Bugs To Drugs: Can Probiotics Treat Depression?

Depression is a debilitating mental illness that affects up to 15 million Americans in the US alone, yet we are far from understanding the root cause. Multiple genes have been associated with depression, but whether these genes produce symptoms depends on the individual’s environment. New research is showing that one of the biggest environmental factors impinging on mental health comes from within.

Our body is home to trillions of microscopic creatures, mostly bacteria, which are collectively referred to as our microbiota. As unsettling as that may sound, these microbes are not necessarily the kind we want to evict from our body. The bacteria dwelling within our gut serve many important functions; for example, they help digestion, produce vitamins, and keep other types of microbes that cause disease at bay.

Our microbial inhabitants bring countless additional genes into our body called the “microbiome.” These microbial genes can be considered an extension of our own DNA – a so-called “second genome.” In other words, your body is not only influenced by the genes in your DNA, but it can also be affected by genes carried by your microbiota. These microbial genes not only affect physical health, but may also alter your mood and personality.

It is convenient to refer to species of our microbiota as "good" or "bad", but in reality they are neither. There are bacteria that can cause serious disease, like C-diff, but usually only after the microbiota has been disrupted (e.g. after prolonged antibiotic treatment). Likewise, "good" bacteria like E. coli can cause life-threatening disease under the right circumstances.  

Our microbiota help produce surprising amounts of neurotransmitters – chemicals that function in brain signaling. When laboratories produce “germ-free” mice by raising them in sterile environments, the mice exhibit strange neurological issues. Lacking their gut microbiota, germ-free mice do not respond to stress properly. These studies have given rise to the concept of the “gut-brain” axis, a conduit of biochemical communication between these organ systems. Such an axis exists in people too, as researchers have noted a strong correlation between intestinal problems and mental illness. For example, anxiety and depressive disorders are associated with both irritable bowel syndrome and ulcerative colitis.

A study by Ioana A. Marin and colleagues at the University of Virginia, published on March 7, 2017 in Scientific Reports, provides new evidence that intestinal bacteria influence mental disorders such as depression. In this experiment, mice were subjected to unpredictable chronic mild stress (UCMS), which involves strobe lights, irritating noise, cage tilting, and crowded conditions. Kind of like being shoved into noxious nightclubs against your will at random times throughout the day.

Unlike Disco Mickey, laboratory mice become stressed out when subjected to stimuli that resemble your average nightclub.

Over time, mice subjected to UCMS begin to show symptoms that resemble depression in humans. The researchers look for “despair behavior,” which can be detected in a number of ways. In this study, the mice were placed in a tub of water to evaluate despair behavior. Unstressed mice quickly swam to a platform and escaped, but the stressed mice did not make a strong effort to escape and had to be rescued from the tub.

The researchers then compared what the intestinal microbiome looked like in stressed versus unstressed mice. The different species of bacteria comprising the microbiota can be determined by sequencing the DNA in mouse droppings. Each species has a signature DNA sequence that serves as an identifier for that type of bacteria.

The results showed that stress altered the mouse microbiome by reducing a type of bacteria called Lactobacillus. It might have occurred to you that stress could have simply changed the eating habits of the mice, which in turn would affect the composition of the microbiome, but the researchers did not observe any change in eating habits or weight of the stressed mice. Furthermore, when they administered Lactobacillus as a probiotic, the symptoms of depression improved.

Why would stress cause changes in the microbiome? No one knows for sure, but this could be a result of altered brain chemistry making the gut less hospitable to some bacteria. Researchers also noted that intestinal physiology was altered in the stressed animals, which could have played a role in microbiota changes.

When someone consumes a probiotic they are ingesting live bacteria. That concept should no longer gross you out. Probiotics include the so-called "good" bacteria that have been shown to confer health benefits in some studies. These bacteria can be delivered into your body in numerous ways, including food (like yogurt) or pills.  

Does this mean you should rush out to purchase probiotics to battle depression? There are important caveats to studies like this that should be considered. The study was performed in a mouse model of depression, which may not fully represent the condition in humans. The microbiome of controlled laboratory animals is more uniform than humans, who tend to have vastly different bacteria in their guts depending on such things as diet, geography, illness, and age.

However, a 2016 meta-analysis (a study of studies) concluded that “probiotics were associated with a significant reduction in depression [in humans], underscoring the need for additional research on this potential preventive strategy for depression.” While that sounds encouraging, we are far from understanding how certain bacteria may ameliorate depression and whether this affect holds up in diverse patient populations. Probiotics certainly should not replace the more rigorously established treatments for depression recommended by health professionals.

