It's been one year since NEA, in collaboration with four peer patient advocacy organizations, hosted the landmark patient-focused drug development (PFDD) meeting dedicated to eczema.
Published On: Aug 13, 2013
Last Updated On: Aug 13, 2013
Despite their tiny size, bacteria play an important role in eczema and in the overall health of the skin [Hanifin 2009]. Beyond the frequent skin infections associated with severe disease, there is the even more important idea that colonizing bacteria—those that are simply residing on the skin—may also directly drive inflammation [Abeck 1998].
Recent studies have found that in patients with atopic dermatitis (AD) the balance of bacteria on the skin is highly abnormal, with a preponderance of “bad” bacteria such as staphylococcus [Lin 2007]. Reacting to this information, there has been a quiet revolution instituting the use of dilute bleach baths in the hope that this will reduce these unwanted bacteria on the skin and improve skin health and some early research has demonstrated exactly this [Huang 2009].
Indeed, it seems that since the discovery of bacteria in the late 1600s the goal has been to eliminate these seemingly harmful microorganisms living in and on our bodies with an expanding armamentarium of antiseptics and antibiotics. But early in the 20th century, Russian scientist Élie Metchnikoff proposed that some of the bacteria in the human body could be beneficial and act as a natural barrier against disease [Metchnikoff 1908].
The modern conception of this innovative idea is “probiotics.” the National Center for Complementary and Alternative Medicine (NCCAM) defines probiotics as “live microorganisms (e.g., bacteria) that are either the same as or similar to microorganisms found naturally in the human body and may be beneficial to health” [NCCAM 2012].
It turns out that our body is a host to such a multitude of bacteria that the cells of these microorganisms outnumber our own cells by a factor of ten to one [NCCAM 2012]. Collectively, the microorganisms inhabiting our bodies are known as the “microbiome.” Much current research focuses on collecting data about these microbial communities and the sites of the human body where they are found, as well as the implications of microbiome changes on human health.
In 2008, the National Institutes of Health (Nih) launched the Human Microbiome Project: a research collaboration to map, for the first time, the microorganisms that are part of the human body. This massive undertaking aims not only to identify and analyze the diversity of bacteria, but also to measure the impact of the microbiome on a variety of acute and chronic health conditions, from eczema and common respiratory illnesses to obesity, diabetes, and autoimmune conditions such as Crohn’s disease. The big idea is that in addition to—or perhaps instead of—using antibiotics to kill harmful bacteria, probiotics can perhaps be used to restore healthy bacteria to bring the body back into balance.
This brings us to our central question: Can probiotics help treat diseases?
Despite great activity among researchers on the topic of probiotics, data to support their efficacy has been somewhat mixed, and clinical evidence on the use of specific probiotic strains to treat or prevent diseases is limited.
Standard protocols for clinical trials have been lacking and there have been quality control issues. Some of the studies with the most encouraging results focus on the prevention and treatment of gastrointestinal (GI) diseases, specifically traveler’s diarrhea, antibiotic-associated diarrhea, and irritable bowel syndrome.
Several studies support the use of probiotics for prevention and treatment of traveler’s and antibiotic-associated diarrhea, including a review of 82 studies [Hempel 2012] and an overview of probiotic efficacy for GI diseases [Ritchie 2012].
A recent study of multi-strain Bifidobacterium and Lactobacillus probiotic supplementation shows a decrease in symptom severity in patients with IBS [Cui 2012], while a systematic review concludes that only the specific strain of Bifidobacterium infantis (namely, 35624) has shown efficacy for improvement of IBS symptoms [Brenner 2009].
Research also offers promising evidence that probiotics might help to treat childhood respiratory infections, genitourinary infections, as well as atopic dermatitis and allergic diseases.
Based on this clinical evidence, the American Academy of Family Physicians gives the following key recommendations for practice regarding probiotic use:
Probiotic therapy as a treatment for atopic dermatitis has been escalating in recent years. Indeed, considering the increasing prevalence of eczema and the lack of a definitive cure, patients and parents often turn to complementary and alternative medicine treatments when they are dissatisfied with the result of conventional medicine [Astin 1998].
In addition, atopic dermatitis is often associated with other allergic diseases, including food allergies, asthma and seasonal allergies, and some experts advocate the “atopic march” theory, which suggests that atopic dermatitis may lead to subsequent allergic conditions such as those of the respiratory and gastrointestinal systems. Therefore, there is significant interest in the prevention of atopic dermatitis to possibly halt the development of other allergic illnesses [Spergel 2010].
Given that the bacterial flora is very different in patients with atopic dermatitis, the idea that adding back healthy bacteria might be a useful treatment is compelling. An exciting paper in 2001 showed that the probiotic strain Lactobacillus rhamnosus GG reduced the incidence of atopic dermatitis in at-risk infants through the age of 7 years [Alliomaki 2001].
