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The intestinal mucosa has an extensive surface area (>300m2) that provides a physical and immunological barrier to infection. The physical barrier includes the mucous layer, the epithelial cells and the tight junctions between these cells. It acts as a structural separation between the lumen of the gastrointestinal tract (essentially part of the external environment) and the internal environment. The immunological barrier is part of the mucosal-associated lymphoid tissue (MALT) and is termed gut-associated lymphoid tissue (GALT). GALT contains one of the largest pools of immunocompetent cells in the body, with over 60- 80% of total immunoglobulins circulating at some point in their life through this tissue. GALT also has more than 106 lymphocytes/g tissue, making it a more concentrated source of lymphocytes than all of the other immune organs combined. The GALT can be separated into organized lymphoid tissue and diffuse lymphoid tissue. Organized lymphoid tissue includes mesenteric lymph nodes and Peyer’s patches, containing microfold (M) cells, dendritic cells (DC) and B cells. Dendritic cells are antigen-presenting cells (APC) that sample antigen, process it, modify it and present it to other immune cells, like naïve T cells, to initiate specific immune functions. Diffuse lymphoid tissue is found primarily in the connective tissue of the lamina propria of the gastrointestinal tract layers.

It contains lymphocytes like CD4+ T cells in the lamina propria, CD8+ T cells between the epithelial cells (intraepithelial lymphocytes (IEL)), B lymphocytes (memory and plasma cells that produce type A immunoglobins (IgA)), and natural killer (NK) cells. The intestinal mucosal barrier is a highly selective, intelligent system that protects us from pathogens.6 It must selectively exclude potentially toxic and infectious material from entering systemic circulation. It also must tolerate commensal bacteria and beneficial nutrients. Hypo-responsiveness towards ingested substances is the predominate response of the GALT. This response is termed oral tolerance and can be both T- and B- cell mediated. Normally, oral tolerance prevents an immunogenic response, but if suboptimal oral tolerance is present, hypersensitivity responses to oral antigens can occur. For example, if a person does not tolerate milk proteins, a hypersensitivity reaction to dairy products can occur.(6) This hypersensitivity response often begins with either Th1 or Th2 cell polarization.

Commensal bacteria in the gastrointestinal tract play an integral role in both innate and humoral immunity. It is well established that this protective role can be maintained or modulated by the ingestion of probiotics. More recently, it has been shown that specific probiotic strains can influence the secretion of cytokines to help direct naïve helper T cells towards either a Th1 dominant, cell-mediated immune response or towards a Th2 dominant, humoral immune response. This paper will review current knowledge of the Th1: Th2: Th3/ Treg model of humoral immunity as well as introduce how strain-specific probiotics can be used therapeutically to help balance this immune response and therefore, help prevent and treat disease.

It is now well established that commensal intestinal microflora influence the physiology and pathology of the host. Moreover, it has been shown that the microbiological content of the gastrointestinal tract can be altered by the oral administration of health promoting microorganisms, namely probiotics. As a result, there is increased interest in the role of probiotics in maintaining optimal human health by preventing and treating disease. Probiotics are defined as living microorganisms that, upon ingestion in sufficient numbers, exert health benefits beyond basic nutrition.(1) Probiotic bacteria, like certain Lactobacillus and Bifidobacterium species, influence human health in a number of different ways.
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One of the most accepted and researched effects of supplementation with probiotics is immune system modulation. Probiotics influence several components of an immune response including humoral, cellular or innate immunity. A specific component of the humoral immune response involves the secretion of specific cytokines to influence naïve T-helper (Th) cells to become either Th1 or Th2 dominant and therefore, promote cellular or humoral immunity, respectively. Probiotics can help influence the release of specific cytokines by unique T cell subsets and therefore, play a fundamental role in mucosal immunity. In a healthy immune system, there is a balance between Th1 and Th2 cell activity. This balance is transiently shifted when necessary to support cell-mediated immunity or humoral immunity but usually is rebalanced quickly once the specific immune challenge is removed. However, if a cytokine imbalance persists, a specific T-cell pathway is maintained and immunopathological diseases like atopy, hypersensitivity reactions and chronic inflammation can occur. A recent hypothesis, termed the hygiene hypothesis, postulates that the increased prevalence of allergy in industrialized nations is due to inadequate microbial stimulation and therefore, development of a robust Th-1 response during childhood. This poorly developed Th-1 response occurs because of excessive hygiene, intensive food sterilization and modification of commensal gut flora in newborns from persistent feeding with artificial formulas. Without adequate feedback from Th-1 cell dependent cytokines, Th-2 cell dependent cytokines, like IL-4, IL-5, IL-9 and IL-13, predominate to promote the development of the allergic response.
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It recently has been observed that specific probiotic strains stimulate the secretion of specific cytokines and, therefore, facilitate the development of naïve T-cells towards a particular immune pathway. This paper, which is part of the proceedings of a symposium, will summarize the Th1/Th2 model of the immune system, the cytokines that regulate T cell development and the effects of specific probiotic strains on the modulation of mucosal immunity. An enhanced understanding of how specific strains of bacteria influence the immune system can be useful in selecting probiotics that can help correct the imbalances postulated by the hygiene hypothesis. Restoring the balance between Th-1 and Th-2 cells would help prevent and treat many diseases.