Bill Sullivan is a professor at the Indiana University School of Medicine. Follow him on Twitter @wjsullivan.

A Literal "Beer Gut"

Imagine you are a police officer and suddenly the car in front of you is beginning to drive erratically. You dismiss it at first, thinking the driver was just momentarily distracted. Then he starts swerving left and right, slowing down and then speeding up. You take a closer look inside the car. Looks like a family of four. Presumably the wife in the passenger seat, two kids in the back. The kids are behaving. He's not using his phone. The driver doesn't look distracted.

After the man nearly runs the car up on the sidewalk, you flash your lights. He pulls over without incident and appears cooperative, almost happy. Carefree, in fact.

"What's the problem, officer?" His words are slurred, virtually confirming your suspicion. This guy is three sheets to the wind (incidentally, that is an old maritime phase referring to when fasteners holding the sails became loose and control of the boat was lost).

"Have you been drinking tonight, sir?"

"Nope! Just had some spaghetti and breadsticks. Hey, I like your badge. Shiny! Can I hold your gun?" He becomes giddy with laughter.

You look over at the woman in the passenger seat. "It's true, officer. He never drinks! He gets this way after having pasta sometimes. I told him not to have seconds. How about I drive instead and we just forget the whole thing?"

Sounds like a family trying to put one over on the police, but there really is a condition called "auto-brewery syndrome" or "gut fermentation syndrome". People experience this rare condition when microbes turn the belly into a brewery. 

People with the rare condition known as "auto-brewery syndrome" can turn this carbohydrate-rich plate of pasta into enough alcohol to make them feel drunk.

A woman recently diagnosed with the syndrome had her DUI charges dismissed. She was monitored for a twelve hour period, taking a breathalyzer test every few hours. Despite having no alcohol whatsoever, her blood alcohol content rose steadily throughout the day, reaching to four times the legal limit by the end of the period.

As we've mentioned in previous articles, our body is home to trillions of microbes that collectively made up our microbiome. These microbes are largely intestinal bacteria and fungi. They perform indispensable tasks for us, such as helping to produce neurotransmitters, vitamins, and immune regulators. But on very rare occasions, certain yeasts in our gut, namely Saccharomyces cerevisiae or Candida albicans, can grow out of control and start converting carbohydrates into alcohol.

People with auto-brewery syndrome quite literally have a "beer gut". The yeast in their body can produce alcohol without the person taking a sip of booze. Some people learn to adapt and live with this higher-than-average blood alcohol content, much like anyone who builds up a tolerance to alcohol by increasing hepatic (liver) metabolism. Unbeknownst to them, some people have been living with the condition for years.

People with auto-brewery syndrome actually make alcohol in their intestines where the fungi live. So feeding them hops and tapping their stomach is not going to provide you and your friends with a ready source of free beer.

It is not known why the yeast can take such a foothold in the gut of these patients. One documented case report suggests that a course of antibiotics, which wipe out a lot of "friendly" gut bacteria but don't hurt yeast, can create an environment in the intestine that favors growth of the yeast. With the bacteria depleted, there is less competition for nutrients, so the yeast can grow out of control. Some researchers have argued that overgrowth of fungi is not to blame, but rather the patient may have genetic defects that prevent the liver from metabolizing the minute, normal levels of alcohol that may ferment in the gut. These two possibilities are not mutually exclusive.

Yeast are a type of fungi that have enzymes able to convert sugars like glucose into pyruvate, ethanol (alcohol), and carbon dioxide as waste products. One organism's waste is another organism's treasure!

In addition to creating obvious hazards and embarrassing situations, auto-brewery syndrome causes bad hangovers as well. Is there any way to alleviate this problem? One report stated that a 10 week course of anti-fungal drugs and probiotics, the latter of which aim to replenish the gut with bacteria that belong there, eliminated the condition from the patient.

So if you see someone acting like a belligerent fool for no logical reason...well, most likely they're just being a jerk. But there is a small chance that they have auto-brewery syndrome and deserve your compassion rather than condemnation.

Contributed by:  Bill Sullivan
Follow Bill on Twitter.

