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Could A Gut-Brain Connection Help Explain Autism?

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What is Your Big Idea?
Diego Bohórquez/Credit: Duke University, Durham, NC

You might think nutrient-sensing cells in the human gastrointestinal (GI) tract would have no connection whatsoever to autism spectrum disorder (ASD). But if Diego Bohórquez’s “big idea” is correct, these GI cells, called neuropods, could one day help to provide a direct link into understanding and treating some aspects of autism and other brain disorders.

Bohórquez, a researcher at Duke University, Durham, NC, recently discovered that cells in the intestine, previously known for their hormone-releasing ability, form extensions similar to neurons. He also found that those extensions connect to nerve fibers in the gut, which relay signals to the vagus nerve and onward to the brain. In fact, he found that those signals reach the brain in milliseconds [1].

Bohórquez has dedicated his lab to studying this direct, high-speed hookup between gut and brain and its impact on nutrient sensing, eating, and other essential behaviors. Now, with support from a 2019 NIH Director’s New Innovator Award, he will also explore the potential for treating autism and other brain disorders with drugs that act on the gut.

Bohórquez became interested in autism and its possible link to the gut-brain connection after a chance encounter with Geraldine Dawson, director of the Duke Center for Autism and Brain Development. Dawson mentioned that autism typically affects multiple organ systems.

With further reading, he discovered that kids with autism frequently cope with GI issues, including bowel inflammation, abdominal pain, constipation, and/or diarrhea [2]. They often also show unusual food-related behaviors, such as being extremely picky eaters. But his curiosity was especially piqued by evidence that certain gut microbes can influence abnormal behaviors in mice that model autism.

With his New Innovator Award, Bohórquez will study neuropods and the gut-brain connection in a mouse model of autism. Using the tools of optogenetics, which make it possible to activate cells with light, he’ll also see whether autism-like symptoms in mice can be altered or alleviated by controlling neuropods in the gut. Those symptoms include anxiety, repetitive behaviors, and lack of interest in interacting with other mice. He’ll also explore changes in the animals’ eating habits.

In another line of study, he will take advantage of intestinal tissue samples collected from people with autism. He’ll use those tissues to grow and then examine miniature intestinal “organoids,” looking for possible evidence that those from people with autism are different from others.

For the millions of people now living with autism, no truly effective drug therapies are available to help to manage the condition and its many behavioral and bodily symptoms. Bohórquez hopes one day to change that with drugs that act safely on the gut. In the meantime, he and his fellow “GASTRONAUTS” look forward to making some important and fascinating discoveries in the relatively uncharted territory where the gut meets the brain.

References:

[1] A gut-brain neural circuit for nutrient sensory transduction. Kaelberer MM, Buchanan KL, Klein ME, Barth BB, Montoya MM, Shen X, Bohórquez DV. Science. 2018 Sep 21;361(6408).

[2] Association of maternal report of infant and toddler gastrointestinal symptoms with autism: evidence from a prospective birth cohort. Bresnahan M, Hornig M, Schultz AF, Gunnes N, Hirtz D, Lie KK, Magnus P, Reichborn-Kjennerud T, Roth C, Schjølberg S, Stoltenberg C, Surén P, Susser E, Lipkin WI. JAMA Psychiatry. 2015 May;72(5):466-474.

Links:

Autism Spectrum Disorder (National Institute of Mental Health/NIH)

Bohórquez Lab (Duke University, Durham, NC)

Bohórquez Project Information (NIH RePORTER)

NIH Director’s New Innovator Award (Common Fund)

NIH Support: Common Fund; National Institute of Mental Health


Celebrating 2019 Biomedical Breakthroughs

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Science 2019 Biomedical Breakthroughs and a Breakdown

Happy New Year! As we say goodbye to the Teens, let’s take a look back at 2019 and some of the groundbreaking scientific discoveries that closed out this remarkable decade.

Each December, the reporters and editors at the journal Science select their breakthrough of the year, and the choice for 2019 is nothing less than spectacular: An international network of radio astronomers published the first image of a black hole, the long-theorized cosmic singularity where gravity is so strong that even light cannot escape [1]. This one resides in a galaxy 53 million light-years from Earth! (A light-year equals about 6 trillion miles.)

