Category Archives: You are what you eat
There is an interesting story that played on National Public Radio this morning, “Gut bacteria might guide the workings of our mind.” An audio link to the radio program can be found on their website. The story details work by Dr. Emeran Mayer, at the UCLA medical school. He has been working to correlate magnetic resonance imaging (MRI) scans with specific microbial fingerprints of gut flora from normal, random volunteers, and looking for areas of the brain that are associated with certain kinds of normal bacteria. The premise behind this is that the brain responds to hormonal and neurological cues from the gut, and the types of microorganisms in the gut play a direct role in the types of cues. Future directions for the research suggest that scientists might be able to modulate behavior by altering the types of gut bacteria (via probiotics) or by drugs that mimic the effects of the bacteria. One active area of research in this is towards correcting the effects of autism by altering the diet, an avenue that has already shown promise in mice. Other published research by Mayer has shown that sections of the brain associated with anxiety have been affected by probiotic diet. Findings such as these will continue to forcefully dispel the notion that our normal microbiota are not merely passengers on our bodies, but active participants influencing all aspects of our biology.
Click here to watch a video at NPR about this.
Long time readers of BIO230 know of my fascination with all things feces. One interesting idea is to use a fecal transplant from a healthy individual to someone with gastrointestinal disease as a potential treatment. There has been some excellent preliminary data that this is a useful approach, in particular for treatment of things like chronic Clostridium difficile infection. The premise is that an infusion of “normal” microorganisms will out compete and eliminate the pathogens in the digestive tract, resulting in recovery without the use of things like antibiotics. Indeed, the ability of C. difficile to form endospores makes that organism particularly resistant to antibiotic therapy, which is why some patients have problems clearing the infections even with long term antibiotic therapy.
The problems with fecal transplants have been several fold so far, and most have been related to collection and delivery. First, the organisms to be infused have to be to some degree tailored to the patient. It is better to acquire the normal microorganisms from a donor who would likely share a similar microbial makeup to the patient, and so a family member would be best. Quite frankly, I am pretty sure that I would not want a poop donation from a total stranger. Second, there is an “ick” factor associated with the process that requires either a feeding tube to bypass the stomach or else delivery via colonoscopy to put the donor organisms into the correct location. Passage of the donated material through the stomach would likely greatly reduce the viability of the microorganisms and diminish the effectiveness of the treatment.
A news update on Gizmodo reporting a CBSNews story details an innovation in fecal transplant technology, and summarizes research done by scientists at the University of Calgary. (Editorial note: I would take off points if I graded the CBSNews report, due to their egregious failure to underline or italicize the names of microorganisms!) The researchers treated 27 patients of persistent, antibiotic resistant C. difficile infections by administering donor microorganisms. The novelty of this approach was that the donor microorganisms (taken from a relative at home) were brought into the lab to be cleaned of food and other non-bacterial fecal material, and packaged into triple gel capsules before administering orally to the patients. The gel capsule allowed the donated microorganisms to get past the stomach, so that the capsules could dissolve in the intestines. One patient, a retired nurse’s aide who reported two years of debilitating gastrointestinal disease due to C. difficile, has been cured by the donor bacteria pills.
Currently, the treatments are essentially tailored by specific donors for each patient. Other gastroenterologists foresee the potential for “universal” donors who might be able to contribute organisms that might help many different, unrelated patients. Since the donated fecal material can be frozen and stored to produce “poop banks”. Alternatively, people might go for the Do It Yourself approach in order to avoid needing to deal with health insurance companies.
Via io9, a news alert about a huge multistate outbreak due to Salmonella. I’d be snarky in any summary I would put up, but is is unlikely that I would do as good of a job, so I will just refer everyone there. Please go read it! I would say that we can rest easy because the professionals are handling it, but that is not the case today. Wash your hands an extra time.
Update! Via CBSNews, apparently food monitoring workers at the CDC have been called back to work to deal with this. I only hope they will get paid.
Update 2! I have put up a placeholder post for the current flu season. As you might be able to tell, we don’t know how much flu there is, or where it is.
BIO230 correspondent Heather G sent me this link from the International Journal of Clinical Medicine, which details a fascinating case study of Gut Fermentation Syndrome. A 61 year old male presented with a long history of intoxication, however there were numerous times when it was clear that he had not been drinking. His blood alcohol levels were frequently noted to be 5 times over the legal limit. The episodes appeared to begin following treatment with antibiotics following surgery, and were more frequent after missing a meal or having a drink the night before. Exam by emergency room physicians in 2009 didn’t know of any way to become drunk without ingesting alcohol, and therefore assumed that he was a “closet” drinker. After referral to a gastroenterology practice in 2010, cultures of H. pylori were isolated from his stomach, and cultures of Saccharomyces cerevisiae and other yeasts were isolated from stool cultures. Following a controlled hospital stay where his blood alcohol levels were carefully monitored over the course of 24 hours following glucose challenge, it was concluded that the alcohol was being produced by his gut microorganisms.