Cordell, B., & McCarthy, J. (2013). A Case Study of Gut Fermentation Syndrome (Auto-Brewery) with Saccharomyces cerevisiae as the Causative Organism International Journal of Clinical Medicine, 04 (07), 309-312 DOI: 10.4236/ijcm.2013.47054 

Living Off Nothing But Coffee

Can you imagine living off nothing but coffee? Some of us probably feel like we do at times, if not for the taste then for the buzz the caffeine brings. Caffeine makes us feel more alert because it structurally resembles a molecule called adenosine.

Caffeine and adenosine are like brothers from another mother.

 Adenosine accumulates in our brain the longer we stay awake, binding to its receptors to induce that sleepy feeling we all get after a long day. It is the body’s way of signaling to the brain that it has had enough and needs to shut down for a while. If you disagree with your body, the ingestion of caffeine can help. Due to their structural similarity, caffeine competes with adenosine for binding to adenosine receptors; however, adenosine receptors do not execute the signal to shut down when bound to caffeine. In other words, the body is trying to throw a pass to sleep but caffeine blocks the receiver.

Some people can’t get to their happy place without a cup of joe in the morning. By the way, the term “cup of joe” is likely to have originated from “cup of jamoke” - “jamoke” being a combination of locales noted for their coffee goodness, “Java” and “Mocha”.

But that’s not all. Caffeine also ramps up adrenaline production, which increases your heart and breathing rates, and primes your brain and muscles for action. You feel a boost from coffee because the caffeine blocks the signal to sleep and fools your body into thinking it is under attack.

 

Like other drugs, people can build up a tolerance to caffeine, requiring more and more of the drug just to achieve the sensation of that original buzz. And the road to addiction is a short one, indeed. People love their coffee so much that the threat of a shortage can send them into a panic, which is perfectly captured in this scene from Airplane II.

 

How much coffee can people safely consume? According to the FDA, 400 mg (4 cups of brewed coffee) per day appears to be safe for most healthy adults. While it is estimated to take about 140 cups (8 oz size) of coffee to kill, you can get there a lot quicker with pure caffeine powder. A single tablespoon can be lethal, prompting the FDA to issue this warning to consumers.

But there is a creature on Earth that can tolerate much, much more. In fact, it eats coffee beans for breakfast. And lunch. And dinner. And everything in-between. Amazingly, the coffee berry borer eats nothing but coffee beans!

The coffee berry borer is a small but devastating beetle that lays waste to coffee crops. It subsists solely on coffee, capable of drinking any Starbucks junkie under the table.

Scientists have recently discovered how the coffee berry pest can tolerate toxic levels of caffeine. Do they possess a special gene that can detoxify caffeine? Do they have receptors that don’t bind caffeine? No…evidently, the answer does not lie in the genome of the beetle, but in its gut.

 

Like most other living creatures, the coffee berry borer houses a microbiome in its intestinal system. Several species of bacteria, such as Pseudomonas fulva, that reside in the gut of coffee berry borers are wizards at breaking down caffeine. The gut bacteria from coffee berry borers found around the world were put into culture medium containing caffeine as the primary nutrient so researchers could identify which species grew the best in this condition. P. fulva was the most common; subsequently, this bacterial species was found to carry a gene known to degrade caffeine.

To further test this hypothesis, researchers gave the beetles antibiotics to deplete their intestinal microbiome. Beetles without their gut bacteria lost the ability to break down caffeine. When fed some P. fulva before their coffee bean diet, the beetles excreted no caffeine, indicating that they were able to detoxify it once again.

Assuming no adverse effects, ingestion of P. fulva might help humans break down caffeine. A better alternative to decaf?

The scientists speculate that altering the beetle’s microbiome might provide a new approach in the battle against this pest. However, antibiotics are a precious commodity in treating human disease, so this could be a reckless idea as the introduction of antibiotics into the field has the potential of generating resistant bacteria.

From an evolutionary perspective, the study serves as an example of how organisms can adapt to a new niche without genetic modification. By acquiring specific types of bacterial symbionts, the coffee berry borer is uniquely able to live off nothing but coffee.

In the video below, you can learn more about this research and similar studies being performed at Lawrence Berkeley National Laboratory:
 

 

Contributed by:  Bill Sullivan

Follow Bill on Twitter.

See the news release at ScienceDaily.
 

