Viruses living in the gut

February 8th, 2015 by Marta Wegorzewska, PhD

This is a story of a dear friend, ulcerative colitis and viruses.

First year of graduate school taught me that ulcerative colitis is a very complex disease involving the colon and rectum, bacteria, an immune system and a lot of questions to which we don’t have any answers to yet. For years that is all I knew about colitis. At that point in my education, colitis was nothing more than a devastating disease and a lot of fascinating questions.

A few years later, I met a student and we naturally became friends. We went to Zumba together, spent our weekends shopping downtown and enjoyed many delicious meals. As we grew closer, I got to sample her life as she sampled mine. I met her significant other, her family, her pet. I also met colitis.

The gut houses diverse populations of bacterial communities. When certain communities are disrupted while others become more prevalent, disease can occur. This is the scientific basis for ulcerative colitis.

It was Thursday at 6pm. We wrapped up our research for the day and headed to our favorite Zumba class. It was just another regular day. We were two happy twenty-something year olds looking forward to our favorite exercise class. We joked about the small things that annoyed us that day while we changed into our Zumba shoes.

Anyone that saw the two of us together would have never guessed that my friend was going to have a flare-up during this class. She left early and I found her sitting in the locker room in the fetal position. Bloody diarrhea was her primary symptom. She was experiencing inflammation in the colon.

The next few days we spent our lunch breaks discussing what could have caused her colon to get inflamed. We are scientists after all; we should be able to figure it out. But we couldn’t. Her life was no different from mine. At times her life was full of euphoria and excitement and other times full of stress. But we are different. She suffers from ulcerative colitis.

Those who suffer from ulcerative colitis have disruptions in the bacterial communities that house the gut. How that translates to disease we still do not know but it is an interesting question in itself as to why those changes occur. In other words, what causes lose of certain populations of bacteria living in the gut?

A group of scientists at Washington University in St Louis have an interesting idea as to why populations of bacterial in the gut may have gone missing. They wondered whether viruses that also reside in the gut may be causing changes in the bacterial communities in the gut. A specific type of viruses called bacteriophages can infect bacteria and eliminate them. These scientists made the interesting observation that people suffering from ulcerative colitis have different and more numerous populations of bacteriophages in their gut that coincided with a loss of certain populations of bacteria. They published their findings last month in Cell, Host and Microbe.

Before we continue this story, I caution you that although these scientists think that viruses may be affecting the community of bacteria that live in the gut, they have not yet proven that it exactly what is happening. They found a connection between the presence of certain viruses that coincide with the absence of certain bacteria. The next question is, are these viruses killing the bacteria that have gone missing? And is this causing colitis? They do not know yet. Nevertheless, it is an interesting observation that may hint at what is going on. It is very well possible that next month you will hear the story of how bacteriophages present in the gut are killing bacteria that are needed to protect against colitis.

Let’s pretend that indeed viruses are causing colitis! If ulcerative colitis can be triggered by a virus, is it contagious? We all have experienced the flu virus and know that if someone at work has the flu, there is a good chance you will get it too. But we also know some viruses, like the flu, are more contagious than others, like Ebola. Depending on how they are transmitted, some viruses are more contagious (airborne viruses) than others (spread through bodily fluids). As far as I can tell, nobody knows. People with ulcerative colitis live with family members that do not have the disease so perhaps it is not transmittable. Whatever the role of these viruses is, I wonder how the viruses getting there and why are only certain people susceptible to their infection?

What do you think? What do you know about viruses and colitis?

Passing Down Healthy Paternal Genes, One Green Leafy Vegetable At A Time

Every woman dreams about giving birth to a healthy baby. A new study shows men who eat their green leafy vegetables can make those dreams come true.

In the study published in Nature Communications, researchers from McGill University in Montreal led by Dr. Kimmins found a father’s diet before conception has consequences for his baby’s health, at least in mice.

The scientists focused on folate, found in green leafy vegetables such as kale and spinach. Male mice were fed a folate-sufficient or a folate-deficient diet throughout life. The two groups of mice initially appeared identical because no effect on testes or sperm development was found.

