by Molly Knudsen, MS, RDN and Noelle Patno, PhD
It’s no secret that digestive conditions, especially chronic conditions, are commonplace. The most recent data from the National Institutes of Health (NIH) estimates that 60 to 70 million people in the United States are affected by some type of digestive disease.1 However, that data is from 2009, and likely, the overall burden of digestive disease is much higher today. The financial burden of gastrointestinal diseases is also substantial. Health care expenditure for digestive diseases totaled $135.9 billion in 2015, with abdominal pain and inflammatory bowel diseases being two of the top five most costly conditions at $10.2 billion and $7.2 billion respectively.2
The high prevalence and overall impact of chronic digestive conditions requires clinicians be equipped with the most relevant, evidence-based nutritional and lifestyle strategies to help patients manage their symptoms and improve their quality of life. Personalized treatments for chronic digestive conditions are specific to the patient and depend on the diagnosis, symptoms, and whether there are any structural abnormalities to the gastrointestinal (GI) tract. A promising approach to treating these conditions includes the use of probiotic therapy.
Patients with chronic digestive conditions may experience symptoms that are often painful and may hinder daily activities by constraining patients to activities or places with easy access to a restroom. In some cases, probiotics may offer a method that can be utilized to alleviate symptoms associated with various digestive conditions. This article will review the available evidence to support probiotic therapies and the role they play as part of a personalized approach to chronic digestive conditions.
What are probiotics and what digestive conditions can they help with?
According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), probiotics are defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”3 Probiotics are identified by genus, species, and strain, and different strains are associated with different health benefits.4 Research shows that probiotics may be beneficial in alleviating some symptoms of these digestive diseases: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and small intestinal bacterial overgrowth (SIBO).
IBS is considered a functional bowel disorder characterized by chronic abdominal pain and altered and irregular bowel movements which may present as diarrhea, constipation, or both.5-6 It is estimated that IBS affects between 25 and 45 million or 12% of people in the United States.7-9 Symptoms associated with this condition can greatly affect a person’s quality of life by impacting their self-image, social ability, confidence, or comfortability while traveling.9 The primary goal for treating IBS is to manage a person’s pain and discomfort. Studies suggesting dysbiosis, or altered intestinal microbiome, may be a root cause factor in the development of IBS have increased the interest and use of probiotics in the management of IBS.10,11 The World Gastroenterology Organization (WGO) provides guidelines for the consumption and use of probiotics and prebiotics for health conditions and states that certain probiotic strains may provide relief from IBS symptoms.12 Several probiotics have been studied in patients suffering from IBS. Specifically the two probiotic strains Lactobacillus plantarum 299v (L. plantarum 299v) and Bifidobacterium infantis 35624 (B. infantis 35624) have strong evidence and multiple studies demonstrating beneficial effects and providing relief from IBS symptoms.13-16
L. plantarum299v: Based on the evidence, L. plantarum299v is one of the probiotics that is recommended by the WGO for the management of IBS symptoms, particularly abdominal pain and bloating with level 2 evidence.12 One of the key studies showing efficacy compared the effects of a four-week supplemental intervention of L. plantarum 299v to a placebo pill in 214 patients with IBS found that the intake of ten billion colony forming units (CFU) of the probiotic significantly reduced the number of abdominal pain episodes.13 In addition, patients’ perception of the efficacy of their treatment during this study was significantly higher in the L. plantarum 299v group compared to placebo. 13 It is important to note, however, this study consisted of IBS patients complaining of only moderate symptoms, presenting primarily with diarrhea.13
B. infantis 35624: In 2017, the WGO listed B. infantis 35624 at a dose of 100 million CFU with level 2 evidence for improving patients’ global assessment of IBS symptoms.12 One study by O’Mahony et al evaluated the efficacy of B. infantis 35624 in symptom management and cytokine profiles in 77 IBS patients.14 Results showed that those receiving the B. infantis 35624 treatment had significantly lower scores for abdominal pain and discomfort compared to the placebo group and had normalized IL-10 and IL-12 (proinflammatory cytokines) ratio by the end of the study, which were abnormal at the beginning of the study.14 This study indicated that the probiotic strain B. infantis 35624 was effective at relieving common IBS symptoms in patients, and, due to the probiotic’s influence on normalizing a proinflammatory cytokine ratio,14 it may also have immune-modulating properties.
