clinical trials

Clinical trial for probiotics in irritable bowel syndrome fails to show efficacy

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting about 10-15% of people in the United States alone, according to the International Foundation for Functional Gastrointestinal Disorders website. Fortunately, as described by the IFFGD, IBS is a functional disorder, meaning that while it does affect quality of life, it does not affect life expectancy. Probiotics have been studied as treatment for IBS because, as we’ve seen in many other examples of probiotic use, it is safe and rarely has any negative effects on the consumer. Some trials have shown that probiotics help relieve the symptoms of IBS; however the conclusions are controversial due to study structure and participant numbers. For this reason, scientists in Seoul, South Korea recently published a study in the Journal of Clinical Biochemistry and Nutrition, which studied the effects of a multi-species probiotic mixture on IBS symptoms using a double-blind study with a large number of participants.

Eighty-one patients participated in the 4-week-long double-blind study, with 42 people receiving a multi-species probiotic (containing Lactobacilli, Bifidobacteria, and Streptococci) and 38 people receiving a placebo. Baseline fecal samples were collected before probiotic/placebo consumption, revealing no significant difference between the two groups of participants. After consumption, the probiotic group showed a significant increase in concentrations of the probiotic bacterial strains in fecal samples, but not significant increase of levels of Bacteroidetes and Firmicutes.

In terms of symptom relief, while the probiotic group reported a greater percentage of relief, it was not significantly greater than the placebo group. This could be a classic case of the placebo effect, which is a phenomenon in which a sham treatment can actually improve symptoms because the person receiving the placebo believes it will help them. The results of this study are not concrete because there was no significant difference in symptom improvement; however there were significant increases in probiotic strains in fecal samples of the probiotic group. This study could be a step in the right direction toward relieving IBS symptoms.

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

New contraceptive vaginal ring does not increase risk of vaginal infections

The Nuvaring, a type of vaginal ring.

The Nuvaring, a type of vaginal ring.

A newly developed contraceptive device that consists of a vaginal ring that is meant to be used for an entire year is currently under development.  As part of this device’s safety trials the scientists who developed the device monitored how it would impact the vaginal microbiome.  The vaginal microbiome is critical to vaginal health, and certain changes to the vaginal flora are associated with bacterial vaginosis (BV), yeast infections, and other vaginal diseases.  Implanting devices will certainly affect the vaginal microbiome, but fortunately, the scientists determined that the device did not increase the likelihood of getting a vaginal microbiome-mediated disease.  They published their results last week in PLoS ONE.

The vaginal microbiomes of 120 women using the device were measured over the course of a year.  There were no significant increase in the rates of BV over the course of the year.  In addition, the levels of Lactobacilli, which are associated with a healthy vagina, and Gardnerella vaginalis, which has been associated with BV, remained relatively unchanged over the course of treatment.  In addition, measurements on the actual surface of the vaginal ring matched the overall vagina quite well in terms of microbial colonization. In both cases, Lactobacilli dominated.

Any fluid or device inserted into the vagina should be considered for its effect on the vaginal microbiome, for example, douching is associated with BV.  Fortunately, this safety study showed that the vaginal ring did not increase rates of disease, so women out there using a vaginal ring for contraception need not be too concerned that their ring is negatively impacting their vaginal health.

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Randomized clinical trial shows probiotic may not be an effective treatment for colic

Many families have experienced colicky infants who have excessive and inconsolable crying.  The cause of this behavior is largely unknown, however it is beginning to be linked to a variety of diseases, including allergies and gastrointestinal disorders.  Many remedies have been suggested to help assuage these infants, including probiotic therapies, but thus far the evidence of their efficacy is unknown.  Researchers in Finland put one of the probiotic therapies, using Lactobacillus rhamnosus GG (LGG), to the test and conducted a double blind randomized clinical trial to discover whether it decreased colic.  They published their results last week in Nature Pediatric Research

The scientists studied 30 colicky infants in the study, who were split evenly into a probiotic group and a control group.  The mothers of the probiotic group orally administered LGG to their children once a day for 28 days, while the mothers of the control group orally administered a placebo.  During this time the mothers kept diaries of how long the child cried, as well as collected stool samples for microbiome testing.  The results showed that the probiotics did not alter the amount of crying for each infant when compared to the placebo group.  In addition there was no statistical difference in the microbiome’s of both groups.

