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.

Bacteria from infants’ microbiome metabolize breast milk differently.

Human milk oligosaccharides (HMOs) are a diverse group of carbohydrates found in breastmilk.  Because the HMOs can’t be used by the infant directly for energy, scientists believe their purpose is to stimulate the development of a healthy gut microbiome.  During the first year of life, an infant’s gut is dominated by Bifidobacteria, in particular B. infantis, and B. bifidum.  In a recent publication scientists measured the difference in HMO utilization between these bugs, and discovered they have very different and important strategies for HMO utilization. The results were published in Nature Scientific Reports.

The scientists first isolated multiple strains of each species, B. infantis and B. bifidum, from the feces of newborn infants.  They then attempted to culture each strain alone in a mixture of HMOs from breastmilk, as well as the individual HMOs alone.  They learned that the each B. infantum strain could grow on pooled HMOs, but interestingly some of the B. bifidum strains could not grow alone on HMOs.  When the bacteria were cultured with mucins (containing sialic acid or fucose, as previously discussed on this blog) none of the B. infantis could grow, whereas most of the B. bifidum could.  This implies that B. infantis alone cannot utilize fucose or sialic acid, but rather needs the help of other bugs to break these down to utilize them.  After, the scientists looked at the regulation of different genes during the culturing experiments.  From these results they determined that B. infantum transports the HMOs inside the cell before breaking them down for energy.  B. bifidum, on the other hand, breaks the oligosaccharides down extracellularly before taking up smaller, simpler sugars. 

All together we see that there is a complex assemblage of bugs in the guts of infants that all rely on one another for energy and metabolism.  The breastmilk cocktail of HMOs itself is so complicated that it almost necessitates the interdependent communities to grow.  Overall, this creates a robust and resilient microbiome that prevents pathogens from taking hold and protects the infant during his or her most vulnerable years.

New research shows that Bifidobacteria transfer from mother to child

Both natural birth (as opposed to birth by C-section) and breastfeeding are topics that stir up a lot of conversation among mothers and the scientific community. For example, there is the question of whether breastfeeding rather than formula feeding has some specific benefit to an infant’s health. Well, what about the infant’s gut microbial health? A new article published by Applied and Environmental Microbiology takes a look at whether natural birth and breastfeeding coincides with an exchange of bacteria from mother to child.

Four mother and infant pairs were included in the study that was meant to discover whether the mother transfers any bacterial strains to the infant during vaginal birth and breastfeeding. In particular, the scientists were looking at the genus Bifidobacterium because this group has been known to be early colonizers of the infant gut. In addition, this genus has specific ways of digesting a human mother’s milk. Mother-infant pairs 2 and 4 exclusively breastfed, while pairs 1 and 3 supplemented with formula. Milk samples were collected from the mothers and fecal samples were collected from the mothers and children.

After sequencing the bacteria, B. adolescentis, B. angulatum, B. breve, B. dentitum, B. pseudolongum and B. thermacidophilum were found to be common between all of the mother and the infant fecal samples. The scientists then looked to see which bacteria were in both the mother’s milk and the infant’s fecal sample. The results suggest that the milk may be responsible for transferring B. adolescentis, B. angulatum, B. breve, B. longum and B. pseudolongum to the infant. Interestingly, there were also some bifidobacteria strains that were unique to the infant, suggesting that either they went undetected in the mother or that the infant was exposed to this bacteria from somewhere else.

After six months, samples were collected again in order to see how/if the sample compositions change. The scientists found that, especially in the infants, the abundance of bifidobacteria decreases. This is most likely due to changes in diet – less breastfeeding and more formula feeding – and perhaps environmental exposure. All in all, the results of this experiment shows that the infant microbiome might indeed be influenced by a vertical transfer of bacteria from mother to child. With more evidence of this as a possibility, science may begin looking into more complete analyses with larger study sizes.  

Schisandra chinensis fruit modulates microbiome in obese women

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.  

The maturation of the microbiome during the first year of life

Dr. Jeffrey Gordon recently published a review article describing the importance of the proper development of the microbiome in the early stages of life.  One paper that certainly would have made it into the review if it was published in time is a new paper published last week out of Sweden and China that studied the developing microbiome of children over the course of their first year of life.

The team of scientists studied 98 women and their newborn babies. They sequenced the mother’s stool, the newborns stool, and again the child’s stool at 4 and 12 months. Throughout the study, because they used a technique called shotgun sequencing, they identified 4,000 new microbial genomes.

The infants in the study were breastfed for varying amounts of time with some never being breastfed at all. The researchers found that breastfeeding and the timeline of cessation of breastfeeding was critical to driving microbiome development. Many had previously hypothesized that it was the time at which solid foods were introduced was most important for microbiome development, however this study found that it was the time at which breastfeeding was stopped. Children that stopped breastfeeding earlier had microbiomes more similar to adults at 12 months while children who were breastfed for the duration of the study continued to have microbiomes dominated by Bifidobacterium and Lactobacillus.

The scientists also found that the 15 babies born via C-section had different microbiomes than the other 83 babies studied.  The infants born via C-section had microbiomes that more closely resembled skin and mouth microbial communities while the babies born vaginally had microbiomes more closely resembling the bacteria in their mother’s stool.

We still don’t know exactly what a “healthy” microbiome looks like and which microbial profile is best for the child. This study provides a very solid experimental design to study the development of the microbiome and allows for the continued monitoring of these children’s microbial development over the course of their lives. 

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

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.