Extensive Impact of Non-Antibiotic Drugs on Human Gut Bacteria
It is known that taking antibiotics can disrupt our gut bacteria (gastrointestinal microbiome) and result in unintended consequences for health and disease. Now, a new study reveals that many non-antibiotic drugs also alter the composition of our gut bacteria in a similar way. In a paper published in the journal Nature, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, report that not only can many common non-antibiotic drugs alter gut bacteria, but they can also - like antibiotics - contribute to antibiotic resistance.
In their study, the authors mention recent research showing that commonly used non-antibiotic drugs have been associated with changes in gut microbe composition; they also note that the extent of this phenomenon is unknown.
For their investigation, they compiled a panel of 40 species of bacteria that are typically found in the human gut and used it to screen more than 1,000 drugs currently on the market. Of the 923 non-antibiotic drugs that were analyzed, the researchers discovered that 250 had disrupted the growth of at least one of the 40 species of gut bacteria in the panel. They were surprised by the size of their result, especially as the drugs they tested included members of all therapeutic classes.
"This shift in the composition of our gut bacteria contributes to drug side effects," explains study author Peer Bork, who is a professor at EMBL and head of its Structural and Computational Biology Unit.
Abstract
A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.
Maier, Lisa, Mihaela Pruteanu, Michael Kuhn, Georg Zeller, Anja Telzerow, Exene Erin Anderson, Ana Rita Brochado et al. "Extensive impact of non-antibiotic drugs on human gut bacteria." Nature (2018).
Coffee Linked to Cancer - Acrylamide
North Americans love coffee. More than 3.4 billion pounds of coffee was consumed in the United States between October 2016 and September 2017, more than in the entirety of South America, according to the International Coffee Organization.
Recently, a judge has ruled that coffee sellers in California must warn people that coffee may contain a substance linked to cancer. Judge Elihu M. Berle, in Los Angeles County Superior Court, wrote in a proposed decision that the companies failed to show that acrylamide does not pose a significant risk when produced during roasting. Acrylamide has been identified as a possible cancer-causing substance. The chemical is naturally produced during cooking at high temperatures, including during the roasting of coffee beans.
The court ruling stems from a lawsuit filed in 2010 by the Council for Education and Research on Toxics, a nonprofit group based in Long Beach. The group charged that Starbucks and other companies - a group that eventually included 91 defendants - did not warn consumers that ingesting coffee would expose them to acrylamide. Judge Berle wrote, “Since defendants failed to prove that coffee confers any human health benefits, defendants have failed to satisfy their burden of proving that sound considerations of public health support an alternate risk level for acrylamide in coffee.”
California keeps a list of chemicals it considers to cause cancer or reproductive harm, and acrylamide has been included since 1990. The state’s Safe Drinking Water and Toxic Enforcement Act, known as Proposition 65 after it was passed in 1986, requires businesses to provide warning labels when exposing consumers to any of the hundreds of chemicals listed.
The Back Story - What is Acrylamide?
Acrylamide (ACR) is a chemical compound that is white, odorless and soluble in water. It is used in numerous factory processes such as the making of paper, dyes, and plastics. It is used to treat both drinking water and wastewater. Acrylamide has been detected in all kind of foods including meat, bread and potato products prepared at high temperatures (>160). Relatively small amounts can be found in boiled and microwaved foods, but not fresh ones. Acrylamide is also found in cigarette smoke and coffee. The National Cancer Institute notes that, among foods, coffee is a major source of acrylamide, along with potato chips, bread, breakfast cereals and canned black olives.
Acrylamide is formed in high-carbohydrate foods during frying, baking, roasting and grilling. In commercially processed foods, as well as in home-cooked meals, the acrylamide content tends to increase with cooking time and temperature. The surface color of the products correlates highly with acrylamide levels in food: the darker the surface, the more acrylamide it contains. This is the case even if healthy, high-heat fats like ghee or coconut oil are used.