Though the competition was certainly stiff in 2019, the biomedical sciences were well represented among Science’s “runner-up” breakthroughs. They include three breakthroughs that have received NIH support. Let’s take a look at them:

In a first, drug treats most cases of cystic fibrosis: Last October, two international research teams reported the results from phase 3 clinical trials of the triple drug therapy Trikafta to treat cystic fibrosis (CF). Their data showed Trikafta effectively compensates for the effects of a mutation carried by about 90 percent of people born with CF. Upon reviewing these impressive data, the Food and Drug Administration (FDA) approved Trikafta, developed by Vertex Pharmaceuticals.

The approval of Trikafta was a wonderful day for me personally, having co-led the team that isolated the CF gene 30 years ago. A few years later, I wrote a song called “Dare to Dream” imagining that wonderful day when “the story of CF is history.” Though we’ve still got more work to do, we’re getting a lot closer to making that dream come true. Indeed, with the approval of Trikafta, most people with CF have for the first time ever a real chance at managing this genetic disease as a chronic condition over the course of their lives. That’s a tremendous accomplishment considering that few with CF lived beyond their teens as recently as the 1980s.

Such progress has been made possible by decades of work involving a vast number of researchers, many funded by NIH, as well as by more than two decades of visionary and collaborative efforts between the Cystic Fibrosis Foundation and Aurora Biosciences (now, Vertex) that built upon that fundamental knowledge of the responsible gene and its protein product. Not only did this innovative approach serve to accelerate the development of therapies for CF, it established a model that may inform efforts to develop therapies for other rare genetic diseases.

Hope for Ebola patients, at last: It was just six years ago that news of a major Ebola outbreak in West Africa sounded a global health emergency of the highest order. Ebola virus disease was then recognized as an untreatable, rapidly fatal illness for the majority of those who contracted it. Though international control efforts ultimately contained the spread of the virus in West Africa within about two years, over 28,600 cases had been confirmed leading to more than 11,000 deaths—marking the largest known Ebola outbreak in human history. Most recently, another major outbreak continues to wreak havoc in northeastern Democratic Republic of Congo (DRC), where violent civil unrest is greatly challenging public health control efforts.

As troubling as this news remains, 2019 brought a needed breakthrough for the millions of people living in areas susceptible to Ebola outbreaks. A randomized clinical trial in the DRC evaluated four different drugs for treating acutely infected individuals, including an antibody against the virus called mAb114, and a cocktail of anti-Ebola antibodies referred to as REGN-EB3. The trial’s preliminary data showed that about 70 percent of the patients who received either mAb114 or the REGN-EB3 antibody cocktail survived, compared with about half of those given either of the other two medicines.

So compelling were these preliminary results that the trial, co-sponsored by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the DRC’s National Institute for Biomedical Research, was halted last August. The results were also promptly made public to help save lives and stem the latest outbreak. All Ebola patients in the DRC treatment centers now are treated with one or the other of these two options. The trial results were recently published.

The NIH-developed mAb114 antibody and the REGN-EB3 cocktail are the first therapeutics to be shown in a scientifically rigorous study to be effective at treating Ebola. This work also demonstrates that ethically sound clinical research can be conducted under difficult conditions in the midst of a disease outbreak. In fact, the halted study was named Pamoja Tulinde Maisha (PALM), which means “together save lives” in Kiswahili.

To top off the life-saving progress in 2019, the FDA just approved the first vaccine for Ebola. Called Ervebo (earlier rVSV-ZEBOV), this single-dose injectable vaccine is a non-infectious version of an animal virus that has been genetically engineered to carry a segment of a gene from the Zaire species of the Ebola virus—the virus responsible for the current DRC outbreak and the West Africa outbreak. Because the vaccine does not contain the whole Zaire virus, it can’t cause Ebola. Results from a large study in Guinea conducted by the WHO indicated that the vaccine offered substantial protection against Ebola virus disease. Ervebo, produced by Merck, has already been given to over 259,000 individuals as part of the response to the DRC outbreak. The NIH has supported numerous clinical trials of the vaccine, including an ongoing study in West Africa.

Microbes combat malnourishment: Researchers discovered a few years ago that abnormal microbial communities, or microbiomes, in the intestine appear to contribute to childhood malnutrition. An NIH-supported research team followed up on this lead with a study of kids in Bangladesh, and it published last July its groundbreaking finding: that foods formulated to repair the “gut microbiome” helped malnourished kids rebuild their health. The researchers were able to identify a network of 15 bacterial species that consistently interact in the gut microbiomes of Bangladeshi children. In this month-long study, this bacterial network helped the researchers characterize a child’s microbiome and/or its relative state of repair.