Ceja-Navarro, J., Vega, F., Karaoz, U., Hao, Z., Jenkins, S., Lim, H., Kosina, P., Infante, F., Northen, T., & Brodie, E. (2015). Gut microbiota mediate caffeine detoxification in the primary insect pest of coffee Nature Communications, 6 DOI: 10.1038/ncomms8618

Complexities Of Allergic Disease

Last time we discussed the main players involved in the immune response to allergens, in the reaction called Type I hypersensitivity. We know that hay fever and other allergies are a result of atopy, the genetic predisposition to mount excessive IgE-mediated immune responses. Atopy is derived from a Greek word that means unusual or out-of-place. Although the immune overreaction is indeed out of place, the prevalence of allergic disease in society is not. Approximately 25% of the world’s population suffers from allergies, making it one of the most common chronic diseases. Unfortunately, this number is actually increasing, so researchers are trying to understand the factors that contribute to allergic disease.

Advances in genome sequencing and the completion of the Human Genome Project have allowed scientists to use genome-wide association studies (GWAS) in attempts to identify certain disease-causing genes. While many candidate genes have been described for hay fever, each search appears to reveal additional candidates. It has become clear that hay fever is a complex disease, driven by genetics and environmental exposures, both pre- and postnatal. Because of this complexity, atopy does not follow a Mendelian model of inheritance, like eye or hair color.

To perform GWAS, researchers collect blood or tissue samples from individuals with the disease of interest and from symptom-free control subjects. In many allergy studies, the controls are within the same family, which helps tease apart genetic differences that might actually contribute to disease. This is helpful because 300,000 to 1 million changes in the DNA are tested. These changes called single nucleotide polymorphisms (SNPs), a type of mutation that indicates a single change in the DNA base pair. If certain SNPs appear more frequently in the individuals with the disease, they are said to be associated with that disease. Additional DNA sequencing is performed to determine the exact change, and then ideally that SNP is studied in the lab to understand the consequence of the change on cellular function.

Sometimes mutations give super-human agility, strength, or intelligence. Other times they set us up to have wild and potentially unnecessary symptoms like Beast’s blue fur. Or perhaps equally annoying, the itchy watery eyes, nose, and throat from hay fever that come from a super-human response to harmless allergens.

A few notable candidate genes have been identified as associated with hay fever or with higher levels of circulating IgE antibodies, as we learned is a hallmark of atopy. Cytokines are the main signaling molecules that trigger activation of B cells to produce IgE antibodies, and not surprisingly, people with hay fever have mutations in genes that encode for cytokines or regulate their production. Also associated with hay fever are changes that enhance and stabilize the IgE receptor on mast cells and basophils, contributing to more intense symptoms. Genes responsible for airway smooth muscle contractions, contributing to cough and wheeze, are also implicated. SNPs have been identified in the genes encoding chemical mediators that cause ongoing symptoms such as leukotrienes, and in the specialized effector cells involved later in allergic inflammation response, such as eosinophils.

These are just a few examples of genes; dozens of others are being studied to learn exactly how they contribute to hay fever. Furthermore, some genes are only associated with allergies in the context of specific environments, further complicating the identification of true disease-causing genes. One clue that environmental factors influence allergies comes from studies of twins. Twin studies have shown that between monozygotic (identical) twins there is on average a 65% (range, 42-82%) chance that if one twin has allergies, the other will also have them. Between dizygotic (fraternal) twins, there is on average a 33% concordance rate (range 15-52%).

Some differences in twins are obvious, but other differences like allergies require epidemiological studies to tease apart.

The “hygiene hypothesis,” proposed by D. Strachan in 1989, became a popular basis to explore the increased incidence in allergic disease. Strachan observed that increased family size was associated with lower rate of allergies. He proposed that if allergies were prevented by early childhood infections, unhygienic contact with older siblings may protect against hay fever. Immune responses to pathogens like bacteria and viruses use a T-helper 1 (Th1) cell response. We know that Type I hypersensitivity reactions are mediated by Th2 cells’ stimulation of B cells to produce IgE antibodies. So the theory is that early childhood infections bias the immune system towards a Th1 response and suppress Th2 responses.

If Strachan’s hypothesis is correct, the Bates family should be allergen-free.

Strachan performed additional epidemiological studies to investigate the hypothesis that infections and larger family size protect against hay fever. He published a report in 2000 stating that decreases in family size do not appear to explain the increased incidence of allergies. Many additional studies looking into the protective effects of childhood infections have shown inconsistent results; some show a “protective” effect whereas others show either no association or early childhood infections correlated with development of allergies.