But when the different males were mated with folate-sufficient females, the scientists made a striking observation. The females paired with males fed a folate-deficient diet had a difficult time becoming pregnant. If the females conceived, the offspring had an almost 30% increase in birth defects affecting development of their muscles and bones.

“Despite the fact that folic acid is now added to a variety of foods, fathers who are eating high-fat, fast food diets or who are obese may not be able to use or metabolize folate in the same way as those with adequate levels of the vitamin,” says Dr. Kimmins. The inability to metabolize folate, the scientists think, translates to infertility and birth defects in mice.

Folate is a rich source of organic methyl groups. Methyl groups, composed of carbon and hydrogen atoms, attach to DNA. The DNA is an instruction manual; it determines if a cell becomes a nose, kidney or bone cell. Each page of the manual is a different gene with a unique set of instructions. With so many pages, how does a cell know what to listen to? Methyl groups attach to certain genes to stop them from being read. For a cell destined to become a bone cell, only genes involved in bone cell development are fee of methyl groups. If not enough methyl groups are available because of a lack of folate, too many pages are read and the cell receives mixed messages. The cell’s confusion manifests into a developmental defect.

The importance of folate for pregnancy is nothing new, but the focus has always been on women. Women planning to become pregnant are already advised to take vitamins containing folate to prevent miscarriages and birth defects such as spina bifida, the incomplete development of the spinal cord. This is the first study to bring awareness to the contribution a father’s diet has on the health of his baby. It also points out the need to extend preconception counseling to men planning to have children.

It makes sense for a woman’s diet to affect the baby depending on her for nutrients during pregnancy. How can a father’s diet affect a baby’s development if he does not come into contact with the baby in utero? The answer, scientists think, lies hidden in the sperm.

The sperm’s genetic material actually carries a memory of a father’s dietary history. The genetic material in the sperm of mice fed a diet deficient in folate was improperly labeled with methyl groups. It was once thought the methylation pattern was erased from one generation to the next preventing inheritance of our predecessor’s bad eating habits. But scientists made the surprising discovery that history repeats itself. The offspring of male mice fed a diet deficient in folate inherited the mislabeled genetic material. A closer look revealed the genes affected include those implicated in development as well as cancer, diabetes, autism and schizophrenia.

But diet is not the only environmental factor affecting our genes. Our predecessor’s hardships and good fortunes can also leave molecular memories on DNA. Once inherited, they affect our psychology and behavior. You inherited a remarkable ability to bounce back from hardship because your parents grew up in loving homes. You can thank your grandparents for this gift.

We live in an age where fast food has revolutionized how we eat. Cheap and easy food has eliminated the incentive to cook healthy meals. It is no surprise our dietary decisions affect our health. We are often reminded, “we are what we eat.” The result is a worldwide obesity problem not only affecting our own health but that of generations to come.

You may be wondering how many servings of green leafy vegetables to eat a day to see an effect. It is still unclear how the findings in mice will translate to humans but to ensure the health of their future children, men should consider changing their lifestyles, one green leafy vegetable at a time.

Are you mindful of your pregnant mind?

April 14, 2014. Dr. Marta Wegorzewska, PhD , in collaboration with Dr. Seth Bokser, MD.

I am terrified of giving birth one day. As a twenty-eight year old woman who is planning to have a child in the foreseeable future, giving birth is number one on my list of irrational fears. Can’t my partner do it? He is better at handling pain anyway.

This fear lurks in my mind. I often browse Facebook pages of friends who have succeeded in giving birth to convince myself it is indeed possible. In doing so, I recently discovered a Tedx Talk by Ina May Gaskin, mother of midwifery, who describes a culture of fear surrounding childbirth in the US. I am not alone?

It is no secret that labor is painful. Stories get passed down through generations and linger in every woman’s mind. The due date becomes a moving target. Minutes fall off rapidly from the clock. Time moves faster towards the things we fear most.