In 2005, a similarly exciting paper seemed to take this a step farther, showing that probiotics given twice daily to children with moderate to severe AD led to significant improvements over the use of a placebo [Weston 2005].
At that time there was a lot of initial excitement about the positive role of probiotics in eczema prevention and treatment. Then in 2008, a study found no reduction in incidence or severity of atopic dermatitis with probiotic supplementation, and it even found an association between such supplementation and increased incidence of wheezing bronchitis [Kopp 2008]. In this study, however, only breastfeeding mothers were supplemented with the Lactobacillus rhamnosus GG strain of probiotics during the first three months after birth.
In the studies that followed, researchers experimented with different strains of probiotics, dosing, timing, and frequency in order to optimize the efficacy of probiotics and achieve more consistent results. In 2009, in the first study of its kind, the Probiotics and Allergy (PandA) trial selected strains of probiotics based on their anti-inflammatory activity [Niers 2009].
Trial participants received either a multistrain probiotic supplement (Bifidobacterium bifidum, Bifidobacterium lactis, and Lactococcus lactis) or a placebo administered prenatally (6 to 8 weeks prior to delivery) and postnatally (infants were supplemented for 12 months).
Fecal colonization with Bifidobacterium was confirmed in 100 percent of the probiotic group at three months of age, while only 85 percent of the control group showed such colonization. A larger proportion of the probiotic group also demonstrated colonization with Lactococcus lactis. Blood analysis to measure the levels of inflammatory markers revealed lower levels in the probiotic group, suggesting some anti-inflammatory effect.
The physician-reported incidence of eczema in the trial was 23 percent in the control group and 6 percent in the probiotic group, which was significant. The results also showed a long-term reduction in the incidence of eczema measured at 2 years of age.
Supporting this work, a meta-analysis of 14 trials demonstrated that probiotics decreased the incidence of atopic dermatitis, regardless of prenatal or postnatal use or the subjects receiving the probiotics (mother or child) [Pelucchi 2012]. Additionally, in a 2012 review, a significant risk reduction was found for AD in children 2 to 7 years old after the administration of Lactobacilli strains of probiotics during pregnancy [Doege 2012].
A very recent study on probiotics and AD prevention, published October 2012 in The Journal of Allergy and Clinical Immunology, found that supplementation with strains of Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum in combination reduced the risk of developing eczema in infants [Rautava 2012]. In this study of 241 mother-infant pairs, breastfeeding mothers were supplemented with probiotics beginning 2 months before delivery and during the first 2 months of breast feeding. Reduction in eczema development in high-risk infants was confirmed up to 2 years of age.
Research focused on using probiotics for the treatment of established eczema, on the other hand, has not yielded such promising results. A 2008 review of 12 trials found no differences in outcomes related to the use of probiotics and placebos, with a small increased risk of adverse effects, such as infections and bowel ischemia, among those using probiotics [Boyle 2008]. A more recent review of clinical evidence for probiotic use in the treatment of eczema did not find convincing evidence to recommend the use of probiotics for that purpose [Van der Aa 2010].
In light of these mixed and frankly confusing results, many questions remain, including: What is the best timing for probiotic therapy? What are the ideal strains of bacteria to use? What is the best dosage? And, is there a particular patient type who will benefit the most from probiotic supplementation?
It seems that high doses (3-50 billion CFu/d) of Lactobacillus rhamnosus, Bifidobacterium lactis and Lactobacillus acidophilus probiotics in single or multi-strain formulations currently hold the most promise for prevention and treatment of eczema, but more studies evaluating single and multiple strain probiotics and exact dosing are needed to confirm most beneficial bacterial species.
Further complicating matters, in the United States probiotics are regulated as dietary supplements and therefore are not required to adhere to quality control measures ensuring the purity, potency, and safety of these products.
Although most commercially available probiotic strains are generally regarded as safe, there may be an increased risk of negative side effects in immunocompromised populations. There are case reports of Lactobacillus sepsis (blood infection) directly linked to probiotic supplementation in older adults with chronic diseases and in premature infants; however the source of infections has not been conclusively proven [Boyle 2006].
A 2011 review of the safety of probiotics performed by the Agency for Healthcare Research and Quality concluded that the current evidence does not suggest a widespread risk of adverse side effects associated with probiotics. However, the data on long-term safety is lacking, and the risk of serious adverse reactions may be greater in special populations [Boyle 2006].
Despite their promise, probiotic use for both eczema prevention and treatment is still clouded by many questions, but it is possible that, as more data is uncovered, the answers will become clear, and we may yet be able to harness these helpful bacteria to heal the skin.