Naturopaths, if they wish to be included in an integrated-healthcare system, would be wise to take an active role and contribute to the framework of data that will be common in the near future. Initiatives are arising for naturopathic doctors to be included in health information exchanges. Again, the voices of naturopaths can be significant in influencing policy, as they have been in contributing to the new strategic plan of the National Institutes of Health’s National Center for Complementary and Alternative Medicine in its renewed focus on discipline-specific research. This is an essential development for the study of naturopathic medicine per se, rather than its components. The primary-care provider (PCP) shortage also favors the potential of naturopaths, as they are the licensed complementary and alternative medicine (CAM) professionals who may be the readiest for integration as PCPs. Technological change—with practice and patient-specific data collection abilities in office with electronic health records (EHR) and via the Internet—is stimulating these initiatives. Adoption of EHRs among naturopaths is nearly keeping pace with that in independent conventional practice, and the academic clinics are making good progress on implementation.

The collaborations resulting in the Naturopathic Medical Research Agenda 2002–2005 and the Naturopathic Physicians Research Network were solid steps forward for joint naturopathic research action. From about 1985, the profession began to do its own research; in the 1990s, we gained experience and academic research departments grew. In the last decade, we clarified the right research questions and the general methodologies, while a growing number of naturopathic physicians have been trained at research universities across the country. Now it is time to build upon these gains and produce the studies and data that can help transform the profession.

The Naturopathic Physicians Research Institute (NPRI) is a nonprofit organization established in 2010 and led by naturopathic scientists and clinicians. Its mission is to “stimulate, organize, fund, conduct and disseminate research on the clinical practice and outcomes of naturopathic physicians in order to improve practice and the health of our patients and communities.” The NPRI is the home of the Naturopathic Physicians Research Network, now with more than 100 members in the United States and Canada and registered as a primary-care research network with the US Agency for Healthcare Research and Quality. For more information about the NPRI, visit their website. To become a member of the Naturopathic Physicians Research Network, simply complete this registration form.

If you are a leader in a naturopathic academic institution, profession association, naturopathic specialty society, or in the industries involved in naturopathic care, or if you are a potential or established naturopathic scientist, please join us at this groundbreaking event and help create the firmest foundations for the profession’s future.

The first naturopathic Science Summit focusing on health policy will be held on August 16, the day before the American Association of Naturopathic Physicians Annual Convention (AANP) at the Arizona Biltmore in Phoenix. The Science Summit will bring together naturopathic clinicians, researchers, and leaders of academic and professional associations, as well as industry, to address the profession’s impact on health policy and policy-makers—public and corporate—and the role research plays in supporting policy-changing efforts. Ian Coulter, PhD, senior health policy analyst at the RAND Corporation, will provide the keynote and participate in discussions.

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During the day-long event, we will explore how the AANP mission, naturopathic research, and evidence-informed health policy can be aligned for healthier patients, a more effective healthcare system, and a flourishing profession. Most importantly, we will attempt to define directions that will provide the most important data for 1) regulation for patient access and safety, 2) public and private health program inclusion, and 3) practice improvement. The importance of the Science Summit to all the whole profession calls for its broad sponsorship by the AANP, the Association of Accredited Naturopathic Medical Colleges, and the Naturopathic Physicians Research Institute (NPRI).

Naturopathic physicians are maturing as a profession. Their voices carry weight well beyond their numbers in complementary and alternative disciplines and research, as well as in public media. The profession is more ready than ever to reveal patient results in a way that can impact government and corporate policy, whether for licensing in additional states and provinces, greater access under public and private insurance plans, or simply greater intellectual authority in the control of its own growth and practice development. A cadre of scientists and health researchers within the profession have developed the skills and infrastructure to respond to research and assessment needs. The development of a health policy center at Bastyr University concomitant to its initiation of web-based data collection and outcomes systems is reflective of both understanding and capacity for sophisticated work. The series of studies of whole-practice naturopathic care from the Canadian College of Naturopathic Medicine, including cost assessment, in the last few years are the progenitors of the kinds of studies that should be supported.