As the mind races to acknowledge its fears of the uncontrollable future, the present moment passes by unnoticed. The remarkable finite experience of pregnancy is left unexplored.

Mindfulness, rooted in Buddhism and adopted in the West by Jon Kabat-Zin, PhD, is the practice of paying attention to the present moment without judgment while letting go of thoughts about the past or anxieties about the future.1

In the present moment, a pregnant woman’s body undergoes daily changes. A being grows inside her, dependent on her for nutrients and protection. Stop and take a second to think about that—for nine months a woman houses another being inside her body. The biology of pregnancy is remarkably complex, a complexity full of fascinating mysteries. Its beauty captured by an Argentinian photographer.

The mind can in fact be trained to be present. Mindfulness practice has been scientifically proven to reduce stress, improve psychological well-being, help with anxiety and depression and improve immune function in adults.2-7

Mindfulness practice uses guided meditation and yoga practices to observe thoughts, feelings and emotions without judgment as they appear in the present moment. Nancy Bardacke, RN, CNM, MA developed a 10-session Mindfulness-Based Childbirth and Parenting program (MBCP) to help parents-to-be work with the stress, anxiety and fear that for many are a normal process in the transition into parenthood.

The study of the efficacy of mindfulness-based practices during pregnancy, childbirth is in its infancy. However, early studies are beginning to show a reduction in anxiety, worry and depression among pregnant women who participate in mindfulness practice during pregnancy.8-10

Individuals who report improvement in psychological well-being after mindfulness practice appear to have changes in areas of the brain that are associated with arousal and mood.11 Scientists are also learning that meditation, a component of mindfulness practice, is able to change how certain genes get expressed.12 The expression of these genes affects how quickly we recover from stress and how we perceive pain.12

For all parents-to-be, there is never enough time to prepare for the future. The baby’s room needs to be painted, his name chosen and baby books read. Experiencing pregnancy in the present moment, however, may help prepare a woman for childbirth without fear. As fear subsides, the excitement of welcoming a child into the world dampens the pain of childbirth.

What should you do if you have feelings of fear about your due date?

Be prepared. Know what to expect on the day you deliver. If you know what is coming, it will appear more familiar when it happens.

Practice yoga and/or meditation. Take time out of your schedule to be present in the moment.

Learn about mindfulness. Read about how mindful birthing can help you through your delivery.

Consider participating in MBCP. Meet others who may share your feelings around childbirth.

This post was checked by the following science articles:

1. Williams, JMG.; Teasdale, JD.; Segal, ZV.; Kabat-Zinn, J. The mindful way through depression: Freeing yourself from chronic unhappiness. New York:Gilford; 2007.

2. Astin JA. Stress reduction through mindfulness meditation: Effects on psychological symptomology, sense of control, and spiritual experiences. Psychotherapy and Psychosomatics. 1997;66:97–106.

3. Davidson RJ, Kabat-Zinn J, Schumacher J, Rosenkranz M, Muller D, Santorelli S, et al. Alterations in brain and immune function produced by mindfulness meditation. Psychosomatic Medicine. 2003;65:564–570.

4. Segal ZV, Williams JMG, Teasdale JD. Mindfulness-based cognitive therapy for depression. New York: The Guilford Press; 2002.

5. Shapiro SL, Schwartz GE, Bonner G. Effects of mindfulness-based stress reduction on medical and premedical students. Journal of Behavioral Medicine. 1998;139:267–274.

6. Speca M, Carlson LE, Goodey E, Angen M. A randomized, wait-list controlled trial: The effect of a mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients. Psychosomatic Medicine. 2000;62:613–622.

7. Williams KA, Kolar MM, Reger BE, Pearson JC. Evaluation of a wellness-based mindfulness stress reduction intervention: A controlled trial. American Journal of Health Promotion. 2001;15:422–432.

8. Duncan LG, Bardacke N. Mindfulness-Based Childbirth and Parenting Education: Promoting Family Mindfulness During the Perinatal Period. J Child Fam Stud. 2010 Apr;19(2):190-202.

