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
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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 

Potential Benefits of Thumb-sucking and Nail-biting in a Too-Clean World

In a world of Lysol and Purell, it's easy to become all-consumed with keeping clean. And why not? We're on the go more than ever now:  we're working longer hours (1, 2), spending more time commuting (3), and we’re under constant pressure to keep up to date on all the available social media networks (4). No one has time to be slowed down with the flu or a cold. So we dab on a little hand sanitizer before we eat, clean our houses regularly with bleach-containing products, and hold our breath when someone sneezes in a crowded elevator (or maybe that's just me).

But is there such a thing as being too clean? Researchers who are focused on testing this so-called "hygiene hypothesis" think there may be.

 

The hygiene hypothesis proposes that living in a germ-free world is disadvantageous to our health. Studies testing the hygiene hypothesis have shown correlations between our squeaky-clean developed societies and increases in allergic conditions, compared to developing societies lacking modern infrastructures that support public health (5, 6). Some studies even point to differences in the levels of allergic conditions in cities versus rural towns within the same country (7). While such studies only suggest correlations, and don't definitively show clean environments cause a predisposition to allergies, their findings are worth considering.

While the biological explanation for the hygiene hypothesis is still being studied, evidence from such studies so far suggests that when our immune systems aren't regularly challenged by germs normally present in the environments we've been co-evolving with for millennia, the result is an immune system that is predisposed to allergic reactions. Our immune systems rely on a series of specialized cells programmed and primed to respond to different pathogenic and environmental challenges in a coordinated fashion:  for example, some cells respond to bacteria and viruses while others respond to parasites. Researchers investigating biological explanations for the hygiene hypothesis have proposed that a lack of exposure to bacteria and viruses in childhood causes a shift in the population of immune cells away from cells primed and ready to attack those germs and instead toward a population of cells programed to respond to allergic stimuli (6).

Of course being clean is a good thing. An awareness of how diseases spread and how to take precautions against them is one of the reasons why modern society has been able to flourish. Hand washing and sterilization techniques introduced in the 1800s by Dr. Ignaz Semmelweis dramatically reduced a common cause of death in maternity wards (9). Modern epidemiology enables us to learn and track how certain diseases can be spread (including the recent outbreak of E. coli in flour) so we can take preventative measures to avoid further spread of diseases. We're careful to cook our food thoroughly to avoid food borne illnesses like salmonellosis. All of these behaviors protect us from unwanted illnesses, and allow us to carry on with our lives. While we certainly don't want to undo all of the advances we've made in limiting the spread of disease, evidence suggests that there needs to be a balance between being too dirty and too clean.

A line of souvenirs at Disney parks last summer included hand sanitizers featuring popular kids characters. Image from https://disneyparks.disney.go.com/blog/2015/08/summer-of-souvenirs-continues-with-new-items-at-disney-parks/

For example, it was recently published in the journal Pediatrics (8) that thumb-sucking and nail-biting, generally thought of as being unsanitary, may help children avoid developing environmental allergies. The results came out of the Dunedin Multidisciplinary Study, in which researchers followed over 1,000 children born in Dunedin, New Zealand between 1972 and 1973 throughout adulthood. For this particular question, children were first examined at ages 5, 7, 9, and 11 and then tested for certain allergies at 13 and 32 years of age. The researchers conducting this study, Stephanie Lynch and Dr. Robert Hancox (from the University of Otago, New Zealand), and Dr. Malcolm Sears (McMaster University and St Joseph’s Healthcare, Ontario, Canada), found that the individuals who had been frequent thumb-suckers or nail-biters as children tested positive for allergic sensitivities less often than those who had not frequently engaged in those habits. More specifically, the researchers report that 49% of participants who had not been frequent thumb-suckers or nail-biters had positivity allergy tests, whereas only 31% of participants who had sucked their thumbs and bit their nails as young children had positive allergy tests. 