Since this is a topic I could easily be passionate about, I decided to try and learn more. The article linked above had a brief review of the literature, and listed a few primary literature articles describing the phenomenon. My go-to citation finder at the National Library of Medicine was a bust, and turned up little of interest. A search of Google Scholar was perhaps a little bit more encouraging with the number of hits, however again most of the relevant items were not novel. Interestingly, most of the articles that I found dealing with alcohol and fermentation in the intestines dealt with the production of acetaldehyde from ethanol, which is in turn a potent carcinogen. In articles such as this one, the presence of alcohol in the upper digestive tract (presumably from long term alcohol consumption) acts as a substrate that can be further fermented by a variety of microorganisms into the terminal fermentation product acetaldehyde. This compound is strongly correlated with the development of tumors of the small intestine. The production of ethanol as a terminal fermentation product in the mammalian gastrointestinal system appears to be extremely uncommon.
All of the cases in the literature about the topic seem to have several things in common, and patients who develop the condition are typically on a unique diet which contains fermentable sugars, have a diminished bacterial gut flora due to antibiotic use, and have a unique mixture of yeasts which have in turn colonized their system. Fungi do make up an important part of the human gut flora, mainly Candida species, however I can find little evidence that Candida is able to produce ethanol as a terminal fermentation product. Most individuals who exhibit Gut Fermentation Syndrome appear to be colonized with a mixture of yeasts, including Saccharomyces cerevisiae. This is interesting in itself, as S. cerevisiae is a poor colonizer of the human body due to our body temperature, and few articles can be found describing this organism in a disease setting.
And so: an experiment for Science! We will need to start with the yeast. As I prefer a nice IPA, my searching indicates that something like yeast strain 1272 might be a good starter culture. We will need to get the organism adapted for growth in the human body, so we will have to do an enrichment culture at 37 degC, followed by assessment of alcohol production in vitro in the YCP Biology labs. Fortunately, we have in our possession a Vernier alcohol concentration probe, so this is trivial to accomplish. At this point, we will have two options in which to proceed. First, we could jump straight to human trials, however since most BIO230 students are under the age of 21, I think we will go with option two which is to conduct animal studies. We will use outbred CD-1 mice, and administer a broad spectrum oral antibiotic to reduce their normal gut flora, and repopulate with our new IPA yeast via the diet. Control animals will receive heat killed yeast in their diet. We also will administer one of two diets: either a normal rodent chow diet, or a diet which we have supplemented with fermentable sugars–this carbohydrate rich diet looks to be just what we would need. Mice which have been recolonized with our IPA yeast and fed the carb rich diet ought to exhibit behavioral traits that can be measured.
BONUS: For Bonus to be added to your course grade, suggest a method for assessing whether this works in vivo. Do not suggest having the mice recite the alphabet backwards, because unless you are these guys, it isn’t going to work.
Kristina Stefanik (12:00 Micro) found this article in Science Daily about the normal microbiota, human diet, and association with body mass index. Another summary of the research was recently up at Time.com. Here is Katrina’s report:
Just call me the next Dr. Oz (or Bill Nye); I’ve found the secret to becoming skinny! Unfortunately, it’s not in a food or a certain type of exercise…it’s in your breath. You saw it correctly…an indicator in your breath can reveal how likely or unlikely you are prone to weight gain. A study published in The Endocrine’s Society’s Journal of Clinical Endocrinology & Metabolism discovered that people whose breath contains increased concentrations of hydrogen and methane gases are more likely to have a higher body mass index and percentage of body fat. The presence of these two gases together strongly indicates the existence of a microorganism which supports obesity. It is better known as Methanobrevibacter smithii.
M. smithii takes up residence in the digestive tract- the prime site of absorption of nutrients. Earlier research confirms that this is the principal microorganism in the human gastrointestinal tract responsible for the majority of methane production. About 70% of people have these bacteria in their tract, while 30% have an elevated amount. Under normal circumstances, M. smithii in the digestive tract is viewed as beneficial. It helps us convert food into energy; however, the problem arises when the organism reaches excessive amounts. It operates as hunter for hydrogen emitted from other microbes and uses that hydrogen to produce the methane exhaled in our breath. The other microbes seemingly benefit from this relationship; they flourish and extract nutrients from food more effectively. Therefore, the higher amount of M. smithii, the more efficient the hydrogen-producing bacteria become. Over a long period of time, this uptake of excess nutrients contributes to weight gain. As stated in the article, this essentially allows a person to harvest more calories from their food.
