C. J., Savarino, E. V., & Ford, A. C. (2020). The Lancet Gastroenterology & Hepatology. doi:10.1016/s2468-1253(20)30217-x
  4. Vita AA, Zwickey H, Bradley R. Front Nutr. 2022;9:962093. Published 2022 Sep 6. doi:10.3389/fnut.2022.962093
  5. Awad K, Barmeyer C, Bojarski C, et al. Cells. 2023;12(2):236. Published 2023 Jan 5. doi:10.3390/cells12020236
  6. Zhou Q, Zhang B, Verne GN. Pain. 2009;146(1-2):41-46. doi:10.1016/j.pain.2009.06.017
  7. Singh P, Silvester J, Chen X, et al. United European Gastroenterol J. 2019;7(5):709-715. doi:10.1177/2050640619826419
  8. Guo H, Jiang T, Wang J, Chang Y, Guo H, Zhang W. J Int Med Res. 2012;40(1):204-210. doi:10.1177/147323001204000121
  9. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Gut. 2004;53(10):1459-1464. doi:10.1136/gut.2003.037697
  10. Zar, S., Mincher, L., Benson, M. J., & Kumar, D. Scandinavian Journal of Gastroenterology, 2005. 40(7), 800–807. doi:10.1080/00365520510015593
  11. Peruhova M, Mihova A, Altankova I, Velikova T. Antibodies (Basel). 2022;11(2):23. Published 2022 Mar 29. doi:10.3390/antib11020023
  12. Su Q, Tun HM, Liu Q, et al. Gut Microbes. 2023;15(1):2157697. doi:10.1080/19490976.2022.2157697
  13. Jeffery IB, Das A, O’Herlihy E, et al. Gastroenterology. 2020;158(4):1016-1028.e8. doi:10.1053/j.gastro.2019.11.301
  14. Pozuelo M, Panda S, Santiago A, et al. Sci Rep 5, 12693 (2015). https://doi.org/10.1038/srep12693
  15. Shah A, Talley NJ, Jones M, et al. Am J Gastroenterol. 2020;115(2):190-201. doi:10.14309/ajg.0000000000000504
  16. Villanueva-Millan MJ, Leite G, Wang J, et al. Am J Gastroenterol. 2022;117(12):2055-2066. doi:10.14309/ajg.0000000000001997
  17. Kunkel, D., Basseri, R.J., Makhani, M.D. et al. Dig Dis Sci 56, 1612–1618 (2011). https://doi.org/10.1007/s10620-011-1590-5
  18. Gandhi A, Shah A, Jones MP, et al. Gut Microbes. 2021;13(1):1933313. doi:10.1080/19490976.2021.1933313
  19. Website: Centers for Disease Control and Prevention: Fast Facts About Food Poisoning. https://www.cdc.gov/foodsafety/food-poisoning.html.  Accessed on November 21, 2023.
  20. Klem F, Wadhwa A, Prokop LJ, et al. Gastroenterology. 2017;152(5):1042-1054.e1. doi:10.1053/j.gastro.2016.12.039
  21. Bashashati M, Moossavi S, Cremon C, et al. Neurogastroenterol Motil. 2018;30(1):10.1111/nmo.13192. doi:10.1111/nmo.13192
  22. Robles A, Perez Ingles D, Myneedu K, et al. Neurogastroenterol Motil. 2019;31(12):e13718. doi:10.1111/nmo.13718
  23. Koyyada A. Therapie. 2021;76(1):13-21. doi:10.1016/j.therap.2020.06.019
  24. Fatima R, Aziz M. Achlorhydria. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507793/#
  25. Zhang J, Zhang C, Zhang Q, et al. Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota. BMC Microbiol. 2023;23(1):171. Published 2023 Jun 19. doi:10.1186/s12866-023-02895-w
  26. Saito YA, Zimmerman JM, Harmsen WS, et al. Neurogastroenterol Motil. 2008;20(7):790-797. doi:10.1111/j.1365-2982.2007.1077.x
  27. Saito YA, Petersen GM, Larson JJ, et al. Am J Gastroenterol. 2010;105(4):833-841. doi:10.1038/ajg.2010.116
  28. Kalantar JS, Locke GR 3rd, Zinsmeister AR, Beighley CM, Talley NJ. Gut. 2003;52(12):1703-1707. doi:10.1136/gut.52.12.1703
  29. Zamani M, Alizadeh-Tabari S, Zamani V. Aliment Pharmacol Ther. 2019;50(2):132-143. doi:10.1111/apt.15325
  30. Chang L. Gastroenterology. 2011;140(3):761-765. doi:10.1053/j.gastro.2011.01.032
  31. Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. Nutrients. 2018;10(5):548. Published 2018 Apr 28. doi:10.3390/nu10050548
