Antibiotics affect the mouth and gut differently

When we discuss antibiotic resistance, it’s not always clear where the resistance is developing or how exactly the resistance develops. A study out of the UK and Sweden looked at two niches, the gut and the mouth, to understand the difference between how the different parts of the body react to antibiotics.

The scientists discovered that these two parts of the body reacted and recovered very differently after a one-week course of antibiotics. They took fecal and saliva samples prior to the antibiotic regime and then gave the study participants a weeklong course of clindamycin, ciprofloxacin, minocycline, amoxicillin, or a placebo and continued taking fecal and saliva samples for a year.

They found that the oral microbiome recovered much faster than the gut microbiome back to its normal state. It took much longer for the gut microbiome to recover and for participants taking ciprofloxacin, diversity was changed even after 12 months. They also found that while participants largely had genes associated with antibiotic resistance in their gut prior to the trial, the amount of antibiotic resistant genes increased after taking the antibiotic. Antibiotic resistant genes in the mouth remained largely stable before and after treatment.  It was also observed that butyrate production, a health associated short-chain fatty acid, was severely affected by ciprofloxacin and clindamycin.

This raises a number of questions like why does the oral microbiome recover so much faster than the gut microbiome? And why isn’t there a similar increase in antibiotic resistant genes in the mouth like we see in the gut? While this study raises many questions, it provides an opportunity to look at the mouth and better understand what is unique about that environment in comparison to the gut. 

Gut microbiome depletion promotes healthier brown fat and reduces obesity in mice

The white and brown turkey meat from a Thanksgiving dinner

An interesting article from Switzerland was published last week in Nature Medicine.  The scientists reported on a new connection between the gut microbiome and metabolic syndrome (i.e. insulin sensitivity, obesity, etc.)  Whereas most papers observe microbiome disruption and depletion is associated with obesity, this paper describes a different phenomenon: that mice with depleted microbiomes are metabolically healthier than their untouched microbiome counterparts.  As part of the basis for the paper it is important to understand that mammals have two types of fat, brown fat and white fat.  Brown fat is associated with exercise, insulin sensitivity, and health, and white fat is associated with insulin resistance and diabetes.  Brown fat can actually repopulate white fat in a process called browning, and this transition is healthy.  

In the study, the scientists started with either normal mice, germ free mice, or mice that had antibiotics administered to them. They challenged each group of mice with glucose, and noted that antibiotic administration led to improved insulin sensitivity.  When they investigated where the glucose was going, they discovered that it was uptaken by white adipose tissue under the skin.  Then, they compared the normal mice and antibiotic mice, and observed that the antibiotic mice actually had smaller volumes of fat after the glucose uptake.  Interestingly, the fat cells in the germ free and antibiotic mice were smaller and more dense, whereas the normal mice had fewer, larger cells.  The researchers then confirmed that browning of fat was occurring in the germ free and antibiotic mice.  Finally, when the scientists transplanted the microbiome of normal mice into the germ free mice a reversal of many the above described characteristics occurred.  In these mice the fat stopped browning, insulin resistance decreased, and the mice gained weight.

The scientists were able to attribute some of the above phenomena to the release of specific cytokines (molecules that regulate the immune system).  This paper, then, adds to the wealth of research that describes the complex but critical interaction between the gut microbiome, the immune system, and metabolic syndrome.  Although the relationships between these things is yet to be fully understood, this paper may at least change the way you think about the dark and white meat during Thanksgiving dinner this Thursday.

Effects of antibiotics on gut microbiome and glucose metabolism

The gut bacteria in the human gut plays an important role in glucose (sugar) metabolism. Alterations to the gut microbiome have been linked to obesity and Type-2 diabetes, as a result of inability to breakdown sugar. Scientists wanted to see the effect of removing as much bacteria as possible using antibiotics and what the effect was on human health after eating meals and published their results in PLOS ONE.

The study design included twelve healthy male volunteers, with a mean age of 23.4 years and no glucose intolerances. The participants were tested 5 separate days (day 0, 4,8, 42, and 180) during the study. Between days 0 and 4, the participants consumed a 4-day 30 drug antibiotic mix, made of meropenem, vancomycin, and gentamicin. On days 0, 4, and 42 the males participated in a liquid meal test, in which blood samples were taken 30, 15, and 0 minutes before and 15, 30, 45, 60, 75, 90,120, 150, 180, 210, and 240 minutes after ingestion of a specially concocted liquid meal. At 270 minutes, the participants were given a solid food meal. On days 8 and 180, blood pressure and sample was taken. The day before each of the 5 visits, the participants collected a fecal sample.

Antibiotic treatment did not seem to cause any serious or unexpected adverse effects. Between day 0 and day 180, an increase of mean body weight was found at only 1.3 kg and the corresponding change in BMI was 0.3. No changes in average blood pressure was observed, nor were any health complaints or symptoms.

As for the gut microbiome, after the 4 days of antibiotics, total anaerobic bacterial count decreased from 8.5 log10CFU/g to 6.2 log10 CFU/g. Enertococci, coliforms and bifidobacteria decreased significantly as well. On day 8 of the study, the abundance of aerobic bacteria had actually significantly increased passed the concentration number before antibiotics were consumed. By day 180 of the study, however, bacterial counts returned to the same baseline level from before antibiotic consumption. Overall, no significant effect on glucose consumption or metabolism was observed in this study as a result of changed gut bacteria composition. 