The “hygiene hypothesis” developed into a much broader “microflora hypothesis” which proposes that urbanization and a Western lifestyle limits our exposure to bacteria, viruses and parasites in general. Clean water, increased Cesarean sections, reduction in breastfeeding, increased antibiotic and antibacterial use, and reduced exposure to farm animals have limited our exposure to our microbial “old friends”. According to this idea, these “old friends” have evolved with us to the point where we require them for proper immune function.

 

“The Wonder Years” cast knew that we get by with a little help from our friends.

The diversity of our microbiome is decreasing, which may have detrimental effects on general health and the efficiency of our immune system. W. Parker proposed the term “biome depletion” to describe this current phenomenon. A few recommendations can be found here to increase microbial diversity in the gut.

Just like the Biodome, our biomes are not closed systems and can let in and respond to passer-byers, for better or for worse. In the case of Pauly Shore, it’s always for the worse.

If there weren’t already enough factors to consider in development of allergies, let’s peel back another layer. In addition to acquiring genes and microbiota from mothers during birthing and breastfeeding, in utero we are largely influenced by our mother’s environment through epigenetics. We’ve discussed epigenetics previously; briefly, it describes changes in the DNA and DNA-associated structural proteins that act to turn genes on or off. Epigenetic regulation either gives a green light or red light to production of specific gene products, or can act as a volume knob to finally tune gene expression. The process is plastic, allowing our genes to respond to the present environment.

Upon conception, epigenetic reprogramming occurs in the zygote, like a reset button. However, some epigenetic marks remain and are inherited by the offspring. So before and largely during pregnancy, the mother encounters various environments and the body responds using epigenetics to regulate genes at the appropriate time. These changes occur in the embryo or fetus as well, as a way to prime the baby for its eventual environment.

There is evidence that the immune system is under epigenetic regulation. At birth, atopy-prone infants tend to have diminished Th1 cell responses, thought to be influenced by the maternal environment. Additionally, maternal diet, microbial exposure, and smoking can influence epigenetic regulation of key genes involved in immune regulation and allergy development.

While there is no consensus on allergy prevention, there are many options for treatment of allergies, which will be discussed in the final allergy article in this series – coming soon!

Contributed by:  Julia van Rensburg, Ph.D.

Follow Julia on Twitter.

Dávila I, Mullol J, Ferrer M, Bartra J, del Cuvillo A, Montoro J, Jáuregui I, Sastre J, & Valero A (2009). Genetic aspects of allergic rhinitis. Journal of investigational allergology & clinical immunology, 19 Suppl 1, 25-31 PMID: 19476051

Grammatikos AP (2008). The genetic and environmental basis of atopic diseases. Annals of medicine, 40 (7), 482-95 PMID: 18608118

Strachan DP (2000). Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax, 55 Suppl 1 PMID: 10943631

Parker W (2014). The "hygiene hypothesis" for allergic disease is a misnomer. BMJ (Clinical research ed.), 348 PMID: 25161287

Martino D, & Prescott S (2011). Epigenetics and prenatal influences on asthma and allergic airways disease. Chest, 139 (3), 640-7 PMID: 21362650

Pull Up A Stool And Let's Talk About Your Microbiome

A medical case report recently made headlines supporting the notion that the bacteria inside our gut have something to do with the size of our gut.

Clostridium is a nasty strain of bacteria that is resistant to many antibiotics. Normally, the many other species of bacteria in the gut keep Clostridium in check, but when those friendly bacteria are wiped out during antibiotic therapy, Clostridium can thrive and produce severe inflammation (colitis) and diarrhea. This can develop into a serious illness that claims the lives of 14,000 Americans every year.

A novel way to treat this condition is through use of fecal microbiota transplant (FMT). In other words, the patient ingests the intestinal bacteria from a healthy person to replenish their own stock and get Clostridium back under control. We will leave it to your imagination as to how doctors collect the good bacteria, but let's just say you can make some decent money if you're willing and able to donate. Thankfully for patients, FMT is available in pill form.

As unappealing as it sounds, fecal transplants - which repopulate intestinal bacteria in the recipient - are proving to be very effective in treating some serious ailments. 

As reported recently, a young woman with a stable weight of ~130 pounds had to undergo FMT to fight a Clostridium infection. The good news is that she beat the infection, but the bad news is that she gained 34 pounds in 16 months, classifying her as obese with a BMI of 33. Even more alarming is that she could not lose weight despite being on a supervised liquid diet and exercise program. The donor for the FMT (her teen daughter) was overweight, but otherwise in good health, so doctors are now recommending that FMT donors be of normal weight.