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The policy environment is also ready to be influenced by the real-world results of naturopathic physicians, making careful and conscious professional activity in outcomes and cost assessment more opportune than ever. The health crisis has every federal and state agency seeking answers to restraining costs while responding to epidemics of chronic disease and an aging population. Health reform is bringing with it mandates for reporting as a condition of participation.

There are convincing initial studies with animal models and humans to demonstrate that probiotics can reduce Th1 or Th2 skewed disorders, like gastrointestinal inflammation and allergic diseases. These initial studies are encouraging but future studies must be conducted to more clearly determine the impact that specific probiotic strains have on T cells and immunopathology. Further studies also are needed to determine the therapeutic dose and timing of probiotic administration needed to produce these immune responses in humans.

This increased knowledge of the effect of specific strains of probiotics on immune-system modulation has widespread medical implications. For example, when a patient has a Th1-cell dominant disorder, such as Crohn’s disease, then administration of specific probiotic strains can be given to promote secretion of IL-10 and TGF-β cytokines and, therefore, down-regulate chronic Th1 cell-associated inflammation and promote a return to balanced immunity.

Alternately, if a person has a Th2 cell dominant disorder, like allergies, specific probiotic strains can be given to help release TGF-β, reduce IL-4 and IL-5 or increase IL-12 and, therefore, shift the immune system back to a balanced Th1:Th2 response.

An increased understanding of the unique effects of strain-specific probiotics on the immune system will help healthcare professionals be more specific with their therapeutic intent and select certain probiotic supplements based on the diagnosed condition and the desired direction needed to positively influence the immune system. Nutraceutical companies also can formulate safe, effective probiotic supplements with unique effects on the immune system that can be more effectively used to reduce pathogenesis and maintain intestinal homeostasis. Currently, there are some multistrain probiotics that are known to affect Th1- or Th2-cell associated immunity. For example, NFH ProBio SAP-90 contains a blend of probiotic strains that will cause a more balanced Th1:Th2 response, whereas HMF forte more specifically activates the Th1 pathway and thus down-regulates overactive Th2 disorders. Conversely, the probiotic mixture VSL#3 promotes secretion of cytokines that drive a Th2 response and, therefore, will prevent and treat diseases associated with Th1 cell rigidity. With future clinical trials, there will be an increased understanding of how probiotic strains can regulate the production of T cell cytokines to produce a balanced T helper cell response (Th1=Th2=Th3/Tr1) and prevent imbalance (Th1>Th2 or Th2>Th1). Ideally, a more selective choice of probiotics by healthcare professionals can be used to prevent and treat certain immunopathologies and, therefore, maintain optimal health.

The Th2 cell pathway supports humoral immunity by activating specific B cells and promoting antibody class switching. Th2 cells release the cytokines IL-4, IL-13, IL-5 and IL-10 that activate antibody formation or release from immune cells like B cells, mast cells or eosinophils. Persistent, uncontrolled Th2 activation is associated with diseases like atopy (including allergies, eczema, asthma, and allergic rhinitis), chronic fatigue and immunodeficiency syndrome, eosinophilic rhinosinusitis, ulcerative colitis and possibly certain cancers.

Many studies in the past decade have shown that specific probiotic strains can benefit allergic diseases characterized by this chronic expression of Th2 cell-related cytokines. For example, Pochard et al. (2002) in an in vitro study demonstrated that different Lactobacillus strains reduce IL-4 levels (a Th2 cytokine) and enhance production of Th2 cell-related cytokines, supporting a more balanced Th1/ Th2 response.11 More specifically, a three-hour incubation of L. plantarum, L. lactis, L. casei and L. rhamnosus GG (at a concentration of ten bacteria per purified CD4+T cell) inhibited the production of IL-4 and IL-5 in a dose-dependent manner from human polymorphonuclear cells and stimulated the production of the pro Th1 cell cytokines, IFN-γ and IL- 12. In the same experiment, no significant inhibition of IL-4 and IL-5 secretion occurred when the cells were incubated with Escherichia coli TG1, demonstrating that the inhibition of cytokine secretion was specific to certain bacterial strains. It was postulated that supplementation with these specific Lactobacillus strains could benefit patients with allergic diseases by reducing Th2 cytokine production.