The microbiome’s response to the flu and its treatment

In 2013 there was an avian flu (H7N9) outbreak in China that affected 140 people, killing 46 of them.  During the outbreak doctors from one of the major hospitals in China treated 40 of these patients by giving them antivirals and antibiotics, amongst other first line treatments.  In addition, they gave probiotics along with the antibiotics to restore the gut microbiome.  All the while, they measured the patients’ microbiomes to track how they changed throughout the course of treatment.  The results of this study were published last week in the journal Nature Scientific Reports.

Twenty six patients were enrolled in the study, and each of them was given antibiotics within 6 hours of admission to the hospital.  In addition, each one was given Clostridia probiotic capsules along with the antibiotics.  Thirty one healthy control stool samples that represented the demographics of those undergoing flu treatment were also measured as a part of the study.  Before the antibiotics were taken, the patients with the flu already had altered microbiomes that were low in diversity and had lower abundances of Bacteroidetes and higher levels of Proteobacteria.  After antibiotics were given there was a dramatic shift in the microbiomes, that was characterized by a relative increase in the abundance of Escherichia coli.  In addition, the scientists noted that the probiotics were in fact increasing the amounts of Clostridia in the guts of patients who took them, and that the probiotics may have led to better clinical outcomes.  In their hospital only 20% of patients died of the flu, whereas 40% died in the rest of China.

The major takeaway from this study is the changes that the flu has on the microbiome, decreasing diversity and altering the levels of certain phyla.  The fact that the probiotics did appear to take hold and improve clinical outcomes is interesting, but the study was extremely small and limited in its scope to reach any statistically significant conclusions.  Overall though, this study suggests that if you come down with a flu that it may be wise to feed and nourish your microbiome because it is ‘getting sick’ right alongside you.

Does the use of antibiotics for bacterial vaginosis during pregnancy reduce the risk of preterm birth?

Bacterial vaginosis (BV) is an inflammatory disease that is defined as a vaginal microbiome that is not dominated by Lactobacilli.  This abnormal vaginal flora is associated with preterm birth and miscarriage.  A recent study showed that women’s vaginal microbiomes shift frequently during pregnancy, but that the amount of time spent with a flora not dominated by Lactobacillus was associated with the length of the pregnancy, i.e. the less time spent with Lactobacillus the shorter the pregnancy.  Considering these studies, doctors may want to begin screening the vaginal microbiome during pregnancy, and treating BV (which is currently done through antibiotics).  Strategies such as that one have not yet been rigorously studied, so their efficacy is still unknown.  Last week a study out of Japan performed a study that showed little improvement in preterm birth risk by monitoring and treating BV during pregnancy.  The results were published in Nature Scientific Reports.

The researchers measured the microbiomes of 1,735 pregnant women and split them into two groups.  Women in the intervention group that had BV were given antibiotics, whereas women in the control group, whether they had BV or not, proceeded as normal through their pregnancy.  Women in both groups had their vaginal microbiomes sampled at various time points throughout the pregnancy. The first group would have their BV status verified, and placed on antibiotics. In both groups, approximately 10% of the women had preterm birth at around 30 weeks gestational age.  There was no significant difference in these rates between the two groups, meaning that administration of antibiotics did not appear to prevent preterm birth.  Even though the antibiotics did not prevent preterm birth, the researchers noted that regardless of group, women who entered preterm birth did have abnormal vaginal flora compared to women who went full term, supporting the notion that BV is highly correlated with preterm birth.  They noted that many of the women who entered preterm labor did not have BV at the initial time of screening, but acquired BV at some point during pregnancy. 

This paper supports the idea that BV may cause preterm birth, however it cannot recommend universal screening for BV in pregnant women for two reasons.  First, the antibiotics did not appear to affect the rates of preterm birth, and second many of the women who had preterm birth only had abnormal flora after initial screening.  Perhaps a better strategy would be to constantly monitor BV status throughout pregnancy.  In addition, there will soon be healthier and more effective methods to treat BV than antibiotics, which are only shown to have a transient effect on BV and disrupt the rest of the microbiome.

Gut bacteria may help prevent asthma in children

The world has seen an explosive rise in asthma over the past three decades. Such a rise in prevalence cannot be only a result of genetic variation and leads us to believe that environmental factors play an important role in this change. There are several possible explanations for this including what we call the “hygiene hypothesis”, or the idea that we now live in an environment that is too clean and we are no longer exposed to the bacteria and germs that earlier generations were exposed to. Another possible explanation is as the world changes and becomes more modern, these environmental changes are affecting our microbiome and the “normal” microbiome is shifting to a new normal.

To better understand why some children are at high risk for becoming asthmatic, scientists in Canada studied the microbiome of 319 children in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. They sequenced fecal samples from the children and found that 4 groups of bacteria that were decreased in prevalence compared to the children without asthma. Bacteria from the genus Lachnospira, Veillonella, Faecalibacterium, and Rothia (FLVR) were at lower levels after 3 months for the children at high risk for asthma however over time, this leveled out and was similar to the children not at risk for asthma.

The study did not identify what exactly caused these differences as there could be several reasons for these differences including antibiotic use, the method in which the child was delivered either vaginally or by C-section, and if the child was breastfed or not. It is also possible and maybe even likely that some of the mother’s behaviors during the pregnancy such as diet could play an important role in the early development of the child’s microbiome.

The next obvious question is what can we do about this? Does this mean that we can now treat children that are deficient of these bacteria and they won’t get asthma? While it sounds simple, we don’t yet know too much about these bacteria and it will be important to better understand the impact his would have on the rest of development. Promising results from this study did show that when mice with low levels of FLVR were treated with probiotic samples of the bacteria, it protected them from getting asthma.

This is a very exciting study that may lead to new diagnostics for asthma and with more research and understanding, allow us to prevent the disease from developing.