But a month isn’t long enough to determine how the new foods would help children grow and recover. The researchers are conducting a similar study that is much longer and larger. Globally, malnutrition affects an estimated 238 million children under the age 5, stunting their normal growth, compromising their health, and limiting their mental development. The hope is that these new foods and others adapted for use around the world soon will help many more kids grow up to be healthy adults.

Measles Resurgent: The staff at Science also listed their less-encouraging 2019 Breakdowns of the Year, and unfortunately the biomedical sciences made the cut with the return of measles in the U.S. Prior to 1963, when the measles vaccine was developed, 3 to 4 million Americans were sickened by measles each year. Each year about 500 children would die from measles, and many more would suffer lifelong complications. As more people were vaccinated, the incidence of measles plummeted. By the year 2000, the disease was even declared eliminated from the U.S.

But, as more parents have chosen not to vaccinate their children, driven by the now debunked claim that vaccines are connected to autism, measles has made a very preventable comeback. Last October, the Centers for Disease Control and Prevention (CDC) reported an estimated 1,250 measles cases in the United States at that point in 2019, surpassing the total number of cases reported annually in each of the past 25 years.

The good news is those numbers can be reduced if more people get the vaccine, which has been shown repeatedly in many large and rigorous studies to be safe and effective. The CDC recommends that children should receive their first dose by 12 to 15 months of age and a second dose between the ages of 4 and 6. Older people who’ve been vaccinated or have had the measles previously should consider being re-vaccinated, especially if they live in places with low vaccination rates or will be traveling to countries where measles are endemic.

Despite this public health breakdown, 2019 closed out a memorable decade of scientific discovery. The Twenties will build on discoveries made during the Teens and bring us even closer to an era of precision medicine to improve the lives of millions of Americans. So, onward to 2020—and happy New Year!

Reference:

[1] 2019 Breakthrough of the Year. Science, December 19, 2019.

NIH Support: These breakthroughs represent the culmination of years of research involving many investigators and the support of multiple NIH institutes.


Americans Are Still Eating Too Much Added Sugar, Fat

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Foods with refined grains and sugar
Credit: iStock/happy_lark

Most of us know one of the best health moves we can make is to skip the junk food and eat a nutritious, well-balanced diet. But how are we doing at putting that knowledge into action? Not so great, according to a new analysis that reveals Americans continue to get more than 50 percent of their calories from low-quality carbohydrates and artery-clogging saturated fat.

In their analysis of the eating habits of nearly 44,000 adults over 16 years, NIH-funded researchers attributed much of our nation’s poor dietary showing to its ongoing love affair with heavily processed fast foods and snacks. But there were a few bright spots. The analysis also found that, compared to just a few decades ago, Americans are eating more foods with less added sugar, as well as more whole grains (e.g., brown rice, quinoa, rolled oats), plant proteins (e.g., nuts, beans), and sources of healthy fats (e.g., olive oil).

Over the last 20-plus years, research has generated new ideas about eating a proper diet. In the United States, the revised thinking led to the 2015-2020 Dietary Guidelines for Americans. They recommend eating more fruits, vegetables, whole grains, and other nutrient-dense foods, while limiting foods containing added sugars, saturated fats, and salt.

In the report published in JAMA, a team of researchers wanted to see how Americans are doing at following the new guidelines. The team was led by Shilpa Bhupathiraju, Harvard T. H. Chan School of Public Health, Boston, and Fang Fang Zhang, Tufts University, Boston.

To get the answer, the researchers looked to the National Health and Nutrition Examination Survey (NHANES). The survey includes a nationally representative sample of U.S. adults, age 20 or older, who had answered questions about their food and beverage intake over a 24-hour period at least once during nine annual survey cycles between 1999-2000 and 2015-2016.

The researchers assessed the overall quality of the American diet using the Healthy Eating Index-2015 (HEI-2015), which measures adherence to the 2015-2020 Dietary Guidelines. The HEI-2015 scores range from 0 to 100, with the latter number being a perfect, A-plus score. The analysis showed the American diet barely inching up over the last two decades from a final score of 55.7 to 57.7.

That, of course, is still far from a passing grade. Some of the common mistakes identified:

• Refined grains, starchy vegetables, and added sugars still account for 42 percent of the average American’s daily calories.
• Whole grains and fruits provide just 9 percent of daily calories.
• Saturated fat consumption remains above 10 percent of daily calories, as many Americans continue to eat more red and processed meat.