Other studies have shown that L. rhamnosus GG can reduce allergic disease symptoms in humans. Ingestion of therapeutic levels of L. rhamnosus GG by breast-feeding mothers and newborn babies resulted in a 50% inhibition of the risk of developing atopic eczema in babies.12,13 These studies provide an example of how administration of strainspecific probiotics can modulate the immune response and down-regulate the Th2 dominance associated with the development of allergies.

Regulatory T cells

There are other subsets of T cells, termed type 1 T regulatory cells (Treg) or Type 3 T regulatory cells (Th3) that help regulate T-helper cell functions and maintain intestinal homeostasis. For example, Treg cells predominantly secret IL-10, a cytokine that down-regulates Th1 activity and, therefore, reduces Th1-associated inflammation. Adequately primed Th3 cells primarily secrete TGF-β, which helps modulate both Th1 and Th2 activity7 (see figure 1). There is increased understanding that Treg and Th3 cells are influential in the maintenance of mucosal immunity and, therefore, the prevention of pathology. Furthermore, certain probiotic strains can moderate these regulatory responses. For example, L. paracasei (NCC2461) stimulates in vitro regulatory T cells to produce TGF-beta and IL-10, cytokines implicated in the oral tolerance response to bovine betalactoglobulin in mice.14,15 Artificial induction of the oral tolerance response, via the administration of strain-specific probiotics, would help modulate hypersensitivity reactions.

The Th1 cell pathway supports cell-mediated immunity, preventing disease from intracellular pathogens like viruses, certain bacteria, yeast, fungi and protozoans. Th1 cellassociated immunity also has a major role in preventing tumor cell development. However, if naïve T cells are chronically Th1 polarized, an overactive cell-mediated immune response can result. For example, persistently high secretion of IL-12 will cause Th1 cells to produce large amounts of pro-inflammatory cytokines like IFN-γ and TNF-α. These cytokines further activate macrophages to produce additional pro-inflammatory mediators (i.e. IL- 12 and IL-18) in a positive feedback loop that has potential pathological consequences (see figure 1).
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Persistent Th1-mediated inflammation of the gastrointestinal tract is associated with pathologies like Crohn’s disease,3 H. pylori gastritis, cellular autoimmunity, chronic recurrent inflammation and possibly rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This Th1 rigidity and the potential pathological consequences can be moderated by upregulating the production of Th2 dominant cytokines, like IL- 4, IL-10 and IL-13. These cytokines inhibit the development of Th1 cells and macrophage activation and, therefore, can prevent inflammatory tissue damage resulting from an overabundance of Th1 cell stimulation.(8) Furthermore, the immunosuppressive cytokines IL-10 and TGF-β, released by regulatory T cells, also down-regulate Th1 rigidity and help control colitis and other inflammatory diseases.(9) Certain probiotic strains can help down-regulate these Th1 dominant disorders and return balance to the immune response. For example, TNF-α plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease, a disease associated with Th1 polarization. Borruel et al. (2002) studied the effect of probiotic bacteria on TNF-α production by obtaining ileal specimens from ten patients with Crohn’s disease. They observed a significant reduction in the production of TNF-α by inflamed Crohn’s disease mucosa when cultured with L. casei or L. bulgaricus, but not with L. crispatus or E. coli.(10) The authors concluded that these probiotic strains had the ability to attenuate the release of the pro-inflammatory cytokines that promote Th1 rigidity by interacting with the intestinal mucosal immunocompetent cells.

Furthermore, in mouse studies it was found that a probiotic mixture of nine different bacterial strains ameliorated recurrent Th1-mediated murine colitis by inducing IL-10 secretion and promoting development of IL-10 dependent TGF-β bearing regulatory cells. Daily administration of 2 mg (approximately 3 billion bacteria) of this probiotic mixture for three weeks to mice during a remission period induced an immunoregulatory response involving TGF-β secreting cells and, therefore, resulted in a milder form of recurrent colitis. These two studies support the therapeutic use of certain strains of probiotics in different animal species to prevent and moderate diseases associated with chronic Th1 cell dominance.