  32. Website: www.ibssmart.com. Accessed on November 22, 2023.
  33. Morales, W., Rezaie, A., Barlow, G. et al. Dig Dis Sci 64, 3115–3121 (2019). https://doi.org/10.1007/s10620-019-05684-6
  34. Guilarte M, Santos J, de Torres I, et al. Gut. 2007;56(2):203-209. doi:10.1136/gut.2006.100594
  35. Rastgoo S, Ebrahimi-Daryani N, Agah S, et al. Front Nutr. 2021;8:746703. Published 2021 Dec 16. doi:10.3389/fnut.2021.746703
  36. Sasaki E, et al. Luminescence. 2013 Jul- Aug;28(4):442-9.
  37. Song QH, et al. Int J Clin Pharmacol Ther. 2015 May;53(5):372-6.
  38. Lima AA, et al. Clinics (Sao Paulo). 2014;69(4):225-33.
  39. Oguche S, et al. Am J Trop Med Hyg. 2014 Nov;91(5):925-35.
  40. Takeda R, et al. Phytomedicine. 2013 Jul 15;20(10):861-4.
  41. Force M, et al. Phytother. Res. 2000: 14, 213-214.
  42. Bansal V, et. al. Niger Med J. Nov-Dec 2019;60(6):285- 289.
  43. Khin-Maung-U, et. al. Br Med J (Clin Res Ed). 1985 Dec 7;291(6509):1601-5.
  44. Surofchy DD, Frassetto LA, Benet LZ. Pharm Res. 2019;36(11):155. Published 2019 Sep 4. doi:10.1007/s11095-019-2693-5
  45. Yago MR, et al. Mol Pharm. 2013 Nov 4;10(11):4032-7.
  46. Yong Wen, Jun Li, Qing Long, Chao-chi Yue, Bing He, Xue-gui Tang. International Journal of Surgery, 2020. Volume 79. pp 111-19.
  47. Sun JR, Kong CF, Qu XK, Deng C, Lou YN, Jia LQ. Saudi J Gastroenterol. 2020;26(2):66-77. doi:10.4103/sjg.SJG_384_19
  48. Shang X, E FF, Guo KL, et al. Nutrients. 2022;14(12):2482. Published 2022 Jun 15. doi:10.3390/nu14122482
  49. Nagarajan, N., Morden, A., Bischof, D., King, E. A., Kosztowski, M., Wick, E. C., & Stein, E. M. (2015). European Journal of Gastroenterology & Hepatology, 27(9), 1002–1010. doi:10.1097/meg.0000000000000425
  50. Moayyedi P, Andrews CN, MacQueen G, et al. J Can Assoc Gastroenterol. 2019;2(1):6-29. doi:10.1093/jcag/gwy071
  51. Kies C. ACS Symposium Series. 5(214); 61–70.
  52. Natalia S, et al. Nutrients. 2018 May; 10(5): 576.
  53. Riede L, et al. Curr Med Res Opin. 2013 Mar;29(3):251-8.
  54. Canani RB, et al. World J Gastroenterol. 2011 Mar 28;17(12):1519-28.
  55. Krokowicz L, et al. Int J Colorectal Dis. 2014 Mar;29(3):387-93.
  56. Cushing K, et al. Clin Transl Gastroenterol. 2015 Aug 27;6:e108
  57. Exarchopoulou K, Papageorgiou A, Bacopoulou F, et al. EMBnet J. 2021;26:e980. doi:10.14806/ej.26.1.980
  58. Lackner JM, Jaccard J, Keefer L, et al. Gastroenterology. 2018;155(1):47-57. doi:10.1053/j.gastro.2018.03.063
  59. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Am J Gastroenterol. 2011;106(5):915-922. doi:10.1038/ajg.2010.480
  60. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Am J Gastroenterol. 2011;106(5):915-922. doi:10.1038/ajg.2010.480
  61. Shahabi L, Naliboff BD, Shapiro D. Psychol Health Med. 2016;21(2):176-188. doi:10.1080/13548506.2015.1051557
  62. Varjú P, Farkas N, Hegyi P, et al. PLoS One. 2017;12(8):e0182942. Published 2017 Aug 14. doi:10.1371/journal.pone.0182942
  63. Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. Gastroenterology. 2014;146(1):67-75.e5. doi:10.1053/j.gastro.2013.09.046
  64. So D, Loughman A, Staudacher HM. Am J Clin Nutr. 2022;116(4):943-952. doi:10.1093/ajcn/nqac176