Antibiotic use in children may increase risk of obesity

We’ve talked extensively on the blog about antibiotics and the both positive and negative effects they can have on people’s health. Marty Blaser, professor at NYU School of Medicine and the world leader in studying antibiotics and their role on obesity and other health effects, published a study in Nature Communications last week on the effects that antibiotics can have if administered early in life.

Dr. Blaser and his colleagues used mice to administer various antibiotic regimes that included amoxicillin and macrolides. They provided the mice three antibiotic treatments, called pulsed antibiotic treatment (PAT), to the mice to mimic frequent antibiotic use in children. They found that the mice that were given the PAT saw short-term increases in weight as well as bone growth, specifically increased bone growth after amoxicillin treatment and increased fat after tylosin (macrolide) treatment.

The scientists also saw long-term alterations in the gut microbiota of mice given a PAT regime. Mice that were given antibiotics had decreased microbial diversity different proportions of bacteria compared to control mice. Surprisingly, the change in microbiome persisted until the time of the mouses' deaths, 120 days after the last antibiotic treatment. They also saw differing gene expression in the mice that were given pulsed antibiotic treatments. These two results give evidence that antibiotic use is leading to permanent physiological changes in the body. 

Dr. Blaser has long been telling us that the early stages of life, the time when we most frequently administer antibioitics, is critical to development and that antibiotic use can drastically alter this development. This study supports other research by Dr. Blaser and colleagues that has shown that antibiotic use in early life predisposes us to obesity.

While we know antibiotic use can have these negative long-term effects, they are still essential and are life-saving drugs for when we have bacterial infections. The authors state that this work and other work showing the negative effects antibiotics can have should lead to increased awareness as well as a re-examination of policies and guidelines to antibiotic use in humans. 

What bacteria live in the gym?

A lot of research goes into understanding the complexity and dynamics of the human microbiome in the GI tract or the mouth, to name a few locations. In an article published by Microbiome, researchers at Northwestern University took a different perspective in that they looked at how the human microbiome affects the environments around us. A very interesting point raised by the article is that Americans spend most of their time in so-called “built environments,” which are indoors. The microbes of these indoor environments are mainly affected by the humans that interact with them, so the scientists at Northwestern University took to studying how the bacterial composition of indoor athletic equipment and facilities are affected. This specific environment was chosen mainly because of the numerous different human encounters it experiences.

For 2 days, the researchers collected swab samples in 3 athletic facilities. Samples were collected every 2 hours from the floor, mats, elliptical handles, free weights, and benches from 8 am to 6 pm, and a total of 356 samples were collected.  After sequencing and analysis, the researchers concluded that, consistent with all three facilities, the bacteria found on the equipment was most likely to be from the human skin, with Pseudomonas and Acinetobacter showing up in the most samples. Besides microbiota from the skin, other bacteria were found to be abundant such as Bacteroides from the human intestinal tract on elliptical handles and Finegoldia, also from the GI tract, on benches.

As for which sampled location had the most stable bacterial community, it was found that the floor and mats showed the least change in structure. This is most likely because elliptical handles, free weights, and benches come in more direct contact with human skin. Across the board, the only genera which were found in all samples from every surface type were Staphylococcus and Pseudomonas. It is important to remember that none of this means athletic facilities are blooming with harmful bacteria, and we should stay far away. In fact, the environment is not very conducive to the thriving of bacteria, because it lacks a lot of resources. What we should take away from this study is that any surface that comes in contact with human skin is likely to reflect the microbiome of that person. 

Probiotic shows effectiveness against skin allergy in mice

We’ve talked about atopic dermatitis on the blog before, because more and more evidence is linking this autoimmune disease with the microbiome.  In fact, a few weeks ago we wrote about a strong connection between Staphylococcus aureus and atopic dermatitis, which suggests this bug is the culprit behind the disease.  If atopic dermatitis does have a microbiome cause, then it makes sense that shifting the microbiome could help alleviate the disease.  This past week researchers investigated whether probiotics, specifically Lactobacillus casei, could help treat this disease in mice.  They published their results in the Journal of Applied Microbiology.

Scientists induced groups of mice to have atopic dermatitis by shaving their skin and challenging them with a molecule called trimellitic anhydride (TMA) on various days over the course of two weeks.  During that time, the scientists orally administered the probiotic to some of the groups of mice.  Over the course of the study the scientists measured various things like the changes in the microbiome and the amount of various immune-activated molecules, as well as dermatitis indicators, such as skin lesions and the amount of itching.  They discovered that the mice that took the probiotic had less severe symptoms than those that did not.  What’s more, is that this reduction of symptoms occurred in a probiotic dose-dependent manner, i.e. the more probiotic administered, the better the symptoms.  These symptoms included a reduction in the inflammatory response, as well as a desensitization of the TMA, as evidenced by less itching.  As for the microbiome, treatment with TMA decreased abundance of Bifidobacterium and Lactobacilli, and an increased abundance of Clostridia.  Probiotics on the other hand, increased the abundance of Lactobacilli and Bacteroides and decreased the abundance of Clostridia. 