The initial step in the polarization of naive T cells is the interaction of APCs, mostly DCs, with a non-self or “danger signaling” antigen. The physical nature of the antigen and the cytokines subsequently released by the APC encountering this antigen determines whether a Th1 or Th2 skewed immune response occurs. For example, when APCs are challenged with intracellular pathogens, like viruses, a common cytokine secreted is IL-12. This cytokine promotes the differentiation of naive T cells into Th1 cells. Maturing Th1 cells then produce the cytokine IFN-γ, which feeds back in an autocrine loop to trigger the development of more APCs as well as further promote the maturation of naïve T cells into Th1 cells. Additional cytokines, like IL-18, also can be secreted to further influence Th1 development by enhancing IL-12 dependent Th1 cell differentiation and effector function. This self-perpetuating cycle of Th1 dominant cytokines persists until the immune challenge is sufficiently reduced.

If APCs are challenged with blood-borne pathogens, cytokines like IL-4 are released to promote Th2 cell differentiation. Additional cytokines like IL-13 also are secreted under certain conditions, and further promote Th2 polarization and development in an IL-4 independent manner. Maturing Th2 cells continue to release IL-4, generating an autocrine feedback loop that further increases the differentiation of naïve T cells to Th2 cells. Th2 cell dominant cytokines are continuously secreted until the blood-borne pathogens are removed or sufficiently reduced. When naïve T cells become Th1 or Th2 polarized they are committed to that specific pathway and cannot be reversed. Cytokines secreted by Th2 cells activate specific B cells for antigen clearance as well as for antibody class switching. Cytokines secreted by the Th1 cells primarily promote inflammation and the activation of cytotoxic T cells. These Th1 and Th2 specific cytokines interact with each other to antagonize their respective maturation and actions. For example, Th1 cells secrete IFN-γ which inhibits proliferation of Th2 cells, whereas Th2 cells secrete the cytokine IL-4 that prevents Th1 cell differentiation. Further regulation of Th1 and Th2 cells occurs with additional subsets of T cells, termed regulatory T cells (Treg) or Th3 cells. Specific regulation of T cells by Th1, Th2 or Treg/Th3 cells will be discussed in the next sections.

The four-day event (May 20–23, 2010) provided a wide range of information to an audience of healthcare professionals from 21 different countries. The large international interest may be indicative of a growing global interest in functional medicine and innovative thinking surrounding integrative oncology.

During her presentation, Mary Hardy, MD, medical director for the Simms/Mann–UCLA Center for Integrative Oncology, told the audience that patients with cancer visit the doctor twice as often as other patients. She explained that the primary care physician (PCP) often takes a step back during cancer treatment; however, there is a need for PCPs to step forward and play a more active role with their cancer patients.

Hardy, who was on the development panel for the symposium said, “Our goal was to empower IFM/IM primary care physicians to do the things they already know how to do well. This will give the cancer patient the best blend of conventional and complementary care leading to the best outcomes and least toxicity.”

The focus of the symposium was to view cancer as a chronic disease and then address issues associated with the care and healing from this illness. Some key topics included

• oncogenetic expression;
• genetics, epigenetics, and environment;
• antioxidants;
• confusion about vitamin D;
• diet and lifestyle;
• offsetting side effects of conventional treatments; and
• enhancing conventional treatments via an integrative approach.

This is the first time that the Institute for Functional Medicine tackled the issue of cancer care in one of its symposia. “This conference really brought together some of the best clinical practitioners in integrative oncology,” said Tina Kaczor, ND, FABNO, senior medical editor of the Natural Medicine Journal, who also attended the symposium.

“I was pleased to see that several of my colleagues who are Fellows of the American Board of Naturopathic Oncology— specifically Lise Alschuler, Tim Birdsall, Paul Reilly, and Dan Rubin—were speakers at this event,” said Kaczor. “I think naturopathic oncology has a lot to offer in terms of focusing on the patient and using natural agents that benefit our patients throughout their course of treatment. Our education makes us uniquely positioned to understand and integrate various modalities to improve each patient’s quality of life, as well as affect their risk of recurrence.”

Each morning of the symposium Bland provided a synthesis of the information presented the day before. This snapshot not only added Bland’s perspective to the various topics, it also neatly encapsulated points of interest and appeared to be well received by the audience. “This was the class I wish I had available to me years ago when I was struggling to learn how to support cancer patients,” Hardy concluded.

One of the highlights of the symposium was the presentation of the Linus and Eva Helen Pauling award to Dean Ornish, MD, who was also a presenter at the symposium. “Dean Ornish was the first to see that treating the underlying metabolic and nutritional causes of disease was more powerful than conventional medical and surgical approaches to chronic disease,” explained Mark Hyman, MD, who presented Ornish with the award. “Receiving the 2010 Linus Pauling Award is recognition of his seminal contribution to the field of nutritional and functional medicine.”