In light of this news, here's a beginner's guide to the tiny creatures calling you "home"...

You are not just a person – you are an ecosystem. Your body is home to trillions of microscopic critters, including viruses, bacteria, and fungi, living on or inside you. Collectively, these communities of microbes constitute what is called your “microbiome”.

And there are more of “them” than “you” – the number of microbes inhabiting your body is larger than the number of cells making up your body! To put this in perspective, it has been estimated that your microbiome weighs about 3 pounds. Good news if you’re on a diet – when you step on the scale tonight, feel free to subtract 3 pounds of stuff that isn’t “you” per se.

A new study concerning our microbiome seems to be coming out each week, so it is time we get to know our microbial roommates.

1. Where does your microbiome come from?

We are born virtually sterile, but quickly receive an infusion of bacteria from our mom, first through the birth canal and then through the milk. Over 900 species of bacteria have been found in breast milk, and these are the pioneers that settle into your gut, which appears to stabilize by the age of 3. Of potential interest are babies born by caesarean section or those who are fed formula instead of breast milk. Babies delivered via C-section do in fact have a different microbiome and may be at higher risk for certain types of allergies and obesity (more on this below). Our microbiome continues to receive fresh new imports as we move through, inhale, and ingest our environment.

How much of you is really you? There are more microbes in your body than the number of cells making up your body. We are just now beginning to appreciate the many things they do for us.

2. Your microbiome is like your own personal “germ cloud”.

You’ve probably noticed that everyone’s home smells a little different. Sometimes this is due to cooking, pets, or the amount of trash they let accumulate, but it is also due in part to the microbiome of the inhabitants. Researchers have found that you are surrounded by a “germ cloud”, and you leave pieces of your microbiome wherever you go like a trail of breadcrumbs. It might even be possible for police to use microbiomes to track people one day like they currently use fingerprints or DNA. In other words, you have a “microbiome fingerprint” that is left behind like a germ echo wherever you go.

This “germ cloud” may also explain how dogs can track people so easily. The byproducts generated by the millions of bacteria living on your skin are aromatic (odorous), producing a scent that is released into the air as you move. Animals with a keen sense of smell can get a whiff of these aromatic compounds and follow them to the source.

Speaking of “germ clouds”, if you ever wondered if it is possible to fart out germs, some brave scientists have sniffed out the answer to this question. You can read about the results here.

3. Antibiotics substantially alter your microbiome.

We take antibiotics to get rid of pathogenic bacteria that make us sick. The problem is they are not selective, so they destroy a lot of our friendly bacteria in addition to the bad guy. We need these friendly bacteria to do all sorts of things – to name just a few:  they help us digest food, make vitamins, and build anti-inflammatory compounds.

Another important thing our microbial friends do is keep infections in check. For example, yeast infections from pathogenic fungi can arise if good bacteria are not around competing for resources. And some bacteria, like the nasty Clostridium difficile, are naturally resistant to many antibiotics. When good bacteria are killed as collateral damage in an antibiotic treatment, the growth of Clostridium can run amok. These bacteria secrete a toxin that causes diarrhea and they can lead to a life-threatening superinfection in some patients.

4. Your microbiome may protect you from allergies or obesity.

Several recent studies have correlated unusual microbiome composition with the presence of certain allergies. Dr. Hans Bisgaard has shown that infants harboring fewer species of gut bacteria have an increased risk of developing certain allergies as they grow up. More recently, Dr. Catherine Nagler has shown that certain bacterial species offer protection from peanut allergies.

Dr. Martin Blaser has found that administration of penicillin to mice soon after birth altered their gut microbiome in such a way that it made them more prone to obesity as adults. Remarkably, the tendency to grow obese is transferrable to germ-free mice – in other words, by transplanting the microbes from the penicillin treated mice to normal mice made the normal mice more susceptible to weight gain.

Studies such as these make it tantalizing to speculate that we may be able to treat certain ailments in humans by altering our microbiome with specific probiotic regimens. Maybe they could even slip these bacteria into our peanut butter instead of deadly Salmonella.

5. How do scientists study the microbiome?

Advances in DNA sequencing have allowed scientists to rapidly map the genomes for many microbial species, which provides us with a “genomic fingerprint”. We can process samples swabbed from the skin or body cavities, or process stool samples, for DNA sequencing. Usually just sequencing the 16S ribosomal RNA gene is enough to distinguish one bacteria species from another.  

