Category Archives: You are what you eat
Brittany Reichelt (11 AM Micro) is thinking outside the box with the treatment of Clostridium difficile infections. These infections are difficult to treat, in large part due to the fact that they can form endospores, and as a result are not easily eliminated by antibiotic treatment. This leads to many patients have long term gastrointestinal issues from the infection, and a generally unsatisfactory quality of life for the patients with these infections. Brittany found this summary via the National Institutes of Health news page (excellent choice!). FYI, the use of poop to treat C. difficile infections is not news to long time BIO230 fans–it is a topic near and dear to my heart (see here, here, or just search “poop” on the blog). Here is Brittany’s take and summary on this important topic:
The following summary is on an article from the National Institutes of Health on Clostridium difficile. We have heard about the genus Clostridium with infections, such as Clostridium botulinum and Clostridium tetani. Clostridium difficile has many of the same characteristics, such as endospore forming and is anaerobic. This bacterium C. difficile is most prevalent in people with prolonged use of antibiotics, since antibiotics kill the bad and good bacteria in the colon, it will be easier for C. difficile to make its home there. Normally for treatment, antibiotics are not effective in improving the symptoms. Instead, the recommended treatment is to transplant “microbe-rich stool samples from healthy people into the C. difficile patient to help improve the bacteria in their colon and improve their symptoms.”
In the study completed by National Institutes of Health funded researchers from Massachusetts General Hospital took a different approach. Rather than taking the poop of healthy individuals and transplanting it into the patients, they created a simple pill: “the poop pill, which is shown in the picture above.” Researchers completed this by first taking healthy poop samples, purifying them, and then concentrating the good bacteria it. The concentrated good bacteria was put into clear capsules and then froze, these poop pills were to be given to patients frozen. Researchers tested the effects of the poop pills on 20 patients who experienced “at least three C. difficile infections and did not respond to antibiotics normally used on this bacterium. Patients were given 30 pills over a period of two days. The results of this study showed in 2 days of treatment 14 out of 20 patients had a dramatic reduction in symptoms, such as frequent diarrhea went away. The resulting 8 patients were given a second round of treatment and 4 more patients had the same decrease in symptoms.
The results show that this may be a better alternative; it is much easier for a patient to take a pill then it is to transplant the poop from one human being to another human. Researchers say that someday, this treatment may even be beneficial for other gastrointestinal diseases.
(note added in proof by Singleton: this seems as good as an opportunity to bring out this old chestnut–any ideas why this graphic is completely relevant to Brittany’s story? First person to comment with the correct answer gets a free bonus point!)
Rebecca Donovan (11 AM Micro) is interested in the normal microbiota. I have had a long-standing interest in the role of the gut microbes, and how recent studies have implicated them in a variety of phenomena–see for instance this report about how gut bacteria play a role in mate selection, or this one about a dating service based on gut bacteria. Rebecca’s summary shows that what we feed those bacteria is as important as the types of microbes themselves. Here’s Rebecca’s story, and for those who read to the end, a BONUS opportunity:
A recent article, published on sciencedaily.com, discovered that artificial sweeteners may be doing more harm than good in your body. Originally marketed to be the ideal solution to those desiring a lower calorie, “sugar less” way to avoid diabetes, recent research has suggested that artificial sweeteners are actually promoting glucose intolerance in the body. If, by this point, I have not convinced you to put down that diet coke in your hand, please read on.
How does this happen?
According to Dr. Eran Elinav and Professor Eran Segal, both of the Weizmann Institute of Science, our gut microbiota, or the bacteria residing in our intestines, are the likely culprits. To confirm this idea, the scientists gave mice water that contained three of the most readily used artificial sweeteners, saccharin, sucralose (splenda), and aspartame (Equal). They found that giving these mice the artificial sugar water promoted development of glucose intolerance to a much greater extent compared to mice only given plain water (Weizmann Institute of Science, 2014). It is also worth noting that mice who were given water containing real sugar developed less of an intolerance to glucose compared to mice given artificial sweetener water. Next, the scientists “cleaned out” the microbiota in the mice through the use of antibiotics. This “clean sweep” of gut bacteria resulted in a return of tolerance to glucose in mice given artificial sweetener water, solidifying the claim of the researchers that gut bacteria are the “prime suspects” in glucose intolerance brought on by artificial sweeteners.
How do these findings pertain to humans? (After all, we’re not mice!!!)
The scientists involved in this experiment “covered their bases” by gathering a group of human volunteers, who rarely consumed artificially sweetened products, to add them to their diets for a week. After this time, their blood glucose levels would be measured. Their gut microbiota would also be analyzed and measured. The results of this experiment were that most of the participants exhibited an intolerance to glucose after ONLY ONE WEEK of consuming artificial sweeteners. Further analysis of the gut bacteria of participants illustrated that, with consideration to those whose intolerance levels towards glucose were not adversely affected, that there are two types of gut bacteria living within humans: a type that reacts negatively to glucose resulting in intolerance and a type that has no effect on glucose tolerance (Weizmann Institute of Science, 2014). The researchers involved in the experiment believe that the aforementioned “bad” gut bacteria “turned on” an inflammatory process in the body, negatively affecting the ability of the body to effectively process sugar.
