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.

Microbiome differences between healthy people and those with IBS

Methane (above) is produced by Methanogens, which are increased in the guts of healthy individuals compared to those with diarrheal IBS.

IBS affects somewhere around 11% of all humans.  It is not known exactly what causes the disease but it is characterized by a low grade inflammation in the colon which can manifest itself as cramping, bloating, diarrhea, constipation, and overall abdominal discomfort.  Many scientists now believe this is a microbiome mediated disease that is caused by some sort of dysbiosis in the gut, unfortunately efforts to characterize exactly what differences occur in IBS individuals have not been successful.  A new article published last week in Nature Scientific Reports describes newly discovered differences in butyrate and methane producing bacteria in the guts of people with IBS.

The scientists sequenced the microbiomes of 66 healthy controls and 113 folks with IBS, at two time points 1 month apart.  They discovered that IBS patients had higher amounts of Bacteroides and lower levels of Firmicutes than healthy individuals, as well as an overall lower microbiome diversity.  In addition, there were no major changes to either group’s microbiomes over the one month measurement window.  Interestingly those people with diarrheal IBS had much lower levels of methanogens than healthy controls, and those people with constipation IBS had higher levels of methanogens than healthy controls.  Methanogens convert hydrogen gas to methane in the gut, and this study revealed a link between methane production and gastrointestinal (GI) transit time.  Finally, the researchers determined that diarrheal IBS patients also had much lower levels of known butyrate producers.  Butyrate, a short chained fatty acid (SCFA), is associated with improved GI permeability and overall GI health.

This study described a few important insights in IBS and the microbiome.  These insights, such as the metabolic differences between bacteria in healthy individuals and those with IBS may be important to future therapeutics to treat this disease.  For example, perhaps folks with IBS could eat a lot of fiber and in the hopes of increasing the amount of butyrate in their guts.  Of course, the observed difference is only an association at this point, but other studies have suggested an increase in fiber can help relieve symptoms of the disease. 

Specific mushroom alters microbiome of mice to reduce obesity

Natural medicinal products are used around the world and prominently in Eastern civilizations. One such product, the Ganoderma lucidum mushroom has been used for centuries to promote better health. Scientific research has shown that polysaccharides (complex sugars) isolated from the fungus prevent fat cell formation in diabetic mice, and other isolates promote antidiabetic activity. Scientists in Taiwan were curious as to whether G. lucidum had any effect on body weight and obesity-related disorders such as chronic low-grade inflammation which leads to insulin resistance, type 2 diabetes, and fatty liver disease, and they published their results in Nature Communications.

The researchers tested whether water extract of G. lucidum mycelium (WEGL) can decrease obesity in high fat diet-fed mice (HFD).  A group of mice was fed a control chow diet, while another group was fed a high fat diet for 8 weeks. The chow and HFD-fed mice were treated daily with either water or WEGL at 2, 4, or 8% for two months.

The obese-human microbiome is often characterized by an increased Firmicutes- to-Bacteroidetes ratio. The researchers examined the gut microbiome of the mice and found that treatment of HFD-fed mice with 4% and 8% WEGL reduced the bacterial ratio to resemble one similar to that of chow-fed mice. In another test, 8% WEGL HFD-fed mice had an increased variety of bacterial species that negatively correlate with obesity, such as Parabacteroides goldsteinii, Anaerotruncus colihominis, Roseburia hominis, and more.  

WEGL fecal transplants were performed on some mice as well, which determined that it was indeed the altered gut microbiota of WEGL HFD-fed mice that is improved as the obese mice receiving the fecal transplant had reduced weight and a reduced Firmicutes-to-Bacteroidetes ratio. Overall, it appears that WEGL affects the gut microbiome of HFD-fed mice in a way that alters it to more closely resemble the microbiome of chow-fed mice. It was discovered that the high molecular weight polysaccharide fraction of WEGL may be responsible for its beneficial effects. While this is an exciting finding, this study was conducted in mice and it will be important to better understand the impacts this has on humans before people are out buying these mushrooms with the hope that it will lead to decreased obesity. 

Introducing specific molecules in the gut could help protect beneficial bacteria

(this is a caffeine molecule, not what was used in the study but something we could all use on this Friday morning)

Antibiotics save countless lives by fighting off pathogens in the body, however they also kill beneficial bacteria in the body that are necessary for keeping us alive and healthy. A team of scientists in Portugal and Spain may have found a molecule that can help restore beneficial bacteria in the gut.

Quorum sensing is how bacteria interact and coordinate with one another. The scientists showed that by increasing levels of a specific quorom-sensing molecule, autoinducer-2 (AI-2), in the gut, mice that had been given antibiotics were repopulated of beneficial bacteria.

The scientists sequenced the bacteria in fecal samples of mice before and after a 28-day regimen of streptomycin treatment. Prior to antibiotic treatment, bacteria of the Bacteroidetes and Firmicutes phyla made up 48 and 43 percent, respectively, of the bacteria in the gut. After 28 days, diversity in the guy decreased significantly and the Bacteroidetes and Firmicutes ratios shifted to 90% of Bacteroidetes species and Firmicutes species made up only 0.7% of all species.

