Study shows different microbiomes associated with ingesting artificial sweetners

Last year a very important study showed how eating artificial sweeteners could actually increase risk of obesity and diabetes due to a microbiome-mediated response.  Based on this study, researchers from George Mason University investigated the microbiome differences between folks that eat artificial sweeteners, like aspartame and acesulfame-K, and those that do not.  They published their results in the journal Annals of Epidemiology.

The researchers surveyed 31 adults and gave them a questionnaire regarding their eating habits over the previous four days.  Then, on the 5th day the scientists measured the bacteria and the genes those bacteria expressed in each subjects stool.  The scientists learned that the microbiomes did not vary substantially between the two groups, but there were statistically significant differences in the overall diversities of the groups.  In addition, there were no significant differences in the genomes of the bacteria, again suggesting the microbiome is not considerably affected by the ingestion of these sweeteners.  Unfortunately, the authors did not comment on which differences they perceived as being important.

This article suffered from many flaws in its analysis, so we take the results with a grain of salt.  Nonetheless, epidemiological studies in humans like this one are important in supporting the conclusions of studies that demonstrate effects in mice.  The cost/benefits of eating artificial sweeteners versus regular sucrose are still being evaluated, so in the mean time we encourage our readers to eat lots of veggies.

Antibiotic exposure during pregnancy may increase risk of obesity in children

We’ve talked a lot about the importance of a woman's microbiome during pregnancy.  Microbiota transfer from the mother to the fetus is critical toward development, having potential downstream health implications for the child.  Researchers in Denmark have recently pointed to the significance of the maternal microbiome with respective to risk of developing obesity during childhood.  Specifically, prenatal infection and neonatal antibiotic use are both associated with childhood obesity.  Researchers wanted to explore further and determine whether or not antibiotic administration prenatally is associated with childhood obesity.  

9,886 Danish children between the ages of 7 and 16 years old were analyzed over 10 years, and information was collected from routine school anthropometric evaluations.  To determine which of the children were exposed to antibiotics prenatally, prescription dispensations and infection-related hospital admissions information was collected from the mothers’ of the children.  Of all the children assessed, 3,280 – or 33% - were exposed to antibiotics prenatally. 

Among all 9,886 children, 768 (7.8%) were overweight as determined by body-mass index ratios.  Increase overweight incidence was correlated to antibiotic use during the second and third trimester.  309 (3.1%) children were considered obese.  Children with obesity were associated with increases in the number of antibiotic prescriptions for the mother.  Overall, antibiotic exposure prenatally was associated with a 26-29% increase in prevalence of both overweight and obesity in childhood. 

These findings point to an interesting relationship that deserves further exploration.  As mentioned, antibiotics have been shown to disrupt microbiome transfer from mother to fetus.  In addition, microbe-associated molecular patterns in development have been shown to be disrupted by antimicrobials.  These agents could also possibly disrupt endocrine and metabolic systems, leading to impaired energy homeostasis and metabolism, and consequently downstream weight issues. 

Obesity is becoming a major health concern for the global population.  Elucidating more information on the molecular underpinnings of the association between antibiotic use and prenatal development could help reveal more information, and perhaps create awareness of maternal antibiotic intake during pregnancy and/or encourage therapeutic intervention in children with obesity. 

Too much vitamin B12 may cause acne

I first paid attention to vitamin B12 when my friend was touting it as a hangover cure. As it turns out, vitamin B12 is a bit more important than just stopping a headache after drinking alcohol. This vitamin is important for proper functioning of the brain, the formation of blood, among many other functions.  A recent study also found that when we have too much vitamin B12, it may be affecting our skin microbiome in a negative way causing acne. Many people have said that taking B12 has given them acne; however, there had been little research into why this happened. Scientists at UCLA investigated this and published their results in Science Translational Medicine. 

The team of investigators studied the skin bacteria of individuals with severe acne and those without and looked at the gene expression patterns. They found that people taking B12 supplements ended up with higher levels of the vitamin in their skin. They found that this resulted in Propionibacterium acnes, the bacteria implicated in acne, to lower its own production of B12, which is important for performing normal functions. This imbalance resulted in the production of porphyrins, a molecule that is implicated in inflammation and possibly resulting in acne formation.

As with all things microbiome and the human body, it’s important to have a positive equilibrium. Just last night I was speaking with a friend who is undergoing significant microbiome troubles since travelling to Africa in March. When she returned she had major stomach problems and was told to take a course of ciprofloxacin that only worsened her symptoms. She now finds herself with severe vitamin B12 deficiency and anecdotally she mentions slight memory loss, a common symptom of B12 deficiency. Like everything in our body, it’s important to find that middle ground and those with acne shouldn’t yet be starving themselves of vitamin B12. This study did not prove that too much B12 causes acne and in fact other studies have shown that the vitamin has anti-inflammatory effects. More work will be needed to show if this is in fact causal and if new treatments for acne can be designed using this new information about vitamin B12. 

