What can you learn from your poo?

I delivered the bad news to my husband on Christmas morning, “Oh no! You have the bad gut microbes!”  Back in June, we sent stool samples to the American Gut project, and we happened to receive our results just in time for the holidays.  My proclamation stemmed from my knowledge of several high profile scientific papers, which found that a higher ratio of a specific group of bacteria correlates with obesity (1-3).  Kevin’s gut is dominated by these same bacteria.  Upon further reading, however, I discovered another more comprehensive study of lean and obese people that found no signature pattern of gut microbes (4).  I realized that although it is incredibly interesting to learn which microbes live inside of us, this science is still too young to jump to any definitive conclusions.  Determining which bacteria inhabit our bodies is the first step in understanding how these organisms influence our health, and  participating in studies such as American Gut will help to collect information such that in the future we may be able to make health recommendations based on our microbial populations.

        Gut microbes?  By now you may have heard that bacteria living on your body outnumber your own cells 10 to 1.  These bacteria both eat and excrete as part of their daily routine, so it is not difficult to imagine that these single-celled organisms affect our bodies’ physiology.  Currently, the microbes on our skin, in our mouths, genitalia, and guts are being characterized in hopes to better understand how they influence our health (for example, the Human Microbiome Project).  Most of these scientific studies focus on identifying which bacteria live on us.  With this information in hand, researchers can further analyze these microbes to determine their metabolic potential.  After cataloging who lives on us, the next questions involve categorizing what these bacteria are capable of metabolizing -- what molecules are they releasing, and how do these compounds affect our health?  But logically, we must first begin to understand “who” before we can most effectively answer “what” they are doing.

          In my quest to figure out who lives on me, I joined the American Gut project.  This study is interested in determining how your diet influences your microbial population.  Therefore before you send in your sample, you are instructed to keep a food journal for at least a week, which details everything you consume.  On the day you ship your sample, you fill out a detailed questionnaire including your daily percentage of calories from carbohydrates, protein, and fat as well as how many different species of plants you eat in any given week.  Several months later, you receive a poster in the mail that summarizes your results. 

    Here are some of the highlights of my gut microbes:

Humans are colonized by four main groups of bacteria - predominately Bacteriodetes and Firmicutes, with smaller populations of Actinobacteria and Proteobacteria.  These groups are referred to as phyla. If you remember from biology, all living organisms can be organized according to how closely they are related.  As you move down the scale of kingdom, phylum, class, order, family, genus, and species, the more genetically similar two living beings are.  For example, plants and animals are in different kingdoms, whereas humans share the same family with chimps, gorillas, and orangutans.  The plot above shows that my gut microbiota is dominated by the phylum Bacteriodetes.  In contrast, my husband contains mostly Firmicutes, which was surprising to me because we live together and eat basically the same food.  I also convinced my grandmother to participate in the study.  Interestingly, her gut is colonized with predominately Bacteriodetes, like me, which suggests that genetics may play a role in shaping our gut ecology.

        My most abundant microbe (71.5%!) is a subgroup of Bacteriodetes, the genus Bacteriodes.   This result is consistent with the finding by Wu et al. that consumption of saturated fat and animal protein increases these microbes (5).  I do not eat mammals, but I do consume plenty of dairy products, which are full of these nutrients.  This same study also showed that the genus Prevotella (phylum Bacteriodetes) is associated with diets rich in plant material and fiber, which unfortunately were not present in my stool despite the fact that I eat a lot of vegetables.  Bacteriodes, however, can also break down plant starches.  This example shows that although it is helpful to know which microbes live on me, it would be even more useful to know what metabolic functions my microbes possess and furthermore what my Bacteriodes are actually eating and excreting inside of my gut.

       Switching gears to some of my bacteria in different groups, my gut contains Faecalibacterium (phylum Firmicutes), whose presence is inversely correlated with gut inflammation, which is good (6). I also have an enriched population of Sutterella, which belong to the order Burkholderiales (phlyum Proteobacteria).  These bacteria may be enhanced on a diet that is high in cruciferous vegetables (broccoli, cauliflower, cabbage, etc) (7), which I do eat a lot of.  If specific vegetables enrich bacterial populations in our guts,  how stable is our gut ecology?  Does it change after every meal?  Or only after a dramatic shift in dietary habits?

        Diet influences our bacterial populations because what we put in our mouth ultimately selects for the type of bacteria that will thrive in our guts.  Nutrients that are not absorbed by our bodies provide fuel for our gut microbes.  Can we change our microbial landscape by changing our diet?  I’ll go into more detail on this topic next time, so stay tuned.