The study analyzed the breath of 792 people. From this, four patterns appeared. The test subjects had normal breath content, increased content of hydrogen, higher concentrations of methane, or higher degrees of both gases. Accordingly, as the article states, the subjects who possessed higher concentrations of both gases had significantly higher body mass indexes and higher percentages of body fat. More specifically, their BMIs were about 2.4 points greater than those with normal levels of the gases and had about six percent more body fat on average.
Ruchi Mathur, MD, director of the Diabetes Outpatient Treatment and Education center, is continuing a study funded by the American Diabetes Association. As the Time article states, she is working with a group of overweight and obese pre-diabetics that tested positive for methane on their breath. Mathur and other researches will begin to test the participants’ glucose tolerance, measure how long it takes for food to travel through their intestinal tract, and take their stool to the lab to determine the amount of calories in it. After this has been established, the participants will then receive an antibiotic to kill the colonies of M. smithii. They will undergo the same procedure and will essentially be able to determine if eliminating the microbes will alter the person’s weight conditions and overall health. It is amazing to think about how something so small could have such a major impact on something like weight gain!
Katrina Stefanik (12:00 Micro) found this news article via Science Daily describing how a bacterium can cause disease in the human stomach, and probably NOT a disease you were thinking of. Some of her background information came from the National Cancer Institute’s website as well. Here is an article I found about Helicobacter pylori that tells a little bit different story; it seems that H. pylori in the human gut can act to suppress the appetite, which suggests that reduction of the numbers of this bacteria might be linked to increases in childhood obesity. Remember folks–in medicine we like to have nice, neat little connections between things, however in reality the interactions between things are FAR more complicated that you might imagine. Here is Katrina’s report:
Microbiology is making me wary of all these little microbes running around and infecting everything and everybody with their diseases! Now I know, Dr. Singleton, that you mentioned not all microbes are negative, as our textbook unfortunately portrays…but I’m not really getting a welcoming feeling from these little guys! Something that caught my attention as I was browsing the internet talked about wonderful stomach bacteria which compromise the human immune system to trigger disease. It is better known as Helicobacter pylori and creates life-long stomach infections such as duodenal ulcers or stomach cancer.
The human stomach is a very acidic place in the body, but H. pylori are clever bacteria. In order to survive the adverse conditions of the stomach, H. pylori emit an enzyme better known as urease. Urease converts the chemical urea to ammonia; this neutralizes the acidity of the stomach. The bacterium is then able to survive in this environment. H. pylori also demonstrates a helical shape (Helico=helical!), which allows it to bury into a less acidic mucus layer of the stomach. Our immune cells do recognize this foreigner, but since it is in the stomach, they are unable to reach it.
Healthy bodies produce an antimicrobial component in the stomach lining called ‘human beta defensin 1’; these guys assist in preventing bacterial infection. When 54 stomach tissue biopsies were taken from at the Queens Medicle Centre in Nottingham, it was found that diseased patients with H. pylori had TEN times less ‘human beta defensin 1’ than healthy patients! The patients with the highest amount of bacteria in their stomach lining also demonstrated a low amount of the ‘human beta defensin 1.’ So what does this mean? It is obvious that H. pylori must repress the making of our bacteria-fighting soldiers.
In a unique process, H. pylori creates cagT4SS; this is a molecular ‘syringe’ in which bacterial products are instilled into the stomach lining cells. After this injection, chemical pathways are activated to decrease ‘human beta defensin 1’ creation. Oh- it gets better. As if that wasn’t good enough for the bacteria, they found that the same activated pathways are involved in the stimulation of an inflammatory response. What this entails is that while bacterial strains are flourishing under favorable conditions and diseasing us, they are also causing us tissue damage.
According to the article, more than half the of world’s population contain H. pylori. It is quite troubling to think that probably someone in my immediate or extended family has this bacteria hanging around in the mucosal lining of their stomach. Heck- it might even be me! Fortunately, for most people, the infection is asymptomatic. This means that there are carriers of the disease, but these people are not experiencing the symptoms or implications. Phew! However, 1-2 percent of the infected will develop gastric cancer. When gastric cancer becomes apparent to the patient, it is often too late and the cancer is too far developed. Because of this, survival rates are seemingly very low.
I definitely enjoyed reading about this and talking about it. As a future nurse, this makes me much more appreciative of these microscopic organisms and their enormous effect on patients.