Looking on the bright side, the data do indicate more Americans are starting to lean toward the right choices. They are getting slightly more of their calories from healthier whole grains and a little less from added sugar. Americans are also now looking a little more to whole grains, nuts, and beans as a protein source. It’s important to note, though, these small gains weren’t seen in lower income groups or older adults.

The bottom line is most Americans still have an awfully long way to go to shape up their diets. The question is: how to get there? There are plenty of good choices that can help to turn things around, from reading food labels and limiting calories or portion sizes to exercising and finding healthy recipes that suit your palate.

Meanwhile, nutrition research is poised for a renaissance. Tremendous progress is being made in studying the microbial communities, or microbiomes, helping to digest our foods. The same is true for studies of energy metabolism, genetic variation influencing our dietary preferences, and the effects of aging.

This is an optimum time to enhance the science and evidence base for human nutrition. That may result in some updating of the scoring system for the nation’s dietary report card. But it will be up to all of us to figure out how to ace it.

References:

[1] Trends in Dietary Carbohydrate, Protein, and Fat Intake and Diet Quality Among US Adults, 1999-2016. Shan Z, Rehm CD, Rogers G, Ruan M, Wang DD, Hu FB, Mozaffarian D, Zhang FF, Bhupathiraju SN. JAMA. 2019 Sep 24;322(12):1178-1187.

Links:

Eat Right (National Heart, Lung, and Blood Institute/NIH)

Dietary Fats (MedlinePlus, National Library of Medicine/NIH)

ChooseMyPlate (U.S. Department of Agriculture)

Healthy Eating Index (Department of Agriculture)

NIH Nutrition Research Task Force (National Institute of Diabetes and Digestive and Kidney Disease/NIH)

Dietary Guidelines for Americans (U.S. Department of Health and Human Services)

Shilpa Bhupathiraju (Harvard T. H. Chan School of Public Health, Boston)

Fang Fang Zhang (Tufts University, Boston)

NIH Support: National Institute on Minority Health and Health Disparities; National Institute of Diabetes and Digestive and Kidney Diseases


Targeting the Microbiome to Treat Malnutrition

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Caption: A Bangladeshi mother and child in the Nutritional Rehabilitation Unit.
Credit: International Centre for Diarrhoeal Disease Research, Bangladesh

A few years ago, researchers discovered that abnormalities in microbial communities, or microbiomes, in the intestine appear to contribute to childhood malnutrition. Now comes word that this discovery is being translated into action, with a new study showing that foods formulated to repair the “gut microbiome” may help malnourished kids rebuild their health [1].

In a month-long clinical trial in Bangladesh, 63 children received either regular foods to treat malnutrition or alternative formulations for needed calories and nutrition that also encouraged growth of beneficial microbes in the intestines. The kids who ate the microbiome-friendly diets showed improvements in their microbiome, which helps to extract and metabolize nutrients in our food to help the body grow. They also had significant improvements in key blood proteins associated with bone growth, brain development, immunity, and metabolism; those who ate standard therapeutic food did not experience the same benefit.

Globally, malnutrition affects an estimated 238 million children under the age 5, stunting their normal growth, compromising their health, and limiting their mental development [2]. Malnutrition can arise not only from a shortage of food but from dietary imbalances that don’t satisfy the body’s need for essential nutrients. Far too often, especially in impoverished areas, the condition can turn extremely severe and deadly. And the long term effects on intellectual development can limit the ability of a country’s citizens to lift themselves out of poverty.

Jeffrey Gordon, Washington University School of Medicine in St. Louis, and his NIH-supported research team have spent decades studying what constitutes a normal microbiome and how changes can affect health and disease. Their seminal studies have revealed that severely malnourished kids have “immature” microbiomes that don’t develop in the intestine like the microbial communities seen in well nourished, healthy children of the same age.

Gordon and team have also found that this microbial immaturity doesn’t resolve when kids consume the usual supplemental foods [3]. In another study, they turned to mice raised under sterile conditions and with no microbes of their own to demonstrate this cause and effect. The researchers colonized the intestines of the germ-free mice with microbes from malnourished children, and the rodents developed similar abnormalities in weight gain, bone growth, and metabolism [4].

All of this evidence raised a vital question: Could the right combination of foods “mature” the microbiome and help to steer malnourished children toward a healthier state?