It should be mentioned that some scientists are issuing cautions about over-interpreting microbiome studies. Many of the studies altering the microbiome have been performed in mice, so it remains to be determined to what extent the findings can be extrapolated to humans. Furthermore, many of the methods used to alter the microbiome in lab animals do not faithfully mimic what humans do with antibiotics. For example, in some studies the investigators give large doses of antibiotics over unusually long periods of time to see an effect in lab animals, which does not equate to the typical dosing of antibiotics in humans. Finally, many of these studies are correlative and have not yet definitively demonstrated causation. There is a big difference between correlation and causation.

6. So should I take my microbiome into my own hands?

Much more research needs to be done to assess the true impact of the microbiome versus other factors that come into play, such as host genetics, diet, and the environment. It is argued that some microbiome studies are hyped up and way overblown. Long story short:  if you or your child becomes sick with an infectious agent, it is not wise to withhold antibiotic treatment out of fear that it will cause allergies or obesity. If you are overweight, a healthier diet and plenty of exercise is going to do much more than any probiotic pill. In fact, there is little evidence that the popular probiotics on the market do anything to remedy the wide-ranging health problems some claim to treat, although there is data showing potential benefit in treating some gastrointestinal maladies, especially acute diarrhea caused by rotavirus.

Go here to learn more about the NIH human microbiome project.

Contributed by:  Bill Sullivan, Ph.D.

Follow Bill on Twitter.

Lax S, Smith DP, Hampton-Marcell J, Owens SM, Handley KM, Scott NM, Gibbons SM, Larsen P, Shogan BD, Weiss S, Metcalf JL, Ursell LK, Vázquez-Baeza Y, Van Treuren W, Hasan NA, Gibson MK, Colwell R, Dantas G, Knight R, & Gilbert JA (2014). Longitudinal analysis of microbial interaction between humans and the indoor environment. Science (New York, N.Y.), 345 (6200), 1048-52 PMID: 25170151

Bisgaard, H., Li, N., Bonnelykke, K., Chawes, B., Skov, T., Paludan-Müller, G., Stokholm, J., Smith, B., & Krogfelt, K. (2011). Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age Journal of Allergy and Clinical Immunology, 128 (3), 646-65200000 DOI: 10.1016/j.jaci.2011.04.060

Cox, L., Yamanishi, S., Sohn, J., Alekseyenko, A., Leung, J., Cho, I., Kim, S., Li, H., Gao, Z., Mahana, D., Zárate Rodriguez, J., Rogers, A., Robine, N., Loke, P., & Blaser, M. (2014). Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences Cell, 158 (4), 705-721 DOI: 10.1016/j.cell.2014.05.052

Stefka, A., Feehley, T., Tripathi, P., Qiu, J., McCoy, K., Mazmanian, S., Tjota, M., Seo, G., Cao, S., Theriault, B., Antonopoulos, D., Zhou, L., Chang, E., Fu, Y., & Nagler, C. (2014). Commensal bacteria protect against food allergen sensitization Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1412008111

Williams NT (2010). Probiotics. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 67 (6), 449-58 PMID: 20208051

Alang, N., & Kelly, C. (2015). Weight Gain After Fecal Microbiota Transplantation Open Forum Infectious Diseases, 2 (1) DOI: 10.1093/ofid/ofv004

Attack Of The Germs!

No one likes being sick, especially with the flu. The body aches, the fevers, and the congestion all leave us desperate for ways to end the misery. Indeed, it’s growing increasingly hard to ignore the commercials telling us to stock up on flu-fighting products, like disinfectants and hand sanitizers. But how much do these items really help you avoid becoming the flu’s next victim, and do they have other consequences that we should be aware of?

Let’s first take a look at how many of the popular disinfectants work. Cleaners like Lysol have different types of salts in them that kill germs by disrupting important protein interactions, which causes the pathogen to stop functioning normally. These salts can also work by breaking up the membrane that surrounds bacteria and some viruses, essentially breaking open the pathogen and causing everything inside it to leak out. In both of these cases, the germs stop growing or are killed altogether.

Alcohol-based hand sanitizers work in a similar manner. At concentrations of at least 60%, ethyl alcohol (or ethanol) is effective at killing some viruses, including influenza viruses. Ethanol works by changing the shape of proteins, and therefore interferes with their ability to properly interact with other proteins. Ethanol can also disrupt membranes.