Unfortunately for the families of colicky infants, this study did not show that LGG was an effective colic therapy.  There are other studies that conflict with this one though, so perhaps different types of bacteria, or larger doses could improve efficacy.  The relationship between the microbiome and colic is unclear, however, given the recent advances in gut-brain axis research, we would not be surprised if the two are connected.

 

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Schisandra chinensis fruit modulates microbiome in obese women

Flower from Schisandra chinensis fruit plant

Flower from Schisandra chinensis fruit plant

A search for the blog posts on our site about obesity will result in a list of posts discussing correlations between obesity and bacteria in the gut. People have hypothesized that by modulating the microbiome, you may be able to alter obesity levels in humans. Many studies have looked at how probiotics and prebiotics can modulate bacterial structure to control obesity and metabolic diseases, however little has been done to look at how herbs and fruits could modulate bacterial composition.

A recent study from Korea looked at Schisandra chinensis fruit (SCF), a fruit found most commonly in northern China, that has a long history of being used in East Asian culture as a therapeutic for conditions such as diabetes, obesity, cough, and other conditions.  Previous studies of SCF in mice have shown that it modulates the microbiome, however no human trials had been previously conducted. To analyze this in humans, a clinical trial was conducted in Korea to look at the impact that SCF had on gut bacteria, body composition, and blood chemistry.

At the Dongguk University Ilsan Hospital in Korea, scientists recruited women who were obese (BMI over 25) who met other specific medical conditions. 28 women ended up participating in the study, 13 in the SCF treatment group and 15 in the placebo group. The study participants each took either SCF or placebo twice a day for twelve weeks and blood and fecal samples were taken before and after the treatment as well as a physical examination including heart rate, waist circumference, body weight, and blood pressure.

After twelve weeks, both the placebo and experimental group saw a decrease in waist circumference and fat mass, thought the SCF group saw a greater decrease in fat mass, blood glucose and other parameters. An analysis of the fecal samples before and after the twelve weeks saw greater clustering in the SCF group than the placebo group. At the genus level, there was significant differences between the two groups and the SCF group saw a greater abundance of genus levels (both groups saw similar levels of phyla changes). They saw specific clustering between patients in the SCF group despite dissimilar clustering prior to treatment. This showed that SCF had an influence on gut microbiota that was dependent on gut bacteria prior to treatment.

This study found differences between bacterial composition in patients who were given the Schisandra chinensis fruit and those in the placebo group. Many of the bacteria that saw an increase in the SCF group, including Akkaermansia, Roseburia, Prevotella, Bifidobacterium, and Bacteroides, had shown an association with reduced obesity levels in previous studies. While decreased waist circumference, body mass, and other weight loss parameters were seen in the SCF group, the results were not statistically significant. Much research has been done to look at ways of altering the microbiome and this study shows us that we should continue to investigate the effects of herbs and fruits on our microbiome.  

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Clinical trial suggests dysbiosis may be involved in the progression of acute pancreatitis

The pancreas.  1: Head of pancreas 2: Uncinate process of pancreas 3: Pancreatic notch 4: Body of pancreas 5: Anterior surface of pancreas 6: Inferior surface of pancreas 7: Superior margin of pancreas 8: Anterior margin of pancreas 9: Inferior margin of pancreas 10: Omental tuber 11: Tail of pancreas 12: Duodenum

The pancreas.  1: Head of pancreas 2: Uncinate process of pancreas 3: Pancreatic notch 4: Body of pancreas 5: Anterior surface of pancreas 6: Inferior surface of pancreas 7: Superior margin of pancreas 8: Anterior margin of pancreas 9: Inferior margin of pancreas 10: Omental tuber 11: Tail of pancreas 12: Duodenum

Acute pancreatitis is a sudden and severe inflammation of the pancreas.  It is responsible for many emergency room visits each year, but what causes its onset is unknown.  Most cases are mild, and can be treated with very passive measures, such as fasting or rehydration.  Other cases though (around 25%), are more severe, and require medical interventions, such as surgery.  Recently, researchers in China conducted a clinical trial on people with acute pancreatitis in order to figure out what, if any, connections existed between the microbiome this disease.  They published their results in the journal Pancreas.