9. Goodman JH, Guarino A, Chenausky K, Klein L, Prager J, Petersen R, Forget A, Freeman M. CALM Pregnancy: results of a pilot study of mindfulness-based cognitive therapy for perinatal anxiety. Arch Womens Ment Health. 2014 Jan 22.

10. Guardino CM, Dunkel Schetter C, Bower JE, Lu MC, Smalley SL. Randomised controlled pilot trial of mindfulness training for stress reduction during pregnancy. Psychol Health. 2014;29(3):334-49.

11. Singleton O, Hölzel BK, Vangel M, Brach N, Carmody J, Lazar SW. Change in Brainstem Gray Matter Concentration Following a Mindfulness-Based Intervention is Correlated with Improvement in Psychological Well-Being. Front Hum Neurosci. 2014 Feb 18;8:33.

Are Phthalates In The Home Putting Babies At Risk For Premature Birth?

December 17, 2013. Marta Wegorzewska, PhD candidate, in collaboration with Dr. Seth Bokser, MD.

There was a time you lived in your mother’s uterus. You do not remember it, but it was a memorable time.

Often, that time is nine months long. The nine-month period ensures the fetus is developmentally ready for a new stage in life—babyhood. Babyhood requires lungs that breathe, a stomach that digests milk and an immune system that fights bugs. Until birth, the mother performs these tasks for the fetus.

Some fetuses transition into babyhood before they are prepared for this new stage in life. These babies are called premature babies or preemies. Scientists learned pregnant women who give birth to preemies are more likely to be exposed to environmental contaminants called phthalates.1

Phthalates are chemical added to plastics (shower curtains, rainwear, toys etc)2 to help soften them. Phthalates are also added to personal-care products including soap, shampoo, lotion and deodorant.3 Most people, including pregnant women, unintentionally encounter phthalates regularly in their environment.

Over time, phthalates leak out of plastics and contaminate the food and water we ingest.4 People can also come into contact with phthalates when they apply products containing the chemicals onto their skin.3

A recent case-control study1 identified a correlation between exposure to phthalates during pregnancy and premature delivery of the baby. It showed women who went into labor too early had higher levels of phthalates in their urine.1 This was the largest study done on phthalates and premature birth to date. This study does not prove phthalates cause babies to be born too early, but it provides reason for scientists to study causation in the future.

Preterm labor occurs when babies are born before 37 weeks’ gestation.5 It is a major problem worldwide, and the greatest contributor to neonatal morbidity and mortality.6 Babies born too early have problems breathing, eating and fighting infections due to underdeveloped lungs, intestines and immune system, respectively.6

The current thought on why labor happens too soon is that inflammation in the uterine environment triggers the production of prostaglandins.5,7 Prostaglandins are hormones that start labor.7 Because phthalates are also linked to inflammation8 scientists wonder if phthalates can trigger prostaglandin production and early delivery.

There is no evidence at this time implicating phthalates as a cause for preterm labor. But there is also no benefit to being exposed to phthalates. If you chose to limit your exposure to phthalates, here are a few things you can do:

1. Read labels. Phthalate is a general term for a class of chemicals included in plastics and personal-care products. Look for the following chemical names and/or abbreviations:

DEHP (di-2-ethylhexyl phthalate)
MECPP (mono-(2-ehtyl-5-carboxypentyl) phthalate)
MEHP (mono-(2-ehtyl)-hexyl phthalate)
MBP (mono-n-butyl phthalate)
MEOHP (mono-(2-ethyl-5-oxohexyl) phthalate)
MCPP (mono-(3-carboxypropyl) phthalate)

2. Know your plastics. Choose plastics with the recycling code 1, 2 or 5. Recycling codes 3 and 7 are more likely to contain phthalates.

3. Avoid plastic and heat. Switch to glass when heating your food in the microwave. Avoid covering your food with plastic wrap. Use paper towels instead.

Do your personal care products contain phthalates? Check today!

This work is funded in part by the Graduate Student Internships for Career Exploration (GSICE) program at UCSF

This post was checked by the following science articles:

1) Ferguson KK, McElrath TF, Meeker JD. 2013. Environmental Phthalate Exposure and Preterm Birth. JAMA Pediatr. Online.