What should this study teach us?
The ultimate question we should ask ourselves is: why would we want to put substances in our body that are proven to be harmful to us? Diabetes and obesity are still, and will continue to be on the rise, in America if we continue to do little to prevent these diseases from occurring. You can take the first step in preventing diabetes and obesity by eliminating “diet” from your diet. Artificial sweeteners aren’t worth the risks associated with them.
BONUS added by Singleton: in the comment thread, give an example of an association that the normal microbiota has with ANY aspect of human health (good or bad). No repeats, so read what others have put in, and you must give a citation (URL). Don’t worry about formatting of names–I will fix–but do spell them correctly. Offer ends on the end of the day on Friday September 26th.
A news article that made the rounds through the popular press this week caught my eye: “Commensal bacteria protect against food allergen sensitization,” which appears in the early access section of the journal of the National Academy of Sciences. I have been a big fan of this type of research for a while now. The basic premise is this: our modern lifestyle has potentially begun to diminish the numbers and variety of microorganisms that live on our bodies in the absence of disease (the normal microbiota), and as a consequence, benefits that these benign organisms can confer to us are being lost. So far, loss of diversity of the normal microbiota have been correlated with a long list of ailments including potentially autism and cancer.
An opinion piece in this week’s Nature warns against drawing too many conclusions from these studies, and suggests that over reporting of some of them by the press reinforces the need to ensure that the public understand the distinction between “correlation” and “causation”–these concepts are frequently confused, and the distinction is sometimes not clear. Indeed, the editorial in Nature suggests that reporting of microbiome analysis and human disease should be tempered by asking 5 questions:
- Can experiments detect differences that matter? Characterization of microbiomes is generally accomplished by sequencing very highly related genes, and this analysis may hide real differences.
- Does the study show causation or just correlation? Many of the cases of a disease association with certain microorganisms may be the result of conditions in the body becoming favorable for the microbe, meaning the disease caused the microbes to alter.
- What is the mechanism? Demonstrating causation is important, however without an explanation of how a change occurs, it is not sufficient.
- How much do experiments reflect reality? Many of the putative effects of the microbiome on health involve germ free mice; that is mice that have been raised to have no normal microorganisms of their own, as this makes interpreting the effects somewhat easier. However, mice and humans are not the same, and the microorganisms that live on each are not the same.
- Could anything else explain the results? Many things can cause disease, and other factors should be considered and tested.
With this in mind, I read the article on food allergies linked up at the top. The authors carried out the study to address the hypothesis that the normal microbiota of the gastrointestinal tract are able to guide adaptive immunity at this site. The intestinal tract of animals hosts an incredible variety of organisms in the absence of disease. The immune system needs to be non-responsive to these organisms, as well as to all of the food antigens that enter the digestive tract. Immune cells in lymphoid tissue along the digestive tract modulate signals between the microbiota and the epithelial barrier of the digestive tract, which helps to prevent an ongoing inflammatory response, and thereby promote a homeostatic relationship between the microbiota and the host.
The researchers first experiment was to treat neonatal wild-type mice with an antibiotic regimen prior to weaning to eliminate intestinal microbiota, then sensitized by gastric administration of Peanut Antigen (PN). Three weeks later, the mice were challenged with the antigen and allergic responses were measured a day later by collecting blood. Control mice had essentially undetectable levels of allergic responses, while antibiotic treated mice showed highly elevated levels of IgE. Analysis of the bacteria from feces of mice at the same time intervals also showed that the antibiotic treated mice had lowered levels of fecal bacteria, and greatly diminished diversity of fecal bacteria. Specifically, members of the prokayotic phyla Bacteriodetes and Firmicutes, present under normal conditions, were essentially absent in the antibiotic treated mice. These bacteria were replaced with members of Lactobacilli, a result consistent with another recent report examining changes in the microbiota of antibiotic fed mice. The results outlined above were achieved using outbred mice strains housed in pathogen-free, but not germ free conditions; therefore this study addresses one of the critiques above with the use of outbred mice.