To get the answer, Gordon and his colleagues at the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh, led by Tahmeed Ahmed, first had to formulate the right, microbiome-friendly food supplements, and that led to some interesting science. They carefully characterized over time the immature microbiomes found in Bangladeshi children treated for severe malnutrition. This allowed them to test their new method for analyzing how individual microbial species fluctuate over time and in relationship to one another in the intestine [5]. The team then paired up these data with measurements of a set of more than 1,300 blood proteins from the children that provide “readouts” of their biological state.

Their investigation identified a network of 15 bacterial species that consistently interact in the gut microbiomes of Bangladeshi children. This network became their means to characterize sensitively and accurately the development of a child’s microbiome and/or its relative state of repair.

Next, they turned to mice colonized with the same collections of microbes found in the intestines of the Bangladeshi children. Gordon’s team then tinkered with the animals’ diets in search of ingredients commonly consumed by young children in Bangladesh that also appeared to encourage a healthier, more mature microbiome. They did similar studies in young pigs, whose digestive and immune systems more closely resemble humans.

The Gordon team settled on three candidate microbiome-friendly formulations. Two included chickpea flour, soy flour, peanut flour, and banana at different concentrations; one of these two also included milk powder. The third combined chickpea flour and soy flour. All three contained similar amounts of protein, fat, and calories.

The researchers then launched a randomized, controlled clinical trial with children from a year to 18 months old with moderate acute malnutrition. These young children were enrolled into one of four treatment groups, each including 14 to 17 kids. Three groups received one of the newly formulated foods. The fourth group received standard rice-and-lentil-based meals.

The children received these supplemental meals twice a day for four weeks at the International Centre for Diarrhoeal Disease Research followed by two-weeks of observation. Mothers were encouraged throughout the study to continue breastfeeding their children.

The formulation containing chickpea, soy, peanut, and banana, but no milk powder, stood out above the rest in the study. Children taking this supplement showed a dramatic shift toward a healthier state as measured by those more than 1,300 blood proteins. Their gut microbiomes also resembled those of healthy children their age.

Their new findings published in the journal Science offer the first evidence that a therapeutic food, developed to support the growth and development of a healthy microbiome, might come with added benefits for children suffering from malnutrition. Importantly, the researchers took great care to design the supplements with foods that are readily available, affordable, culturally acceptable, and palatable for young children in Bangladesh.

A month isn’t nearly long enough to see how the new foods would help children grow and recover over time. So, the researchers are now conducting a much larger study of their leading supplement in children with histories of malnutrition, to explore its longer-term health effects for them and their microbiomes. The hope is that these new foods and others adapted for use around the world soon will help many more kids grow up to be healthy adults.

References:

[1] Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, Chen RY, Subramanian S, Cowardin CA, Meier MF, O’Donnell D, Talcott M, Spears LD, Semenkovich CF, Henrissat B, Giannone RJ, Hettich RL, Ilkayeva O, Muehlbauer M, Newgard CB, Sawyer C, Head RD, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Hossain MI, Islam M, Choudhury N, Sarker SA, Huq S, Mahmud I, Mostafa I, Mahfuz M, Barratt MJ, Ahmed T, Gordon JI. Science. 2019 Jul 12;365(6449).

[2] Childhood Malnutrition. World Health Organization

[3] Persistent gut microbiota immaturity in malnourished Bangladeshi children. Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, Benezra A, DeStefano J, Meier MF, Muegge BD, Barratt MJ, VanArendonk LG, Zhang Q, Province MA, Petri WA Jr, Ahmed T, Gordon JI. Nature. 2014 Jun 19;510(7505):417-21.

[4] Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Blanton LV, Charbonneau MR, Salih T, Barratt MJ, Venkatesh S, Ilkaveya O, Subramanian S, Manary MJ, Trehan I, Jorgensen JM, Fan YM, Henrissat B, Leyn SA, Rodionov DA, Osterman AL, Maleta KM, Newgard CB, Ashorn P, Dewey KG, Gordon JI. Science. 2016 Feb 19;351(6275).

[5] A sparse covarying unit that describes healthy and impaired human gut microbiota development. Raman AS, Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Subramanian S, Kang G, Bessong PO, Lima AAM, Kosek MN, Petri WA Jr, Rodionov DA, Arzamasov AA, Leyn SA, Osterman AL, Huq S, Mostafa I, Islam M, Mahfuz M, Haque R, Ahmed T, Barratt MJ, Gordon JI. Science. 2019 Jul 12;365(6449).