The United States Census Bureau projects that between 2000 and 2030 the number of Americans 65 years old or older will double. The aging of our population, combined with many other factors, will likely contribute to a corresponding increase in serious illnesses such as cancer. In fact, it is now estimated that 1 in 2 men and 1 in 3 women will develop cancer in a lifetime. Concurrently, an increasingly high number of individuals are living beyond their prognosis. In 2007, more than 11.7 million people were living with a history of cancer.

Cancer continues to put a strain on our healthcare system, not only in terms of increasing prevalence but also increasing costs per individual. A recent report published online in the journal Cancer indicated that the cost to treat cancer has nearly doubled in the past 20 years.

Additionally, if we remain on this course, the number of people diagnosed with cancer will soon far outweigh the number of oncologists available to treat them. Additionally, if we remain on this course, the number of people diagnosed with cancer will soon far outweigh the number of oncologists available to treat them. Data from Erickson and colleagues published in 2007 pointed to a projected shortage of more than 4,000 oncologists by the year 2020.5 The conclusion based on the data was that “a multi-faceted strategy will be needed to ensure that Americans have access to oncology services in 2020. … Among the options to consider are increasing the number of oncology fellowship positions, increasing use of non-physician clinicians, increasing the role of primary care physicians in the care of patients in remission, and redesigning service delivery.”

Primary care physicians may be able to fill some of the gaps now emerging in cancer care. Primary care physicians can help manage side effects and after effects of conventional treatment, counsel patients on diet, and provide practical lifestyle advice that can enhance survivorship and help prevent a recurrence. As it turns out, the increasing prevalence of cancer as a chronic disease provides an increasing opportunity for the primary care physician. This could also be good news for the patient. For example, preliminary research shows that utilization of primary care in the early phase of lung cancer treatment reduced mortality risk.

The 17th International Symposium on Functional Medicine was designed to engage the primary care community in integrative cancer treatment. In his opening presentation, Jeffrey Bland, PhD, FACN, CNS, who founded the Institute for Functional Medicine with his wife Susan, asked the question “How can we deliver better care to our patients?” To a sell-out crowd of doctors, nurses, and other healthcare professionals, featuring a large number of primary care providers, Bland and the other expert presenters attempted to teach how functional medicine can play a role in cancer care. “We need to look at the soil in which these oncogenes can grow,” says Bland. “For many patients, cancer has become a chronic disease that demands long-term management.”

Study Medication and Dosage
Infants were randomly assigned to receive either L. reuteri DSM 17938 [10(8) CFU] or placebo daily for 3 weeks. Parental questionnaires monitored daily crying time and adverse effects. Stool samples were collected for microbiologic analysis.

Key Findings
Those taking L. reuteri experienced a significant decrease in daily crying time. Stool microbiology revealed an increase in lactobacilli and decrease in Escherichia coli in the treatment group. L. reuteri was well tolerated and no adverse effects were noted.

Breastfeeding may serve as an equally powerful treatment, since it improves the microbial milieu of the gut.

Practice Implications
It is well known in the naturopathic field that probiotics address many gastrointestinal conditions effectively, even as a monotherapy. The same authors conducted a similar study in 2007, which found that a related probiotic strain, L. reuteri ATCC 77530, resulted in a decrease in colic symptoms in 95% of the treatment group vs. 7% in the control group.1 Critics of that study point out that it was unblinded, and controls were treated with simethicone.2 Therefore, blinding both groups in this study and removing interfering medications adds strength and significance. The mechanisms behind probiotics’ benefits are not fully understood. However, there are some clues in the literature: Savino and colleagues state that probiotics may improve gut motility and function and decrease visceral pain. Additionally, other research has shown that altered fecal microflora is found in infants with colic, and those children are found to have elevated levels of calprotectin in their stools. Interestingly calprotectin is a marker of intestinal inflammation and possibly increased intestinal permeability and can serve as a predictor of irritable bowel disease later in life. Breastfeeding may serve as an equally powerful treatment, since it improves the microbial milieu of the gut. This explains why a review of 79 articles shows babies who are breastfed have a decreased risk of irritable bowel disease development later in life. At this time, there is no general consensus on the most effective probiotic strains for the treatment of colic. Additional strains that have shown efficacy in colic include Bifidobacterium lactis and Streptococcus Thermophilus.10 It is quite likely that other strains also have benefit, warranting further research in this area.