They then repeated this experiment but also generated E. coli that were mutated and not able to absorb AI-2 and introduced these bacteria into the mice that were treated with antibiotics. They used E. coli because streptomycin increases levels of E. coli in the gut when exposed to it. This resulted in AI-2 levels in the gut to be increased as well as increase of bacteria from the Firmicutes phylum, which had been greatly destroyed by the antibiotic in the previous experiment.  

They were able to increase AI-2 levels and therefore beneficial bacteria by introducing bacteria that could not absorb it.  AI-2 could also be directly given to individuals who were given antibiotics and the scientists are now working on developing drugs that would release AI-2 only in the gut. However, antibiotics are not the only cause of dysbiosis.  Diet and other factors can result in changes to gut bacteria and by introducing this molecule and other molecules that bacteria use to communicate with one another, it may be possible to treat gastrointestinal diseases as well as dysbiosis caused by external factors. 

Does eating fermented foods help you lose weight?

Kimchi is a Korean food that traditionally consists of fermented cabbage and spices.  It is a staple in the South Korean diet, and is one of the most frequently consumed fermented foods.  The presence of bacteria in the kimchi has led many to speculate that it can exert a positive influence on the microbiome, and kimchi is believed to have anti-obesity effects.  In order to test this hypothesis researchers from South Korea conducted a clinical trial in which they put obese women on a kimchi diet.  The women were split into two groups, one of which consumed fermented kimchi, while the other consumed non-fermented kimchi.  A summary of the study was recently published by Molecular Nutrition and Food Research.

Surprisingly, fermentated kimchi did not appear to affect the women’s body measurements or specific health indicators when compared to the non-fermented version.  For example, women on both diets had similar decreases in weight, waist circumference, body fat, blood pressure, and cholesterol. There were some important differences though, fermented kimchi increased fasting insulin levels and fasting blood glucose.

The scientists also measured the two groups’ gut microbiomes and blood gene-expression in the study.  The group that ate fermented kimchi had higher abundances of Bacteroides and Prevotella in their microbiomes, and an increased Bacteroides/Firmicute ratio, which has been linked to weight loss.  Bifidobacterium longum, a major lactic acid bacterium that ferments kimchi, has also been linked to weight loss, and to this end, a significant correlation between an increase of this bacterium in the microbiome and decrease in waist circumference was observed.    In addition, a gene known as Acyl-CoA synthetase long-chain family member 1 was found to be significantly upregulated in subjects consuming fermented kimchi compared to those consuming fresh kimchi. This gene plays an important role in metabolism, and it is important in breaking down fatty acids. A second gene, aminopeptidase N (ANPEP) was also expressed more in subjects consuming fermented kimchi.  ANPEP is important for regulating inflammation, and has been associated with a healthy blood pressure.

Overall, this study showed fermented kimchi possibly has beneficial effects on metabolism and immunity when compared to the non-fermented variety. While this study is limited by its small sample size, among other factors, it still shows that the bacteria involved in the fermentation process could benefit us in more ways than we currently know.  These bacteria not only make kimchi taste good, but they may make us healthy too!

Microbiome link between cystic fibrosis and liver disease

Scientists have discovered a possible link between the microbiome and liver disease in individuals with cystic fibrosis.  Cystic fibrosis (CF) is a genetic disease that can be fatal and affects 30,000 people in the United States with another 1,000 diagnosed every year. While pulmonary disease is the most common cause of death in patients with CF, liver disease results in 2.5% of deaths and occurs in up to 72% of patients with the disease.  Approximately 5-7% of  these liver diseased CF patients have cirrhosis, a disease marked by the replacement of healthy liver tissue with scar tissue, preventing the liver from properly functioning.

A team of scientists from University of Colorado Medical Center recently published a study pertaining to CF patients with liver disease  in PLoS One. They studied 11 adolescents with CF and cirrhosis as well as 19 age-matched adolescents with CF without liver disease. They found that the two groups of patients had different gut microbiomes, leading the researchers to believe that there is communication between the gut bacteria and the liver, specifically in CF patients.

Patients with CF and cirrhosis had more severe lesions in their intestines than those without liver disease. Also, specific bacteria were less abundant in cirrhosis patients (e.g. Bacteroidetes) and others more abundant (e.g. Firmicutes) compared to CF patients without liver disease.    Similar ratios have been seen in other studies of liver disease and obesity.  However, we must remember that in complex diseases like CF, the microbiome is only one component of a very dynamic ailment, and at least one other disease study has measured the opposite Bacteroidetes/Firmicutes abundances.

Despite differences in previous studies and the lack of a mechanism relating the microbiome to cirrhosis, this identification of bacterial differences between CF patients with and without liver diseases is promising. The authors of the study point out that the sample size was small and this was only meant to be a pilot study but further longitudinal studies may now be warranted to investigate the development of cirrhosis in cystic fibrosis patients.