The researchers sampled the feces and blood of 76 patients with acute pancreatitis every few days as the disease progressed (44 were severe cases and 32 were mild), along with 32 healthy controls.  They discovered a dramatic decrease in microbiome diversity occurred in those people with pancreatitis, which was characterized by an increase in Enterococcus and a decrease in bifidobacteria compared to controls.  In addition, pro-inflammatory molecules in the blood were directly correlated with the abundance of Enterococcus in these patients.

It is difficult to connect the microbiome to many inflammatory diseases because the mechanisms for how this occurs are still not totally understood.  Hence, many studies, like this one, are only able to show a correlation between the microbiome and these diseases.  Still though, these correlations can be powerful, and at the very least show the need for more research.  So while it may not be true that a dysbiosis causes acute pancreatitis, they are clearly associated.  

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Probiotics may be able to prevent depression

Clinical studies have shown that probiotics can decrease anxiety, improve mental outlook, and induce positive mood changes and outlook.  In fact, some bacteria strains have been shown to reduce anxiety and depression in mice by directly modulating nerve firings associated with these cognitive maladies.  A recent study conducted by Leiden University in The Netherlands explored further in human subjects to assess whether or not probiotics, composed of various strains of Bifidobacteria and Lactobacilli could specifically modulate cognitive reactivity to sad mood, a well-characterized indicator for vulnerability to depression. 

In brief, cognitive reactivity is defined as a series of dysfunctional patterns of thinking prompted by subtle mood changes, such as rumination, aggression, and hopelessness.  It is thought that cognitive reactivity is central in the development, maintenance, and recurrence of depression episodes.  This behavioral reaction is considered to have significant predictive value in detecting vulnerability to developing clinical depression.  Due to this implication, cognitive reactivity is considered a target for therapeutic intervention to prevent depression onset, and was thus analyzed in this study. 

40 healthy, non-depressed adults were selected and split into two groups, each receiving a 4-week regiment of a probiotic or a placebo.  The participants filled out questionnaires before and after the regiment to assess cognitive reactivity and depression symptoms.  Of the several behavioral indicators of cognitive reactivity that were assessed, aggression and rumination were significantly modified according to the behavioral questionnaires.  Specifically, post-regiment scores in the probiotic group were significantly lowered from pre-regiment scores, and this was not observed in the placebo group.  All told, this suggests that a probiotic regiment eased cognitive reactivity to aggressive and ruminative thoughts.

This study is the first to show that probiotics can modulate an important cognitive process that determines vulnerability to clinically diagnosed depression.  These findings are additionally enlightening with respect to the gut microbiome’s role in overall cognitive health.  As is often the case however, there were some limitations.  Specifically, it would have been interesting to investigate biological underpinnings of these interactions in complementary animal models, especially in light of previous findings that indicate probiotics can facilitate microbiota to synthesize and release serotonin.  On Monday we highlighted work done by Professor Diane Hsiao’s group at Cal Tech that stressed the gut microbiome’s role in serotonin production.  As we mentioned, serotonin is implicated in many bodily functions, including a vast range of cognitive mechanisms.  Indeed, serotonin systems have been primary target for therapeutic treatment of depression.  Zoloft, one of the most highly prescribed antidepressants in the world, blocks serotonin metabolism to facilitate its endogenous mode of action in the brain. 

Not only do the current findings complement those from the Cal Tech lab, but they also highlight an exciting new potential toward therapeutic approach.  Conventional therapies that directly target serotonin systems can be ineffective and have many undesired side-effects and limitations.  Understanding the microbiome’s role in serotonin production can give us more insight and perhaps pave a way toward a more organic therapeutic approach aimed at preventing and/or treating depression.  

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.