References:

1.  Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, et al. Obesity alters gut microbial ecology. 2005. Proceedings of the National Academy of Sciences, 102: 11070–11075.

2.  Ley RE, Turnbaugh PJ, Klein S, Gordon JI, et al. Microbial ecology: human gut microbes associated with obesity. 2006. Nature 444: 1022–1023.

3.  Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, et al. A core gut microbiome in obese and lean twins. 2009. Nature 457: 480–484.

4.  Finucane MM, Sharpton TJ, Laurent TJ, Pollard KS. A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter. 2014 PLoS One 9:e84689

5.  Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. 2011

Science 334: 105–108

6. Willing, B. P. et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. 2010. Gastroenterology 139: 1844–1854

7.  Li, Fei; Hullar, Meredith A. J.; Schwarz, Yvonne; Lampe, Johanna W. Human Gut Bacterial Communities Are Altered by Addition of Cruciferous Vegetables to a Controlled Fruit- and Vegetable-Free Diet. 2009. Journal of Nutrition 139: 1685-1691

Did you get your 10,000 steps today?

For Christmas this year, my mom bought my whole family the Fitbit Force.  For those of you who are unfamiliar, the Fitbit tracks your daily “steps, distance, calories burned, stairs, active minutes,” and even sleep!  The hope is that wearing this device will motivate people to be more active by quantifying their daily movements.  So far, it seems to work and has even inspired some late night dance parties to help reach the daily 10,000 step goal.  This device is just one example of how technology is advancing our health awareness.

The “quantified self movement,” “life logging,” and “personalized medicine” are pretty common buzzwords these days.  Smartphone apps and miniature computer devices like the Fitbit allow people to track, in detail, many aspects of their lives.  Counting steps or calories are examples of how you can quantify your life.  The act of keeping track of these numbers on a daily basis is known as life logging.  Personalized medicine is a bit more tricky to describe.  I recently stumbled across an ethics paper that sought to definitively define personalized medicine:  “Personalized medicine seeks to improve stratification and timing of health care by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics.”  In other words, by sequencing your genome, or identifying and quantifying all of the compounds in your blood (e.g.) you can more accurately diagnose and treat health issues.

To illustrate how keeping track of your daily habits can benefit your health, I turn to the work of Dr. Larry Smarr.  My mom recently saw him speak at the Atlantic Meets the Pacific.  You can watch his 2012 lecture here or read an article about him in the Atlantic.  In addition to physical activity, Dr. Smarr monitors his heart rate and sleep, gets his blood tested regularly, has had his genome sequenced, and also sequences his gut microbes.  With this information, he was not only able to lose weight, but he also discovered that he had an inflammatory bowel disease before he showed physical symptoms.  The idea is that the more we know about our bodies’ biochemistry, the more quickly we will be able to identify potential illnesses and therefore seek treatment faster.  Who knows, some day there may even be toilets that give you a read out of your gut microbial population every time you flush!

You may think that obtaining your genetic information, for example identifying your gut microbes, is a far-fetched idea.  However, there are services available to the public that either sequence your microbes’ or your own genome.  I recently participated in the American Gut Project, which for $99 you can have your body part of choice sequenced (skin, gut, mouth, etc).  This study aims to collect data on how diet and lifestyle affect our microbial friends.  uBiome is a start-up seeking to inform the public of their microbiomes ($89/kit).  If you’re only curious about your own genome, you should look into 23andme.  However, the FDA has currently banned the company from making health recommendations based on individual’s genetic data, but they may change their policies in the future.

Current medicinal practices focus on treating illnesses after they become symptomatic.  But what if you could prevent the problem from happening in the first place?  By quantifying your daily habits, you become in tune with your body and its needs.  This information is invaluable for goals such as losing weight, but it also equips you with more knowledge to share with a healthcare professional should an illness arise.  Everyone has unique health requirements, and therefore it is time for everyone to start paying attention.

Citations:

 

Schleidgen S. et al. 2013. What is personalized medicine: sharpening a vague term based on a systematic literature review.  BMC Med Ethics 14: 55

Why you should support open access science

When writing the last blog post, I included references for further reading.  If anyone who was not affiliated with a university tried to read these papers, you would find that you would have to fork over $30 or so per paper to view anything besides the abstract.  Considering that reading one of these articles may stir your interest in further research, you could quickly find yourself on a very expensive paper journey.  It was from the frustration with this ensconced system that the open access movement was born.

