Emidermolysis bullosa, a severe skin disorder, may be influenced by skin microbiome

Epidermolysis bullosa (EB) is a terrible hereditary disease that results in blistering skin and can become so severe that the skin falls off the body (I highly recommend that you do not search for images of the disease, really). Severity levels vary but this disease can be lethal and the age of death is often very young. While recently many stem cell research advancements have been made bringing new treatments to young patients, treatments for the disease are lacking and a full understanding of the disease is not complete.

EB is a disease that is characterized by antibodies that target type VII collagen (COL7), an important part of the skin. In previous experiments, when mice are immunized for COL7, skin blisters result in 80% of the mice however 20% of mice remain healthy. To look at why this happened, scientists in Germany looked at the innate and adaptive immune response of mice that were healthy and compared this to the mice that became sick after immunization and published the results in the Journal of Autoimmunity.

They studied the skin microbiome of the mice by taking a biopsy prior to immunization because the skin microbiome has been shown to influence cutaneous inflammation. One of the major findings was that in the mice that did not develop the clinical symptoms of EB, there was greater richness and diversity of the skin microbiome before immunization. This showed that the results of the experiment could have been predicted prior to experimentation and therefore is an important factor in future studies looking at the transition from autoimmunity to the onset of autoimmune disease.

These results also lead us to the conclusion that it may be possible to prevent or reduce clinical inflammation in autoimmune disease by influencing the skin microbiome. 

Hormonal contraceptives are associated with altered cervical immunity, dependent on the presence of genital tract infections

Past studies have shown an association between hormonal contraceptives and risk of HIV-1 infection, as well as between genital tract infection and acquisition of HIV-1. The types of hormonal contraceptives that have been associated with increased risk of HIV include progestin injectable depot medroxyprogesterone acetate (DMPA) and combined estrogen-progestin oral contraceptives (COC). Untreated cervical pathogens such as Trichomonas vaginalis, Neisseria gonorrhoeae, Chlyamydia trachomatis, Candida albicans, and genital herpesvirus 2 also contribute to increased risk of HIV. In a study recently published in mBio by the American Society for Microbiology, researchers investigated the combined effects of hormonal contraceptives and genital tract infections on risk level of HIV.

The participants of this study were 633 HIV-negative women and 199 HIV-positive women, all of whom live in Uganda or Zimbabwe. It was found that more than half the study participants were positive for herpes. Cases of herpes were evenly distributed among women with chlamydia, candidiasis, and bacterial vaginosis. However, herpes was significantly more common among women positive for T. vaginalis or gonorrhea. As for contraceptives, women with asymptomatic infections were mainly COC users (65%) followed by DMPA users (60%). Symptomatic infections were most common in the group that did not use hormonal contraceptives.  

To test for risk factors of HIV, the researchers looked at certain immune system response components. It was found that HIV was associated with higher levels of two immune components known as RANTES and BD2. RANTES was seen to be increased among combined estrogen-progestin oral contraceptive users whom were also associated with herpes and abnormal vaginal microbiota. BD2 was seen increased among COC and non-HC users by T. vaginalis infection and among DMPA users by herpes, candidiasis, and bacterial vaginosis.

As is common in all processes of life, there seem to be many factors that contribute to HIV infection. Changes in the immune system caused by hormones, like contraceptive hormones, and genital bacteria composition may combine to influence vulnerability to HIV infection. This study is important, because the more knowledge scientists have about women’s reproductive health, the greater the possibility that we can develop treatment and prevention plans for infections.

New study suggests gut microbiome directly influences BMI, triglyceride, and HDL levels

Molecular structure of cholesterol

The microbiome has long been associated with cardiovascular disease, especially after studies showing differences between the gut microbiomes of obese and slim individuals.  The mechanisms by which the microbiome may be influencing heart disease are still unknown, but there are a few mechanisms that have been identified.  For example, as has been previously discussed on this blog, trimethylamine N-oxide (TMAO) in the blood is an independent risk factor for atherosclerosis, and is produced by gut bacteria from choline and carnitine.  In addition, systemic, chronic inflammation is associated with heart disease, and our avid readers will know that the microbiome can cause chronic inflammation in the vagina, gut, and mouth.  Overall though, a direct relationship between specific bacteria and heart disease has not been shown.  A recent epidemiological study though, did just that.  The researchers, mostly from the Netherlands, were able to identify specific species that were associated with higher BMIs, as well as those that were directly correlated with HDL cholesterol levels.  They published their results in the journal Circulation Research.