Granted, this is only one study and it's still probably not a good idea to advocate for children keeping their dirty hands in their mouths all of the time. After all, no one wants their child to be sick. But perhaps thumb-sucking is one thing parents don't have to worry about so much after all. Perhaps instead, we can trust that our bodies are designed to deal with those little germ and dirt exposures, and maybe even benefit from them in the long run.

http://peanuts.wikia.com/wiki/%22Pig-Pen%22

Contributed by:  Kelly Hallstrom

Follow Kelly on Twitter.

1. http://abcnews.go.com/US/story?id=93604&page=1

2. https://www.theguardian.com/business/2016/mar/27/britons-working-longer-hours-with-no-gain-in-productivity-study-finds

3. https://www.washingtonpost.com/news/wonk/wp/2016/02/25/how-much-of-your-life-youre-wasting-on-your-commute/

4. http://www.dummies.com/how-to/content/ways-to-stay-uptodate-with-social-media-changes.html

5. http://www.ncbi.nlm.nih.gov/pubmed/9643741

6. http://www.ncbi.nlm.nih.gov/pubmed/11964470

7. http://www.ncbi.nlm.nih.gov/pubmed/9228959

8. http://pediatrics.aappublications.org/content/early/2016/07/07/peds.2016-0443

9. http://www.npr.org/sections/health-shots/2015/01/12/375663920/the-doctor-who-championed-hand-washing-and-saved-women-s-lives

Mmmm…Raw Cookie D’oh!

For several years now, the government has told Americans to put down the tube of raw cookie dough and step away. New warnings about the harrowing dangers of cookie dough were announced by the FDA last week, right before our 4^th of July holiday. Seriously? You’ve been eating the stuff ever since your BFF started dating your ex in high school. What’s the big deal?

Where did things start to go wrong for Barney? Could it have been the raw cookie dough?

In this crazy, hustle and bustle world, who has the time to wait for the cookies to be cooked? Raw cookie dough allows you to savor all of the yummy cookie goodness without the grueling task of popping them into the oven and waiting 10 minutes, which feels like an eternity when you need your sugar fix. And then there’s the mess to clean up…who needs that?

So you defiantly crack open that tube and bury your face in the heavenly Play-Doh-like substance – nom nom. A few hours later, as you rest in content satisfaction on the couch, you begin to feel a great disturbance in The Force. An abrupt gurgle begins to percolate in your gut. Your stomach makes a demonic growl. Visions of volcanic eruptions suddenly waft through your woozy head. The horrific bout of bloody diarrhea that follows might be enough to convince you to listen to those pesky scientists at the FDA from now on. The intestinal apocalypse you experience may even have you wishing for death, but don’t do so lightly. Raw cookie dough has been known to kill.

Linda Rivera died in 2013, a victim of eating a few spoonfuls of raw cookie dough. Over 70 other people were sickened during this outbreak, which started in 2009 and affected mostly teenage girls and children.

How could something that tastes so good be so bad for you? Your first instinct might be the raw eggs in the dough, which could be contaminated with a common food poisoning bacterium, Salmonella. While this is indeed possible, the latest round of scares stem from flour contaminated with a particularly nasty strain of the bacterium Escherichia coli (E. coli). Shiga toxin-producing E. coli O121 has been identified as the culprit behind a massive recall of contaminated flour made by General Mills. Most E. coli strains are harmless, but this one is so not harmless.

Now you might be wondering:  how does E. coli, a bacterial species that inhabits the gut, get into flour? Flour comes from grain grown in fields where animals may do their business - not the kind of "chocolate chips" you want in your cookie dough! But the grain is not normally sterilized because manufacturers assume that people would actually cook the items made from that flour, which kills the E. coli. However, some people just want the “goods” and not the “baked” part.