Before I describe what open access means, I thought I’d give a brief description of the publishing process.  The life of a scientific paper begins as a manuscript, written by scientists to communicate their latest results.  Once the manuscript is complete, it is submitted to a journal of the author’s choosing.  The staff of the journal first assesses whether the manuscript fits their organization’s specific scope.  If so, they send the manuscript to two to three reviewers, who are experts in a specific field, for example professors at a research university.  The reviewers determine whether the science is sound and give their opinion whether they think the manuscript should be published.  They send this information back to the journal editor, who then makes the final decision as to the fate of the manuscript. Historically, subscription and advertising fees supported most peer-reviewed journals.

With the popularization of the Internet, publishing scientific articles online became easy and inexpensive.  This technology facilitated the creation of the open access movement.  The main tenet of open access, as outlined in the 2002 Budapest Open Access Initiative is that literature “should be freely accessible online.”  Publishing articles on the internet not only increases the speed at which information can be shared, but it can also be done at a much higher volume as compared to print.

Access to scientific research at no cost benefits society in a number of ways.  For instance, it assists small businesses in cost savings when developing new techniques.  Subscription fees for non-open access journals are quite expensive, often prohibiting readership from those with less capital such as universities in developing countries.  Therefore open access journals bolster research programs at these institutions.  Finally, free scientific articles allow healthcare professionals (e.g. physicians, physician assistants and nurses) to keep up with the latest research, which helps them to make more informed decisions when treating their patients.

Recently Dr. John Bohannon, a reporter at Science, exposed a downfall of the rapidly growing open access publishing industry.  He concocted a manuscript describing a fake anticancer drug candidate.  He purposefully included flawed experiments that “any reviewer with more than a high-school knowledge of chemistry and the ability to understand a basic data plot should have spotted.”  He submitted different versions of this faux article to 304 open access journals.  Surprisingly, more than half of them accepted the manuscript, many of which without any apparent peer review.  This sting reveals the predatory nature of some of the budding open access journals and also the lack of quality peer review.  Hopefully Dr.Bohannon’s exposé will motivate open access publishers to address their weaknesses.  

So how do open access journals pay their editorial and IT staff?  Instead of charging for subscriptions, the journals instead charge the authors to publish the articles.  In countries with well-funded research programs, this fee is usually not a concern.  In developing nations, however, the publishing fee could be a major hurdle.  Therefore many open access journals offer discounts or fee waivers to those under financial hardships.

You can support open access through Amazon’s Smiles program.  For every eligible purchase you make Amazon will donate 0.5% to the Public Library of Science (PLOS), a nonprofit publisher, to help support authors who cannot afford their publication fees.  (NOTE:  PLOS ONE rejected the faux Science manuscript due to its poor scientific quality.  Also note the impeccable timing of this post, which may or may not be a blatant plug for PLOS!)  This donation costs you no money, so no excuse not to sign up! 

What happens when you eat too much protein?

 

           

            An exercise recovery shakes salesman recently posted up outside of our gym, offering free samples to interested members.  Although I do not particularly subscribe to post-workout reconstituted beverages, he piqued my interest.  When I told him that I would like to try the “protein” formulation, he responded, “That has too much protein in it for you.  I’m only going to give you 2/3 a scoop.”  While he measured out my soon-to-be drink, he recommended the “women’s” formulation instead.  I was somewhat taken aback, but his proclaim got me thinking, what does happen when you consume too much protein?  Is my effort to build more muscle instead detrimental to my health?

            Proteins play many roles in biology.  They facilitate biochemical reactions (enzymes).  They serve structural and mechanical functions such as forming scaffolding for cellular structure and executing muscle contraction.  In addition, they often act as signaling molecules that relay messages between cells.  Proteins are synthesized in the cell by linking together building blocks known as amino acids.  There are 20 standard amino acids that represent a variety of different chemical functionalities – acidic, basic, aromatic, polar, and hydrophobic – that can be combined to form proteins with diverse structures and functions.  Humans can create all but 9 of these amino acids themselves, and therefore rely upon their diet to supplement these essential protein building blocks.

            The National Academy of Sciences Institute of Medicine Food and Nutrition Board recommends that both men and women consume “0.8g of good quality protein/kg body weight/d.”  For a 67kg person, like myself, this amounts to roughly 54g of protein/day.  In other words, I should eat 1 cup of cottage cheese and a 3.5 ounce piece of chicken breast (about half of a large chicken breast) per day.  Prior to joining the aerobic/weightlifting/gymnastics cult known as CrossFit, I definitely did not make it a priority to consume protein.  Now I try to consume protein at every meal, which puts me over my daily-recommended intake.  