Bacterial vaginosis associated bacteria may increase a women’s risk for miscarriage

Bacterial infections or even slight imbalances can be damaging at many difference locations in the human body. One that should be taken seriously in bacterial vaginosis, which is an infection in females where a healthy bacterial balance is taken over by bacteria such as Gardnerella vaginalis, Ureaplasma urealyticum, and Mycoplasma hominis to name a few. Meanwhile, the presence of Lactobacillus crispatus and Lactobacilus iners would be characteristic of a normal vaginal microbiome. In a study out of Philidelphia, Pa that was recently published by Maternal and Child Health Journal, researchers inspected a possible connection between bacterial vaginosis and pregnancy miscarriages.

          A total of 418 pregnant women were included in the study. 65% of the women were African American, 27% were Hispanic, and 4% were Caucasian. Women were eligible if they were seeking treatment prior to 14 days of gestation, if they were not pregnant with multiples, and if there were no issues in terms of ectopic or molar pregnancy. Swabs were collected from the women and analyzed. During this study, 74 women experienced a miscarriage, while 344 delivered at term.

          It was found that the group of women who had miscarriages were older than those who did not. Women with high concentrations of Bacterial Vaginosis-Associated Bacterium 3 (BVAB3) before 2 weeks gestation had a 20% increased chance of miscarriage. On the other hand, for each one unit increase in Leptotrichia/Sneathia species concentration, risk of miscarriage decreased by 20%, and for that of Megasphaera phylotype 1-like species risk decreased by 19%. The implications of this type of research could be very beneficial to women everywhere. More knowledge like this could hopefully one day lead doctors towards even better care for pregnant women. Ideally, with more research into this area, the prevalence of miscarriages could be lowered. 

Pathogenic microbiome bacteria change shape to adapt to nasopharyngeal environment

Microbiome bacteria are highly adapted to their surroundings.  They face constant pressure from the immune system as well as other bacteria, fungi, and even small molecules such as antibiotics.  It should come as no surprise then, that many of these bacteria have undergone major evolutionary adaptations to survive the human body.  Apparently, as discovered by French group and published in PLoS Genetics, one common strategy amongst many different bacteria is a shift from rod shaped to spherical shaped (coccoid). 

The scientists investigated the genealogy of bacteria for the family Neisseriaceae, which have species with a high diversity of shapes, including some members from the human nasal microbiome, like Neisseria meningitidis that are spherical.  In tracing the histories of this bug they noted that many other bacterial species showed a similar tendency, that is they converted from rod to coccoid after entering the nose.  The researchers were even able to track down the simple genetic mutations responsible, and they noted that this mutation to coccoid conferred many fitness advantages over the rod shape.  For example, the coccus shape has a higher surface to volume ratio than the rod, so that the host immune system has less surface to detect, without sacrificing as much volume in the cell.

It is interesting to look into the evolutionary developments of microbiome bacteria, because they shed light on the shared strategies of these commensals in coexisting with their host.  These adaptations actually differentiate the commensals from the non-commensals which are potentially pathogenic, because foreign bacteria don’t stand a chance of evading our immune system, especially compared to bacteria that have evolved with us throughout the entirety of human history. 

A new way in which some gut bacteria rely on their hosts’ mucous for energy

It is often understood that our gut bacteria live off of the foods we eat.  However, many gut bacteria can actually metabolize the mucous that protects the lining of our gut.  In fact, many bugs have the ability to digest a specific sugar that is attached to our mucins, called sialic acid.  Interestingly, some bacteria have the ability to cleave this sugar from the mucins, others have the ability to consume this sugar once it is released, and others have the ability to perform both of these tasks.  Last week, a new method for how gut bacteria can transform sialic acid was discovered, that some bacteria can actually transform sialic acid before cleaving it, and that this may be clinically relevant for Crohn’s disease and colitis.  The authors published their results in Nature Communications.

The authors were testing a common commensal bacteria, Ruminococcus gnavus, and noted that it had the ability to both cleave and consume sialic acid from gut mucins.  When they identified the metabolites from this process they discovered that the sialic acid was actually being converted to a different form by these bugs.  After further experimentation they realized that a type of enzyme, called an intramolecular trans sialidase, which had never before been observed in gut bacteria, was responsible.  The researchers then compared the genes from R. gnavus to other bugs common in the gut and noted that a full 11% of human gut commensals had this enzyme, and that these bacteria were overrepresented in people with IBD.  The authors think that the bugs who code for this enzyme have an inherent advantage over other gut microbiota because after they transform the sialic acid they can still use it for energy, whereas other bugs cannot, leaving the sugar all to themselves. 

The paper did not discuss specific mechanisms as to why these bugs may be overrepresented in Crohn’s and colitis.  They did however test a few molecules that inhibited the activity of the enzymes.  Perhaps if these enzymes or the responsible bugs are the cause of IBD, than these inhibitors could be used as therapeutics to combat the disease.