A study by Whorwell et al. found that B. infantis 35624 at the dose of 100 million CFU per day was significantly more effective at alleviating a variety of IBS symptoms such as abdominal pain, bloating, and bowel dysfunction, compared to placebo.15 The higher and lower dosing regimens of B. infantis 35624 did not produce results that were significantly different than that of the placebo group. This study only evaluated the probiotic in women.
There is an ongoing debate in the scientific community regarding which probiotics show greater efficacy for IBS. A protocol was published in December 2019 to evaluate the literature regarding the safety and efficacy thus far demonstrated for probiotics in the treatment of IBS.16 Just three months prior to that, a systematic review claimed that eight weeks of treatment with a multi-strain supplement was most effective. 17 However, that review did not require specific diagnostic criteria for IBS, nor did it consider studies that were older than five years and allowed multiple species combinations to be included that did not specify strains.17 Since IBS has multiple subtypes depending on symptoms and can be highly variable for etiology as well, it is a difficult condition to study as a whole.
IBD often presents as diarrhea, abdominal pain and sometimes bleeding with the diagnosis being dependent on endoscopic verification of inflammation in the intestine18 and affects approximately 3 million Americans.19 Research suggests that potential mechanisms of inflammatory responses to existing bacteria in the gut may be targeted by using probiotics.20 The digestive diseases ulcerative colitis (UC) and Crohn’s disease fall under this umbrella, and, similar to IBS, managing the painful and irritating symptoms of these diseases is often the goal of treatment.
UC: UC is a chronic inflammatory disease that affects the lining of the large intestine causing the formation of sores or ulcers.18 UC is characterized by diarrhea, bloody stools, frequency, urgency, abdominal pain and discomfort.21 The WGO states that “certain probiotics have been found to be safe and as effective as conventional therapy in achieving higher response and remission rates in mild to moderately active UC in both adult and pediatric populations.”12 Based on evidence-based guidelines, the WGO recommends two probiotic therapies for adults with UC: Escherichia coli Nissle 1917 (E coli Nissle 1917) and a mixture of eight different strains.12
E coli Nissle 1917: Multiple studies show that the probiotic strain E coli Nissle 1917 can be just as effective as the medication mesalazine to treat UC.21-23 The WGO cites there is strong evidence supporting this probiotic strain use in the maintenance of clinical remission of UC.12 This probiotic strain is associated with maintaining clinical remission of the disease, confirmed by at least two 12-month studies.22, 23 A study of 116 patients in remission compared the effect of the administration of E coli Nissle 1917 to mesalazine in preventing a relapse of UC after receiving oral gentamicin for a week.22 Results showed that the treatment of E coli Nissle 1917 was just as effective as mesalazine in maintaining UC remission in patients. A larger study of 327 patients sought to answer a similar question.23 In a double-blind clinical trial, patients were randomized to either receive E coli Nissle 1917 or mesalazine treatment for 12 months.23 Results showed that there was a significant equivalence between the number of relapses recorded in the two groups, indicating that relapse treatment of UC with E coli Nissle 1917 is just as effective as mesalazine, often considered the gold standard in UC treatment.