The toxicity of ACR has been extensively investigated. In 2002, Swedish researchers discovered high levels of acrylamides in starchy foods. The foods highest in acrylamide after cooking or roasting include potatoes, grains, and coffee. What is most important to realize is that the longer and higher you cook starchy foods at temperatures above 250 F/121 C, the more acrylamide is produced. The FDA has reported Survey Data on Acrylamide in Food: Individual Food Products.
The main mechanism for acrylamide formation in coffee involves the amino acid asparagine. Through a cascade of reactions during the roasting of coffee beans, asparagine is converted into acrylamide in a process called the Maillard reaction responsible for color and flavor developments.
Acrylamide and Cancer
The World Health Organization (WHO) classifies acrylamide as a probable human carcinogen. This is based on data showing it can increase the risk of some types of cancer in lab animals. The WHO has not reviewed its position on acrylamide since 1997. At that time, acrylamide was not known to be found in so many starchy foods at such high levels.
The U.S. Food and Drug Administration has released a consumer warning on acrylamide to limit exposure. The warning is based on its high level of carcinogenicity in animals.
CDC scientists found measurable levels of acrylamide in the blood of 99.9% of the U.S. population. Smokers have nearly twice the levels of acrylamide in their blood as nonsmokers.
The US Environmental Protection Agency (EPA) maintains the Integrated Risk Information System (IRIS), an electronic database that contains information on human health effects from exposure to various substances in the environment. The EPA classifies acrylamide as “likely to be a carcinogen to humans” based on studies in lab animals. Allowable levels based on the toxicity data concurrently available had been developed by the U.S. EPA. New data have been published since the U.S. EPA review in 1991. Although the range of exposure (∼8 μg kg−1) is lower than other food items, coffee may account for a substantial proportion of total dose because of the frequency of consumption.
The major findings of these studies indicate that ACR is neurotoxic in animals and humans, and it has been shown to be a reproductive toxicant in animal models and a rodent carcinogen.
Tips for Avoiding or Reducing Acrylamide in Foods and Coffee
For potatoes, frying causes the highest acrylamide formation. Roasting potato pieces causes less acrylamide formation, followed by baking whole potatoes. Boiling potatoes does not produce acrylamide. If blanching the potatoes is not an option for you prior to cooking, you can also just soak raw potato slices in water for 15 to 30 minutes before frying or roasting. This preparation will reduce acrylamide formation when the potatoes are cooked. Be sure to drain and blot dry the soaked potatoes before cooking for safety reasons to prevent splattering or fires.
Beware! Potatoes should never be stored in the refrigerator. This can result in increased acrylamide during cooking. Potatoes are best stored in a dark, cool place such as a closet or a pantry to prevent sprouting. Sprouted potatoes contain solanine, a poison found in nightshade vegetables that can bring on gastrointestinal or neurological symptoms when ingested.
Avoid processed chips and snack crackers. North America’s favorite snack food - potato chips - contain the highest amount of acrylamides. However, many store-bought crackers and dried bread products (i.e., wheat thins, goldfish crackers, and rye crisp breads) also contain high levels of the chemical compound.
Acrylamides form when foods are overcooked, charred, or burned when left on the stove or grill for extended lengths of time. Steaming foods in moisture will prevent the formation of acrylamides. Acrylamide levels tend to increase when cooking occurs for longer periods and/or at higher temperatures. Take care to cook cut potato products, such as frozen French fries or potato slices, to a golden yellow color. Avoiding a medium to dark brown color helps reduce the formation of acrylamide considerably.
Toast bread to a light brown color rather than medium or dark brown. Very brown toasted areas contain the most acrylamide. Slough off any dark brown or burnt areas.
Acrylamide forms in coffee when the beans are roasted. Studies done both by the FDA as well as the European Commission have consistently shown that dark roasts are lower in acrylamide levels than beans that have been roasted in the regular manner. Light-roasted coffee, on the other hand, has the highest concentrations. This is apparently because acrylamide levels tend to rise at the beginning of the roast process but then decline steeply as the process continues.
Robusta beans have somewhat higher acrylamide levels than arabica beans. It seems that asparagine is a limiting factor for acrylamide formation in coffee, because Robusta coffees also contain higher amounts of asparagine than Arabicas.