            After eating your favorite meat/cheese/protein source, the food makes its way from your mouth down to your stomach.  Its acidic environment, combined with enzymes secreted by the cells lining the stomach, break down the proteins into individual amino acids.  As the food travels from the stomach, to the small intestine, and then to the large intestine, different proteases (enzymes that break down proteins) are released to further digest the proteins.  These free amino acids are then absorbed by the epithelial cells lining the respective organ and taken up into the blood stream, through which they make their way to the liver.  Here, transaminases and deaminases (enzymes that transfer and remove amino groups respectively) break down the amino acids into alpha-keto acids and ammonia.  The alpha-keto acids can be utilized for energy production, whereas the ammonia provides a nitrogen source for the biosynthesis of new proteins, nucleotides (DNA and RNA building blocks) or other biological amines.  If there is excess ammonia, it is excreted, for example as urea in urine.  Consumption of protein most importantly provides a nitrogen source for a variety of biomolecules.  When other more easily metabolized sources of energy are low (e.g. carbohydrates or fats), proteins can be used instead.

            But what if not all of the free amino acids are absorbed into the bloodstream?  What if some slip through and are instead exposed to the trillions of bacteria that inhabit our guts?  Our commensal bacterial friends feed on the nutrients that are not readily absorbed by our gastrointestinal tract and generate byproducts that are both beneficial and detrimental.  For example, we cannot readily digest resistant starches and fiber, leaving them for our gut microbes.  They consume these carbohydrates and produce short chain fatty acids (SCFAs), which are an energy source for the cells lining the large intestine.  These SCFAs also have been shown to regulate inflammation and even to help fight off pathogenic bacteria.  In contrast, bacterial fermentation of a subclass of amino acids produces toxic hydrogen sulfide and aromatic compounds (phenols and indoles).  Our liver and kidneys, if functioning properly, neutralize these toxins.  However, these compounds are linked to diseases such as ulcerative colitis and inflammatory bowel disease.

            Protein sources contain other molecules besides proteins and amino acids that have been shown to have adverse health effects.  Choline, a byproduct of a lipid found in plants and animals, is converted by our gut microbiota into trimethylamine (TMA).  Once TMA is absorbed into our liver, it can be oxidized to form trimethylamine-N-oxide (TMAO), which is then released into the bloodstream.  A high concentration of blood plasma TMAO is correlated with cardiovascular disease.  Recently, L-carnitine has also been shown to be converted to TMA and thus TMAO by gut bacteria.  L-carnitine (a compound synthesized from the two amino acids lysine and methionine) is found in high levels in red meat.  However, increased L-carnitine in the blood was only correlated with increased risk of cardiovascular disease when accompanied by high levels of TMAO, which suggests that only when bacteria that can degrade L-carnitine to TMA are present, is there an increased risk of atherosclerosis.

            The CrossFit community is not the only group increasing their protein intake.  With the popularity of the Atkins and Paleo diets, many Americans have shifted their focus from low-fat foods to consuming more protein.  Although these diets seem to help people lose weight, overconsumption of protein may result in the production of toxic compounds with detrimental effects.  After an intense workout, the body requires amino acids in order to rebuild muscle.  Therefore, the post-workout recovery shake is most likely beneficial.  However, chronic overconsumption of protein may indeed lead to an increased risk of cardiovascular and gastrointestinal diseases.  Only more research and time will tell, but until then perhaps I should only buy protein shakes formulated specifically for women.

Further Reading:

Daily Recommended Protein Intake:

http://books.nap.edu/openbook.php?record_id=10490&page=R1

http://www.cdc.gov/nutrition/everyone/basics/protein.html#How%20much%20protein

Protein metabolism/catabolism:

http://en.wikipedia.org/wiki/Protein_%28nutrient%29

http://www.nature.com/scitable/topicpage/nutrient-utilization-in-humans-metabolism-pathways-14234029

http://pharmaxchange.info/press/2013/07/digestion-of-dietary-proteins-in-the-gastro-intestinal-tract-gi-tract/

Gut microbiota and protein metabolism:

Russell WR et al. Colonic bacterial metabolites and human health.  2013.  Curr Opin Microbiol. 3: 246-54

Nyangale EP et al. Gut Microbial Activity, Implications for Health and Disease: The Potential Role of Metabolite Analysis. 2012. J. Proteome Res. 12: 5573-5585

Willyard C. Pathology: At the heart of the problem. 2013. Nature 493: S10-11

Koeth RA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. 2013. Nat Med. 19: 576-585