Eight species combination: An eight species mixture containing the strains Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium breve and Streptococcus salivarius subsp. Thermophilius has also been studied in reducing the remission of UC, but the WGO cites that the evidence of this probiotic therapy as a level 3.12 However, this therapy may be more beneficial for a different IBD diagnosis: pouchitis. There is level 2 evidence supporting the use of this eight species combination in not only the treatment of active pouchitis, but also in the maintenance of the condition.12
Crohn’s Disease: Crohn’s disease is also an inflammatory condition that, unlike UC, can impact any part of the GI tract with structurally unaffected areas between sections of diseased areas.18 Probiotic therapies and treatments have been unsuccessful in patients with Crohn’s disease. The WGO concludes that there is no evidence to suggest or recommend that probiotics are beneficial in maintaining or in the remission of Crohn’s disease.12 The specific reason for the lack of success of probiotics and Crohn’s disease is not known and poses the question whether it’s related to the disease itself or mechanisms of the diseased GI segments.20
SIBO is defined as “bacterial population in the small intestine exceeding 105 to 106 organisms per milliliter.”24 This overgrowth of bacteria in the small intestine leads to an increase of the production of hydrogen or methane gas, potentially resulting in malnutrition and fatigue.24 SIBO is common in patients with IBS, cirrhosis, and gastroparesis, as well as in people after following a proton-pump inhibitor prescription.19 A meta-analysis and systematic review of the role of probiotics in preventing and treating SIBO was published in the Journal of Clinical Gastroenterology in 2017.25 Specific probiotic strains and doses were not differentiated in this study, therefore studies with different strains and CFU counts were grouped together. Five randomized controlled trials were included in the meta-analysis. Results indicated that patients with SIBO receiving probiotics as part of the treatment plan had significantly higher decontamination rates and reduced abdominal pain compared to patients not receiving any form of probiotics.25 This meta-analysis provides high-level evidence for the general use of probiotics and SIBO. Single-strain probiotic therapy has also shown to be helpful in the management of SIBO. Specifically, the strain Lactobacillus salivarius UCC118 (L. salivarius UCC118) stands out as an effective option for SIBO symptom relief.
L. salivarius UCC118: In a pilot quality improvement study at the Cleveland Clinic Center for Gut Rehabilitation and Transplantation, 29 patients with SIBO were assigned to consume 100 million CFU of L. salivarius UCC118 per day for 90 days in addition to receiving standard therapy for SIBO. The outcome of the study was to determine L. salivarius UCC118 impact on GI symptoms related to SIBO. Patients self-reported the severity of their symptoms of SIBO such as diarrhea, bloating, and flatulence at baseline, 30, 60, and 90 days. Results showed that consumption of this probiotic strain is effective in alleviating symptoms of SIBO and even delayed or prevented the need for antibiotics.26
Limitations to probiotic research
Probiotics for the management and treatment of some chronic digestive conditions appears promising as there are several probiotic strains that have been identified to be beneficial for conditions like IBS and UC. However, there are several limitations to drawing a clear conclusion on which strain is the best, including inconsistencies between studies in design, patient demographics, duration, dose, and strain being studied. There is also no published data comparing all these strains in the same study.
Probiotics and other chronic conditions
The benefits of probiotics also extend beyond the gut. Certain probiotic strains have also been found to be beneficial for other chronic conditions such as overweight and obesity and upper respiratory tract infections.
- Chronic digestive diseases are a major burden in the healthcare system2
- Managing symptoms such as abdominal pain and bloating and maintaining remission/preventing flare-ups of disease is a main focus of treatment
- L. plantarum 299v and infantis 35624 are a couple of specific probiotic strains that may be helpful in the clinical management of IBS symptoms13-16
- E coli Nissle 1917 has shown promise in patients with UC21-23
- Probiotics as part of a SIBO treatment plan may help with decontamination or amelioration of symptoms25,26
Chronic digestive conditions such as IBS, IBD, and SIBO are becoming more prevalent. Health care practitioners should be equipped with the most updated evidence-based nutrition interventions to treat the often uncomfortable symptoms associated with these diseases. Probiotic therapy is one option to help manage their symptoms. There are a lot of choices when deciding what probiotic strain will be most efficacious for different conditions. Evaluating the scientific evidence of a probiotic strain in specific patient populations is essential for making an efficacious recommendation as part of a personalized approach to treating chronic digestive conditions.