This study is not the first to show in a health improvement through the administration of Lactobacillus, which we have written about before.  It seems this bug is almost always associated with health, except in the case of respiratory diseases.  Overall, it seems that you can’t get enough Lactobacilli, so the next time you are considering having a second serving of yogurt for breakfast, go right ahead.

What happens to dietary fiber after we eat it?

Complex carbohydrates from dietary fiber, such as from fruits and vegetables, are, with some exceptions, largely indigestible to normal human metabolism.  These polysaccharides though, form the basis for much of the gut microbiome’s nutrition because they pass into the colon largely unaffected.  For this reason, many scientists are considering complex carbs as prebiotics, or foods that can manipulate the microbiome to improve health.  At this point in time, the fate of many prebiotics in the gut, and the mechanisms by which they are broken down and shared by the microbiome bacteria, are still largely unknown.  Last week a paper in Nature Communications investigated this question, and measured the breakdown of complex xylose molecules in the gut.

The researchers discovered that Bacteroidetes have many different enzymes to break down complex xylans, and regulate and induce different ones based on the type of xylan, e.g. whether or not it has many long chains stemming from its backbone.  They then discovered that these enzymes work in conjunction with one another to break down highly complex structures into smaller oligosaccharides.  These breakdown products are often released into the lumen of the gut where other bacteria can feed on them.  As it turns out, the initial xylan is most important to determining which smaller xylans are produced by Bacteroidetes, and therefore which other bacteria will benefit from the xylan metabolites.  Taken together, this study illustrates the complex ecology of the gut, with some bacteria breaking down large carbohydrates into smaller pieces, and other breaking those down into even smaller pieces, until finally a xylose monosaccharide is broken down into a short chained fatty acid.

Overall, this study lends itself to the value of prebiotics.  Clearly, the food we eat affects the composition of the microbiome.  We are now learning the mechanisms by which this happens, through a hierarchical food chain in the gut.  Once these are completely understood scientists should be able to produce foods that will controllably alter the populations of the gut, which could lead to methods to combat a variety of diseases.

Asthma could be brought on by maternal diet and lack of bacterial metabolites

Asthma has become increasingly prevalent in Western societies, and while many theories have been explored as to the reason for this rise in prevalence, many are beginning to explore connections between dietary intake and associations with the microbiome as a manifestation for this malady.  High fat, low fiber diets – which are common in the West – are associated with high rates of asthma.  Investigators in Australia sought to explore this relationship further by understanding the cellular underpinnings of these associations.  Specifically, they explored whether or not high fiber diets in mice could suppress the onset of Allergenic airway disease (ADD -i.e. asthma).  Furthermore, maternal fiber intake was also examined to see what affects would result for the progeny when challenged with asthma inducing conditions.  They published the results in Nature Communications.

Using 16S sequencing the researchers first confirmed that the high fiber diet shaped gut microbiome composition in mice.  Specifically, a significant difference was observed between control diet and no fiber diet.  Bacteroidetes were highly abundant in mice that were fed the high fiber diet, including high acetate producing Bacteroides acidifaciens strain, while Proteobacteria were found abundant in the no fiber diet.  High fiber diet mice also displayed higher levels of short-chain fatty acids, metabolic products of the gut microbiota that provide overall positive health benefits. 

Turning next to the pathology, experimenters were first able to validate that HDM did indeed induce AAD, as confirmed by inflammatory cells and signal markers found in the bronchoalveolar fluid of mice.  Indeed, mice that were on the high fiber diet did not develop AAD symptoms.  Interestingly, this was also shown in control animals who were administered HDM but were provided acetate (a short-chain fatty acid) in their drinking water. 

Mice were then bred and split into three dietary groups based on diet, a control group, high fiber group, and no fiber group.  Allergenic airway disease (AAD) was induced using a house-dust mite (HDM) model which replicates certain aspects of human asthma.  Diets were provided three weeks prior to sensitizing the animals to HDM, and AAD was evaluated after 16 days following 15-day HDM exposure.

Pregnant mice were also subjected to the three different diet regiments in the previous experiment.  The offspring were born and given a control diet, but after 6 weeks they were administered AAD.  The mice that were born from mothers on the high fiber diet did not develop AAD into adulthood, demonstrating that maternal diet can suppress AAD in adult offspring.  Interestingly, these findings were correlated with human data that demonstrated that high fiber diets in mothers’ in late-stage pregnancy was correlated to high acetate in serum samples.  Maternal acetate levels above median levels of samples taken was associated with significantly less visits to the general practitioner for wheezing complaints and/or asthmatic incidences in their children.    

Increasing numbers of studies are showing similar patterns that behaviors of the mother can affect microbiome transfer to progeny, consequently affecting the health and development of the offspring.  One of these important factors as we have seen is the diet of the mother.  As further evidence is uncovered as to the importance of high fat diets and specifically the diet of the mother, it will be important to have conversations on the best way to educate the public about this evidence as well as implement recommendations for dietary habits during pregnancy. 

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.