If you are still concerned that coffee is a detriment to your health, two things you can do:
Reduce consumption of coffee;
Consider using coffee substitutes such as matcha, dandelion coffee, or yerba mate which is more popular than coffee in South America. Yerba mate provides a similar amount of caffeine without the acrylamide. Shilajit, though it does not contain caffeine, makes an excellent energy drink.
If you smoke tobacco, this is another reason to stop. People are exposed to substantially more acrylamide from tobacco smoke than from food.
The Benefits of Coffee
It is wise to view coffee’s effect on health from a wide and evidence-based perspective. Aside from the observation that coffee has been used "safely" for centuries, within the last decade, numerous studies have shown coffee’s beneficial effect on health.
A 2013 systematic review and meta-analysis of studies looking at long-term consumption of coffee and the risk of cardiovascular disease was published in Circulation. The researchers found 36 studies involving more than 1,270,000 participants. The combined data showed that those who consumed a moderate amount of coffee, about three to five cups a day, were at the lowest risk for problems. Those who consumed five or more cups a day had no higher risk than those who consumed none. Those authors concluded, “A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.”
Ding, M., Bhupathiraju, S. N., Satija, A., van Dam, R. M., & Hu, F. B. (2013). Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation, CIRCULATIONAHA-113.
In 2007, a meta-analysis published in Gastroenterology found that increasing coffee consumption by two cups a day was associated with a lower relative risk of liver cancer by more than 40 percent. Those authors concluded, “Findings from this meta-analysis suggest that an increased consumption of coffee may reduce the risk of liver cancer.”
Larsson, S. C., & Wolk, A. (2007). Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology, 132(5), 1740-1745.
Two more studies in 2013 confirmed these findings:
Sang, L. X., Chang, B., Li, X. H., & Jiang, M. (2013). Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis. BMC gastroenterology, 13(1), 34.
Bravi, F., Bosetti, C., Tavani, A., Gallus, S., & La Vecchia, C. (2013). Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clinical gastroenterology and hepatology, 11(11), 1413-1421.
In 2010, results from meta-analyses looking at prostate cancer found that in the higher-quality studies, coffee consumption was not associated with negative outcomes. Those authors concluded, “Given that a cohort study gives a higher level of evidence than a case‐control study, there is no evidence to support a harmful effect of coffee consumption on prostate cancer risk. Further prospective cohort studies are required.”
Park, C. H., Myung, S. K., Kim, T. Y., Seo, H. G., Jeon, Y. J., & Kim, Y. (2010). Coffee consumption and risk of prostate cancer: a meta‐analysis of epidemiological studies. BJU international, 106(6), 762-769.
A 2014 meta-analysis on neurological disorders found that coffee intake was associated with lower risks of Parkinson’s disease. Those authors concluded, “A linear dose‐relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings.”
Qi, H., & Li, S. (2014). Dose–response meta‐analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease. Geriatrics & gerontology international, 14(2), 430-439.
In a 2013 epidemiological study on cognitive decline, researchers found coffee, tea and caffeine consumption was associated with lower risk. Those authors concluded, “In general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.”
Arab, L., Khan, F., & Lam, H. (2013). Epidemiologic evidence of a relationship between tea, coffee, or caffeine consumption and cognitive decline. Advances in Nutrition, 4(1), 115-122.
A 2005 systematic review published in JAMA found that regular coffee consumption was associated with a significantly reduced risk of developing Type 2 diabetes, with the lowest relative risks (about a third reduction) seen in those who drank at least six or seven cups a day.
Van Dam, R. M., & Hu, F. B. (2005). Coffee consumption and risk of type 2 diabetes: a systematic review. Jama, 294(1), 97-104.
A follow-up 2014 meta-study used updated data and included 28 studies and more than 1.1 million participants. The authors concluded, “Coffee consumption was inversely associated with the risk of type 2 diabetes in a dose-response manner. Both caffeinated and decaffeinated coffee was associated with reduced diabetes risk.”
Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M., & Hu, F. B. (2014). Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes care, 37(2), 569-586.