- Digestive Diseases Statistics for the United States. NIH.gov. https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases. Accessed October 29, 2019.
- Perry AF et at. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology. 2019;156(1):254-272.
- 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 prebiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514.
- McFarland LV et al. Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis. Front Med. 2018;5.
- Enck P et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016;2:16014.
- Molinder H et al. How individuals with the irritable bowel syndrome describe their own symptoms before formal diagnosis. Ups J Med Sci. 2015;120(4):276-279.
- Lovell RM et al. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(7):712-721.e4.
- US and World Population Clock. https://www.census.gov/popclock/. Accessed December 6, 2019.
- Facts about IBS. https://www.aboutibs.org/what-is-ibs/facts-about-ibs-2.html. Accessed October 29, 2019.
- Principi N et al. Gut dysbiosis and irritable bowel syndrome: the potential role of probiotics. J Infect. 2018;76(2):111-120.
- Zhu S et al. Identification of gut microbiota and metabolites signature in patients with irritable bowel syndrome. Front Cell Infect Microbiol. 2019;9.
- World Gastroenterology Organisation Global Guidelines: probiotics and prebiotics. Worldgastroenterology.org. https://www.worldgastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english. Accessed October 22, 2019.
- Ducrotté P et al. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012;18(30):4012–4018.
- O’Mahony L et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128(3):541-551.
- Whorwell PJ et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. 2006;101(7):1581-1590.
- Yang M et al. Comparative efficacy and safety of probiotics for the treatment of irritable bowel syndrome: a systematic review and network meta-analysis protocol. BMJ Open. 2019;9(12):e027376.
- Dale HF et al. Probiotics in irritable bowel syndrome: an up-to-date systematic review. Nutrients. 2019;11(9).
- Matsuoka K et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53(3):305-353.
- Dahlhamer JM. Prevalence of inflammatory bowel disease among adults aged ≥18 years — United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65.
- Haller D et al. Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome. J Nutr. 2010;140(3):690S-697S.
- Scaldaferri F et al. Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update. World J Gastroenterol. 2016;22(24):5505-5511.
- Rembacken BJ et al. Non-pathogenic Escherichiacoli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. Lancet. 1999;354(9179):635-639.
- Kruis W et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coliNissle 1917 is as effective as with standard mesalazine. Gut. 2004;53(11):1617-1623.
- Dukowicz AC et al. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol.2007;3(2):112-122.
- Zhong et al. Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systematic review of current evidence. J Clin Gastroenterol. 2017;5:300-311.
- Cresci G et al. Effects of Lactobacillus salivarius UCC118 in reducing symptoms of small intestinal bacterial overgrowth [abstract] (2016). (http://journals.sagepub.com/pb-assets/cmscontent/PEN/CNW16_Monday_Poster_Abstracts_revised.pdf)
Molly Knudsen, MS, RDN is a writer at Metagenics. She completed her dietetic training with an emphasis on nutrition education at Texas Christian University and earned a Master of Science in Nutrition Interventions, Communication, and Behavior Change from the Friedman School of Nutrition Science and Policy at Tufts University. Knudsen has experience working with commodity boards and providing student athletes with nutrition coaching. She now practices nutrition education by digesting complex nutrition science through the written word.
Noelle Patno, PhD is the Nutrition Scientist for Digestive Health at Metagenics. Dr. Patno received her PhD in Molecular Metabolism and Nutrition and Masters in Translational Science from the University of Chicago, studying the role of microbial components in intestinal epithelial cell survival related to inflammatory bowel disease. Prior to her graduate studies, Dr. Patno received a chemical engineering degree from Stanford University and worked as an engineer. She has personal experience and interest in preventive nutrition and nutritional therapies for chronic disease, and her current role involves researching and developing probiotics, prebiotics, and other nutritional programs for the promotion of digestive and overall health.