The Shiga toxin produced by this type of E. coli is the cause for the alarm – these are proteins made by the bacteria that can bind to receptors on our cells, particularly in the intestine and the kidney, which is why people experience bloody diarrhea and renal failure when infected. Once inside our cells, the Shiga toxin can bind to our ribosomes, which make our cellular proteins. When our cells can’t make proteins, they eventually die.

E. coli bacteria are kind of scruffy-looking, but those “hairs” are actually flagella the bacterium uses to get around. About 10,000 of these can fit on the head of a pin. It only takes 10 of the more virulent strains to make you seriously ill.

Over 40 people have been sickened from the recent outbreak, almost a baker's dozen requiring hospitalization. There have been no deaths to date, and deaths from cookie dough remain extremely rare…but it has happened and is a most unpleasant way to leave the world. So cook your cookies or risk tossing them later.

The FDA also warned that pizza dough, “play clay” made from dough, or “flour crafts” that kids sometimes play with, can also lead to food poisoning. Even if they don’t eat it, the E. coli can get onto their hands, which usually end up in their mouth before they get washed.

In light of these cookie dough poisonings, manufacturers have started to use only pasteurized eggs and, more recently, heat-treated flour to destroy the bacterial culprits. However, they still caution that consumers cook the product properly to be on the safe side.

What about those of us who enjoy our desserts within a dessert, namely cookie dough ice cream? You can breathe easy - cookie dough ice cream is okay to eat because it is typically made with heat-treated flour and pasteurized eggs.

To put things in perspective, E. coli contaminated spinach sickened nearly 200 people and killed 3 of them in 2006. The point is not to eat more cookie dough instead of spinach (sorry)…but to handle and prepare ALL food properly no matter what it is.

Putting it all together, if you are making cookie dough or cake batter from scratch, odds are the flour you're using has not been heat-treated to kill bacteria, so there is a chance it could be contaminated. Even if it is not under the recall, the flour should be treated as you would any other raw food. If you must play cookie dough roulette, some companies are stepping up to the (kitchen) plate and making some that lacks eggs and uses heat-treated flour.

Contributed by:  Bill Sullivan

Follow Bill on Twitter.

Thorpe, C. (2004). Shiga Toxin--Producing Escherichia coli Infection Clinical Infectious Diseases, 38 (9), 1298-1303 DOI: 10.1086/383473

Obrig, T. (2010). Escherichia coli Shiga Toxin Mechanisms of Action in Renal Disease Toxins, 2 (12), 2769-2794 DOI: 10.3390/toxins2122769

Osteoporosis: The Dying Osteocyte

Bone is a highly dynamic tissue. Every year approximately 10% of an individual’s skeleton is resorbed and new bone is formed, which means that every 10 years your bones are made of entirely new material. We call this process “bone remodeling”. As we age, the balance between bone resorption and bone formation changes, leading to relatively more bone being removed and less bone being formed – this is called osteopenia, which refers to low bone mass, and is a normal consequence of aging. When the balance tilts excessively toward the loss of bone, we refer to it as osteoporosis.

Shuler F. ORTHOPEDICS. 2012    

Osteoporosis is a disease characterized by bone fragility and an increased incidence of broken bones, which results when an individual’s bones become thinner and more brittle.  Osteoporosis has long been thought to mainly affect elderly women; however, with the increasing use of prescription medicines such as glucocorticoids, and the large number of people leading unhealthy lifestyles, the incidence of osteoporosis is predicted to significantly increase in the future. In 2002, approximately 43 million people had either osteoporosis or osteopenia, and in 2020 this number is predicted to grow to nearly 61 million people.