Links:

Childhood Nutrition Facts (Centers for Disease Control and Prevention)

Gordon Lab (Washington University School of Medicine in St. Louis)

NIH Human Microbiome Project

International Centre for Diarrhoeal Disease Research (Dhaka, Bangladesh)

NIH Support: National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Center for Advancing Translational Sciences; National Cancer Institute


Gut-Dwelling Bacterium Consumes Parkinson’s Drug

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Gut bacteria eating a pill

Scientists continue to uncover the many fascinating ways in which the trillions of microbes that inhabit the human body influence our health. Now comes yet another surprising discovery: a medicine-eating bacterium residing in the human gut that may affect how well someone responds to the most commonly prescribed drug for Parkinson’s disease.

There have been previous hints that gut microbes might influence the effectiveness of levodopa (L-dopa), which helps to ease the stiffness, rigidity, and slowness of movement associated with Parkinson’s disease. Now, in findings published in Science, an NIH-funded team has identified a specific, gut-dwelling bacterium that consumes L-dopa [1]. The scientists have also identified the bacterial genes and enzymes involved in the process.

Parkinson’s disease is a progressive neurodegenerative condition in which the dopamine-producing cells in a portion of the brain called the substantia nigra begin to sicken and die. Because these cells and their dopamine are critical for controlling movement, their death leads to the familiar tremor, difficulty moving, and the characteristic slow gait. As the disease progresses, cognitive and behavioral problems can take hold, including depression, personality shifts, and sleep disturbances.

For the 10 million people in the world now living with this neurodegenerative disorder, and for those who’ve gone before them, L-dopa has been for the last 50 years the mainstay of treatment to help alleviate those motor symptoms. The drug is a precursor of dopamine, and, unlike dopamine, it has the advantage of crossing the blood-brain barrier. Once inside the brain, an enzyme called DOPA decarboxylase converts L-dopa to dopamine.

Unfortunately, only a small fraction of L-dopa ever reaches the brain, contributing to big differences in the drug’s efficacy from person to person. Since the 1970s, researchers have suspected that these differences could be traced, in part, to microbes in the gut breaking down L-dopa before it gets to the brain.

To take a closer look in the new study, Vayu Maini Rekdal and Emily Balskus, Harvard University, Cambridge, MA, turned to data from the NIH-supported Human Microbiome Project (HMP). The project used DNA sequencing to identify and characterize the diverse collection of microbes that populate the healthy human body.

The researchers sifted through the HMP database for bacterial DNA sequences that appeared to encode an enzyme capable of converting L-dopa to dopamine. They found what they were looking for in a bacterial group known as Enterococcus, which often inhabits the human gastrointestinal tract.

Next, they tested the ability of seven representative Enterococcus strains to transform L-dopa. Only one fit the bill: a bacterium called Enterococcus faecalis, which commonly resides in a healthy gut microbiome. In their tests, this bacterium avidly consumed all the L-dopa, using its own version of a decarboxylase enzyme. When a specific gene in its genome was inactivated, E. faecalis stopped breaking down L-dopa.

These studies also revealed variability among human microbiome samples. In seven stool samples, the microbes tested didn’t consume L-dopa at all. But in 12 other samples, microbes consumed 25 to 98 percent of the L-dopa!

The researchers went on to find a strong association between the degree of L-dopa consumption and the abundance of E. faecalis in a particular microbiome sample. They also showed that adding E. faecalis to a sample that couldn’t consume L-dopa transformed it into one that could.

So how can this information be used to help people with Parkinson’s disease? Answers are already appearing. The researchers have found a small molecule that prevents the E. faecalis decarboxylase from modifying L-dopa—without harming the microbe and possibly destabilizing an otherwise healthy gut microbiome.

The finding suggests that the human gut microbiome might hold a key to predicting how well people with Parkinson’s disease will respond to L-dopa, and ultimately improving treatment outcomes. The finding also serves to remind us just how much the microbiome still has to tell us about human health and well-being.

Reference:

[1] Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP. Science. 2019 Jun 14;364(6445).

Links:

Parkinson’s Disease Information Page (National Institute of Neurological Disorders and Stroke/NIH)

NIH Human Microbiome Project

Balskus Lab (Harvard University, Cambridge, MA)

NIH Support: National Institute of General Medical Sciences; National Heart, Lung, and Blood Institute


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