2) Fromme H, Gruber L, Schlummer M, Wolz G, Böhmer S, Angerer J, Mayer R, Liebl B, Bolte G. 2007. Intake of phthalates and di(2-ethylhexyl)-adipate: Results of the Integrated Exposure Assessment Survey based on duplicate diet samples and biomonitoring data. Environ. Int 33: 1012–1020

3) ATSDR. Toxicological profile for diethylphthalate, U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA, 1995.

4) ATSDR. Toxicological profile for di(2-ethylhexyl)phthalate (DEHP), U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA, 2002.

5) Goldenberg RL, Culhane JF, Iams JD, Romero R. 2008. Epidemiology and causes of preterm birth. Lancet 371:75-84.

6) McCormick MC. 1985. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 312: 82–90

7) Goldenberg RL, Hauth JC, Andrews WW. 2000. Intrauterine infection and preterm delivery. N Engl J Med 342:1500–1507

8) Ferguson KK, Loch-Caruso R, Meeker JD. 2012. Exploration of oxidative stress and inflammatory markers in relation to urinary phthalate metabolites: NHANES 1999-2006. Environ Sci Technol 46: 477-85.

The Cloak of Invisibility

December 6, 2013. Marta Wegorzewska, PhD candidate.

We learned that fetal DNA can be found in the mother’s blood. Companies are using this finding to create new prenatal screening tests. This finding also raises some interesting questions we will examine in a two part series.

Once the fetal DNA is swimming in the mother’s blood, does the mother’s immune system know it is there?

A baby receives half of her DNA from her mother and half from her father. The DNA from her father, different from her mother’s, should alarm the mother’s immune system a foreigner is present.

The mother’s immune system is made of troops that defend against invading bacteria, viruses, and cancer. They could attack the fetus, but they do not. Why not?

Nature has developed multiple ways to protect the fetus from the mother’s immune system.

Fetal DNA wears a cloak of invisibility.1 It goes unnoticed when passing surveilling troops in the mother’s blood. If the cloak of invisibility slips off, the fetus gets help from the mother’s immune system!

Wait! The mother’s immune system can harm and protect the fetus at the same time?

You guessed it! The mother’s immune system can also protect the fetus. Regulatory officers oversee the surveilling troops. In some cases, the officers can stop the troops from attacking the fetus. The officers can only help the fetus when fetal DNA is found in very small amounts in the mother’s blood (as is the case during healthy pregnancy). An excess of fetal DNA may be responsible, scientists think, for problems during pregnancy.2

Now it is your turn to be a scientist.

Companies are using the finding that fetal DNA is swimming in the mother’s blood to create tests that screen fetal DNA for genetic abnormalities. But that is not the reason why nature allowed for this phenomenon to evolve. Can you come up with a reason as to why nature allows fetal DNA to swim in the mother’s blood knowing that the mother’s immune system could potentially see that DNA and harm the fetus?

There is no wrong answer. Nobody knows!

My guess is that by exposing the mother to small doses of fetal DNA (remember fetal DNA is found in the mother’s blood in very small amounts), her immune system learns the fetus is not an invader but a welcomed guest. What is your guess?

This work is funded in part by the Graduate Student Internships for Career Exploration (GSICE) program at UCSF

This post is checked by the following science articles:

1. Madeja, Z., H. Yadi, R. Apps, S. Boulenouar, S. J. Roper, L. Gardner, A. Moffett, F. Colucci, and M. Hemberger. 2011. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci 108: 4012-4017.

2. Saadai, P., T. H. Lee, G. Bautista, K. D. Gonzales, A. Nijagal, M. P. Busch, C. J. Kim, R. Romero, H. Lee, S. Hirose, L. Rand, D. Miniati, D. L. Farmer, and T. C. Mackenzie. 2012. Alterations in maternal-fetal cellular trafficking after fetal surgery. J Peds Surg 47: 1089-1094.