This paper was also significant, in that the authors also propose a mechanism for how the immune modulation occurs. Recolonization of antibiotic fed mice with a group of Firmucutes from genus Clostridium (the major genus of the Firmucutes from normal mice), prevented the allergic response produced by peanuts. Dissection of the intestines from these animals indicated that specific T cells involved in adaptive immune regulation are more prevalent in Clostridia colonized mice. Additionally, mice colonized with Clostridia in comparison to germ free mice and control mice exhibited high levels of an immune cytokine Interleukin 22 (IL-22). The authors propose that IL-22 (induced by the presence of Clostridia) causes the intestinal epithelial barrier to be reinforced, reducing the permeability to dietary proteins. To address this possibility, they then measured the levels of food allergens in the bloodstream after intragastric gavage. Colonization by Clostridia resulted in significantly lower levels of these allergens in comparison to germ free mice, supporting this hypothesis.
The major conclusions of this paper support the important role of the benign normal microbiota in promoting health. Their model argues that tolerance to food antigens is aided by the presence of those antigens along with specific components of the normal microbiota. To translate this work to human therapies, the role of Clostridia needs to be confirmed in humans. Indeed, other work has shown that Clostridia species isolated from human feces do induce the same immune regulatory cells discussed above when transferred to germ free mice, suggesting that they may be playing similar roles in both species.
Via the ever helpful Morbidity Mortality Weekly Report, another alert about the dangers of foodborne-illness! The Minnesota Department of Health reported in late July 2013 two cases of invasive listeriosis, for which molecular analysis indicated a sole-source for infection. As an aside, the Minnesota Department of Health seems to be the hardest working state department of health, as evidenced by this alert about Salmonella from Guinea pigs, and this alert about Salmonella from phlebotomy that I found in the BIO230 archives. Way to go, Minnesota Department of Health!
Once the Centers for Disease Control and Prevention were notified, further analysis indicated that the isolate was also identical to an environmental isolate collected from a cheese producer in 2011. With this in place, several other cases were also identified by the CDC in last summer’s outbreak, resulting in one death and one miscarriage. All patients were interviewed to determine their “cheese exposure.” All patients indicated that they had likely eaten one or more of Crave Brothers Farmstead Cheese varieties (Les Frères, Petit Frère, or Petit Frère with truffles) during the likely time frame for infection, at either grocery stores or restaurants in the region. All of the cheeses were shipped as intact wheels to the point of sale, where they were cut and repackaged.
The manufacturer issued a voluntary recall when news of the outbreak was made public. Conjecture by the CDC suggested that the contamination arose during the manufacturing process. The process of pasteurization very effectively eliminates Listeria monocytogenes from milk, however in the cheesemaking process contamination can occur after the original pasteurization. The CDC recommends that strict sanitation and monitoring of contamination steps always be in place for cheesemakers, regardless of whether pasteurized milk is used.
The CDC also reiterated standard precautions to protect against infection by Listeria, which again bear repeating. The organism does not generally pose a significant health risk to the general population, however immunocompromised individuals can become quite seriously ill. Additionally, pregnant women can pass the organism onto the developing baby, and fetal infection due to Listeria is a significant cause of miscarriage. Because of these risks, at risk individuals are strongly advised to avoid any food that carries the potential for infection by Listeria.
It’s been a while since I have reviewed the various risks associated with eating, but I came across this Salmonella menace a few weeks ago. The Centers for Disease Control and Prevention published a case study describing a multistate outbreak of Salmonella enterica serotype Chester due to frozen meals. In November the CDC reported that 44 people became ill in 18 states during the late spring of 2010. Molecular analysis of patient isolates indicated sole source contamination and questionnaires completed by the patients suggested that “brand A cheesy chicken and rice frozen meals” were responsible. Of the 43 patients who were followed up, 16 of them required hospitalization however no deaths were reported. On the strength of the epidemiological analysis, the company recalled the product from the shelves and the outbreak strain was identified in 8 unopened containers. Investigation into the source during the manufacturing process did not turn up any production deficiencies or a conclusive common contaminated ingredient supplier. The best guess was that a single poultry supplier was the source in the outbreak. What made this case novel was that this episode represents the first time that Salmonella enterica serotype Chester had been reported in a widespread foodborne disease outbreak.
Editorial notes by the CDC point out that there is little in the way of negligence in either the supplier or production procedures used to bring this product to market. Simple Google image searching showed that the dinner in the above graphic was the one recalled in this outbreak. The label clearly says “Keep Frozen–Must be cooked thoroughly” and is considered a “not ready to eat” meal, as opposed to the hugely convenient “heat and serve” meal. Organisms such as Salmonella enterica and Shiga toxin-producing Escherichia coli are not effectively killed by incompletely reheating in the microwave, and require actual cooking in order to render them inert. The instruction to “allow dinner to sit in the microwave for 1 minute” is also a critical part of the cooking process, and is frequently ignored by consumers. The CDC notes that this outbreak highlights the need to educate the public on safe food handling procedures, and the need to follow the instructions prior to eating these products. Consumers also, if using a microwave oven to cook these products, need to know the specifications of their appliances and to ensure that their microwave ovens are able to be safely used to cook these.
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.