Alterations in bone remodeling – the coupled action of bone resorption and bone formation – that lead to osteoporosis are a result of changes in the activities of the cells that carry out these processes. Bones are made up of three main types of cells:  osteoblasts, osteoclasts, and osteocytes. Osteoblasts are responsible for forming new bone, while osteoclasts eat away (resorb) the old or damaged bone. Osteocytes are osteoblasts that become entombed within the newly formed bone matrix, and they are the most abundant cell type accounting for nearly 90% of the cells. Osteocytes are the main regulators of the osteoblasts and osteoclasts. Osteocytes are among the main producers of the cytokine receptor activator of nuclear factor kappa-B ligand (RANKL) and the decoy cytokine receptor osteoprotegerin (OPG). The ratio of RANKL:OPG controls osteoclast formation because OPG is able to bind to RANKL and prevent its binding to the RANK receptor. On the osteoclast precursor surface, the cytokine RANKL binds to the RANK receptor and activates osteoclast differentiation and function of the osteoclasts, leading to increased bone resorption. The osteocytes embedded in the bone connect to each other through outgrowths called cannaliculi, creating networks within the bone that allow for the bone to sense mechanical stimuli and transmit signals between the cells.

www.medscape.com

Connexin (Cx) 43, a key protein involved in the formation of gap junctions, which are intercellular channels between the cells that allow for cell-to-cell communication. As an individual ages, the levels of Cx43 decrease and the number of dead osteocytes increases. Animal models with an osteocyte-specific deletion of Cx43 display increased osteocyte cell death, empty lacunae (the spaces in the bone cortex normally occupied by living osteocytes), and an increased number of osteoclasts along the bone surface. Experiments studying MLO-Y4 osteocytic cells lacking Cx43 also found an increase in cell death. Transfection of the Cx43 back into these osteocytic cells was sufficient to prevent this increase in cell death observed in this cell line. Osteocytes lacking Cx43 undergo a specific form of programmed cell death called apoptosis. The process of apoptosis is initiated through the action of multiple caspase proteins, including caspase-3. This increase in osteocyte apoptosis leads to the release of specific molecules and signals, which are involved in communicating with the osteoblasts and osteoclasts.

www.medicographia.com. 2012

To study the effects that osteocyte apoptosis has on osteoclast recruitment, we collected the conditioning media (the media containing growth factors that is added to cells) from Cx43-silenced and control MLO-Y4 cells that were either untreated or treated with DEVD, a caspase-3 inhibitor. This conditioning media was then used to treat non-adherent bone marrow cells that were treated with m-CSF (macrophage colony stimulating factor) and RANKL to induce osteoclast differentiation. This study found that blocking osteocyte apoptosis reduced the levels of soluble RANKL and prevented the increase in osteoclast recruitment and activity associated with osteocyte cell death.

The overall findings from this study suggest that Cx43 is required to maintain osteocyte viability and show that the increased osteoclast activity observed in Cx43 silenced osteocytes is a result of the increased osteocyte apoptosis. These findings provide a potential way in which osteocyte apoptosis could be targeted to prevent bone fragility in individuals with low bone mass.

Currently, the majority of osteoporosis drugs on the market work to maintain bone mass through inhibiting the activity of the bone resorbing osteoclasts. While these drugs are effective at preventing further bone loss, they do not reverse the bone loss that has already occurred before treatment has begun. This is because bone formation and resorption are coupled in bone remodeling*, so inhibition of resorption also decreases the amount of formation. The findings from this study provide evidence that specifically targeting osteocytes could allow for a therapeutic method to prevent bone loss and maintain bone mass through mechanisms that do not involve completely inhibiting the activity of osteoclasts.

* The uncoupled action of bone formation and bone resorption is referred to as “bone modeling”, which is one of the ways that bones can change their shape as we grow during childhood and adolescence.

Contributed by:  Hannah Davis

References:

http://www.medicographia.com/2011/05/osteoporosis-and-osteoarthritis-bone-is-the-common-battleground/

http://www.medicographia.com/2012/11/the-osteocyte-doing-the-hard-work-backstage/

Shuler, F., Conjeski, J., Kendall, D., & Salava, J. (2012). Understanding the Burden of Osteoporosis and Use of the World Health Organization FRAX Orthopedics, 35 (9), 798-805 DOI: 10.3928/01477447-20120822-12