 

Image of Influenza virus from the CDC highlighting proteins on the outer surface that help the virus infect cells, and the viral genome located inside.

While killing off the germs that can make us sick sounds like a good way to stay healthy, the problem with using disinfectants and sanitizers to do this is that these products kill nearly all of the microbes in our environment. While there are many microbes that make us sick, there are also many that we need to help keep us healthy. If we kill those microbes off too, then we may put ourselves at risk for developing other health problems. 

On and within our bodies live millions and millions of good microbes that do things from helping us digest food, to helping keep bad microbes out of our bodies. These good microbes encompass the population known as the microbiome. The microbiome populations shift depending on the location of the body. For example, we have good bacteria that live on our skin, the population of which differs from the population of good bacteria that live in our digestive tracts. There is increasing interest in exploring the functions of the different microbiome populations, and many studies are showing that the microbiome has important roles in keeping us healthy. For example, it is thought that irregularities in the gut microbiome population may have a role in some inflammatory bowel diseases like Crohn’s disease and ulcerative colitis. It is possible that killing off the beneficial microbes in and on our bodies counteracts any good effect from killing off germs.

 

Keeping our good microbes around is only part of the story. According to the CDC, we are currently on the brink of a public health crisis due to the increasing numbers of microbes that are becoming resistant to common antibiotics. Due to our overuse and misuse of antibiotics, we have created strains of bacteria that are no longer susceptible, or able to be killed, by standard treatments. As bacteria populations are constantly exposed to antibiotics, many of those bacteria will be killed because they are sensitive to the antibiotic, but there will be some that are naturally able to withstand the actions of the antibiotic. Eventually, the population of bacteria that was initially a mix of sensitive and resistant will transition to a population of bacteria that is completely resistant, as all of the susceptible bacteria are killed off. What is the impact on us? In 2013, the CDC reported that at least 2 million people in the United States become infected with antibiotic-resistant bacteria, and that at least 23,000 of these people die from their infections.

Perhaps the most well-known case is MRSA, or methicillin-resistant Staphylococcus aureus. Staph bacteria are common and normally cause minor skin infections; however, MRSA has been highlighted in the media several times over recent years due to the outbreaks of invasive infections it has caused due to its resistance to standard antibiotics. MRSA is but one example of the bacterial strains that develop resistance to antibiotics due to constant exposure to them.

As we continue the cycle of overuse and misuse of antibiotics, we eventually will find ourselves at a point where no antibiotics will be effective against bacterial pathogens. Many public health experts suspect that point is near. There is reason to believe that constant use of disinfectants will eventually lead to the development of germs that are resistant to those disinfectants, just as we see happening with bacteria and antibiotics.

So how do we keep ourselves healthy without potentially setting ourselves up for other health problems later? We can start by limiting our use of disinfectants, and go back to simpler, tried-and-true methods of preventing the spread of communicable diseases. Despite the popularity of disinfectants and hand sanitizers, the CDC still maintains that hand-washing is one of the best ways to avoid spreading and catching viral and bacterial infections from others. Wash your hands before you eat, and avoid touching your hands to your eyes and nose.  If you are sick, do your best to sneeze or cough into the crook of your elbow (i.e., do the “Dracula sneeze”) rather than into your hands, and wash your hands frequently to avoid spreading your germs to others.

 

Of course, use soap that does not contain antimicrobial additives, like triclosan, to avoid encouraging the development of strains resistant to this compound. Soap is a potent killer of germs all by itself - it does not need supplemental antibiotics. While some companies are moving away from including triclosan, it is still present in many products, so be sure to check your labels.

Disinfectants have their place; they’re good for cleaning up food preparation areas that have come into contact with raw meat, for example. And, in times when you’re without clean water and soap, hand sanitizer can be a great tool for keeping your hands clean. But as with most things in life, these items should be used with care and arguably in balance with other washing methods in order to avoid creating greater problems down the line.

Contributed by:  Kelly Hallstrom
Visit Kelly’s blog, You Don’t Have To Be A Rocket Scientist
Follow Kelly on Twitter.

 

CDC Threat Report on Drug-Resistant Bacteria:

http://www.cdc.gov/drugresistance/threat-report-2013/

CDC and hand washing:

http://www.cdc.gov/handwashing/

 

Greenblum, S., Turnbaugh, P., & Borenstein, E. (2011). Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease Proceedings of the National Academy of Sciences, 109 (2), 594-599 DOI: 10.1073/pnas.1116053109