The scientists measured the genomes, microbiomes, BMI, and blood lipids of 1500 adults.  Their results showed that higher overall diversity and richness of the gut microbiome was associated with a lower a lower BMI (healthier state), lower triglycerides (healthier state), and higher level of HDL cholesterol (healthier state).  The diversity was not, however, associated with total cholesterol nor LDL levels.  The researchers then identified specific bacteria associated with these health indicators.  There are too many to list in this blog, so we encourage interested readers to take a look at the article.  Some examples though: Akkermansia, Christensenellaceae, and Tenericutes were each associated with low BMI, low triglycerides, and high HDL (all healthy states), while Eggerthella was associated with high BMI and high triglycerides, and Butyricimonas was associated with high BMI, high triglycerides, and low HDL (all unhealthy states).  Finally, the researchers sought to determine just how important the microbiome was to overall BMI, triglyceride levels, and HDL levels by incorporating the host genetics, age, and gender into their calculations.  They showed the 4.5% of the variance in BMI, 6% of the variance in triglycerides, and 4% of the variance in HDL is directly attributable to the microbiome.

These study results reaffirm the importance of the microbiome to our overall health, and even quantitatively show its influence on specific health indicators.  The authors do not attempt to explain why specific bacteria would cause variation in these metrics, although as previously mentioned some mechanisms have already been demonstrated.  To check to see which other diseases these bacteria have been associated with, use the search tool, or click the tags below to see all the blog articles that mention them.

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.

Ingesting blueberries and oats may modulate the microbiome and help diabetics

Prebiotics are foods that are consumed in order to modulate the microbiome.  They are normally composed of molecules that are not broken down by our body itself, but rather that remain intact until making it to the large intestine where bacteria can break them down.  Common prebiotics come from plant materials, like long chained complex carbohydrates, as well as polyphenols, like blueberry extract.  In a recent study, scientists from Louisiana State University performed randomized dietary intervention on obese subjects and gave them a mixture of these molecules.  They then monitored the changes in the microbiome that occurred, along with changes in health indicators.  Their results were published in The Journal of Diabetes and its Complications.

The researchers included 30 adults in the study, and split them into two groups: one to receive the microbiome modulating dietary supplement, and the other to receive a placebo.  The dietary supplement included blueberry extract, oat bran cellulose, and inulin (a common oligosaccharide of fructose).  The subjects ingested the supplement daily for four weeks, with samples being collected once before and once at the end of the sudy.

Many positive health consequences were associated with eating the prebiotics.  Those patients had improved glucose tolerance, as well as increases in satiety.  The satiety may have been caused by an increase in fasting PYY concentration, a peptide known to cause hunger suppression, which was higher in those people taking the prebiotic.  In addition, there was an increase in self-reported flatulence from taking the prebiotic, but otherwise no adverse events were recorded.  Interestingly, there were no statistically significant changes in the microbiome that resulted from eating the supplement, however higher levels of short chained fatty acids (SCFAs) were observed in the stools of those patients.  Even though no statistically significant change was measured, it is quite possible that the level of sequencing depth and analysis was robust enough to truly observe changes that may have occurred.

This study is another that shows the benefits of eating prebiotics.  Interestingly, the prebiotic used for this study is the same one used by Microbiome Therapeutics in their metformin formulation.  This prebiotic, when combined with metformin, increases its efficacy for diabetics.  This study shows that possibly the prebiotic alone is responsible for this improvement, although it gets us no closer to explaining how this occurs.  Any of our readers that are taking metformin may want to read the wealth of literature around what Microbiome Therapeutics has done, because just the simple addition of foods to the drug seems to improve the results of taking it.

Antibiotic exposure may increase risk of cancer

The microbiome has been implicated in several cancers including gastrointestinal and breast cancer with many hypotheses proposed as to why bacterial dysbiosis is associated with cancer onset. Recent studies in mice as well as epidemiological studies have provided further evidence that specific bacterial composition led to tumor formation and this could be blocked by antibiotics. In a new study, scientists at the University of Pennsylvania aimed to use epidemiological data to evaluate the association between antibiotics and cancer risk of the skin, lung, breast, gastrointestinal and genitourinary tract. 

The scientists used data from The Health Improvement Network (THIN) database, a medical record database from the United Kingdom containing the information of approximately 11 million individuals. They looked at 15 different malignancies and in order to focus on sporadic cancers, they excluded any individuals with family cancer syndromes as well as any subjects that were diagnosed prior to the age of 20. With every case of cancer, they used four matched controls resulting in 125, 441 cases and 490, 510 controls analyzed for the study.

They found that the use of penicillin resulted in an increased risk of esophageal, gastric, and pancreatic cancers and was 1.4 for gastric cancers associated with greater than 5 courses of antibiotics. Lung cancer risk also increased with penicillin, cephalosporins, or macrolides. Prostate cancer also so a slight increase with several types of antibiotics as well as breast cancer after sulphonamide exposure.

They found for any type of malignancy there was no association between a single course of antibiotic use and increased risk but there was a correlation between greater number of antibiotic courses and cancer risk. Penicillin was associated with the most significant cancer risk while anti-virals, anti-fungals, and tetracylines were not associated with increased risk of cancer. While the increase in incidence was quite small (approximately 20:100,000), it is an important finding that antibiotics may be having a wider impact than previously believe. It is important that future studies look at the mechanisms for how antibiotics are causing this increased cancer risk as well as the effects of age of antibiotic exposure on cancer risk.