The power of patient reported feedback: Part 1

January 29th, 2016 by Amy Proal
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Last year I was invited to give a speech at a scientific conference that examined the role of the microbiome in autoimmune disease – concepts I describe in this Current Opinion in Rheumatology journal article. Our research team had also developed an immunostimulatory treatment for autoimmune disease based off concepts in the paper. Doctors in at least a dozen countries were using the treatment with their patients, often with success.

I didn’t discuss this treatment in my speech, but made the following statement during the last twenty seconds of the talk: “We have developed an immunostimulatory treatment that patients are using in conjunction with their doctors. If you’re interested in any of our case histories find me later.” Continue reading

Of mice and not men: can complex human inflammatory disease be studied in mice?

January 13th, 2016 by Amy Proal
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Much of my junior year at Georgetown University was spent in an animal research facility. Along with my undergraduate thesis mentor and several fellow students, I studied the impact of a high-fat (ketogenic) diet in Sprague-Dawley rats. We had read reports in which human children with epilepsy who were fed this ketogenic diet experienced fewer seizures. Now we were attempting to ascertain whether rats eating a ketogenic chow would experience seizures at a different rate than those eating a chow rich in carbohydrates.

I graduated before the research project was complete, but later learned that some differences in seizure incidence between the two groups of rats were identified. Yet the team was never able to figure out the root cause underlying these differences.

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Mothers and microbes, Part 2: The placental, breast milk, and breast tissue microbiomes

December 27th, 2015 by Amy Proal
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While the vaginal microbiome has received a great deal of attention from the research community, recent research also indicates that microbes persist in the womb, where they come in contact with a fetus before it is born. Studies demonstrating the presence of microbes in the amniotic fluid have now been bolstered by the discovery of a placental microbiome. Dysregulation of this placental microbiome by pathogens has also been associated with preterm birth and low infant birth weight.

Consistent with the presence of a placental microbiome, naturally-born infants often harbor microbes not commonly found in the vagina. For example, while vaginal communities are often composed of up to 80 percent Lactobacillus, the microbiomes of newborn infants contain high levels of other taxa, such as Actinobacteria, Proteobacteria, and Bacteroides. Infants appear to have acquired these microbes in the womb, and not during the birthing process. Continue reading

Mothers and microbes, Part 1: The vaginal microbiome in health and disease

December 20th, 2015 by Amy Proal
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“Like mother, like daughter.” The phrase is often invoked to describe how children resemble their parents. While we know that human genes are passed from generation to generation, an expanding body of research now shows that many microbiome populations are also inherited. The microbes a child inherits are acquired from both parents and even siblings. However, microbial populations inherited from the mother have a particularly strong impact on a child’s development and health.

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Stanford researchers: The immune response is shaped by microbes rather than human genes

December 11th, 2015 by Amy Proal
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Two different people are riding the subway. A third person coughs on these individuals over the course of their trip. One person gets the flu, but the other doesn’t. Somewhere nearby, two more people accidentally eat a piece of meat that wasn’t correctly refrigerated. One develops food poisoning, but the other remains healthy. What factors contribute to these different outcomes?

The key factor is the immune response. Immune cells such as macrophages and granulocytes kill invading microbes. Other immune proteins called cytokines and chemokines aid cellular communication and stimulate the movement of cells towards sites of inflammation. Immune growth factors also form part of the immune response by stimulating the proliferation of specific tissues. If profiles of these immune parameters differ between individuals, then their ability to respond to pathogens will also vary. Continue reading

Industry ties deeply influence guidelines for calcium/vitamin D intake

December 3rd, 2015 by Amy Proal
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Are you taking vitamin D and calcium for bone health? If so, a new analysis makes it clear that the supplement guidelines you follow are often shaped by money rather than science. In July, Andrew Grey and Mark Bolland (University of Auckland, New Zealand) published an article in the British Medical Journal. Their article, “Web of industry-advocacy, and academia in the management of osteoporosis,” powerfully illustrates how industry ties and financial gain have tarnished the legitimacy of worldwide vitamin D and calcium supplementation guidelines.

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Disease-induced solitary confinement and the gut microbiome

November 25th, 2015 by Amy Proal
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What happens when a person dies alone, with no relatives or friends to provide information or help? Why do people die alone in some of the most populated areas of the world? A recent article in the New York Times delves into the topic by examining the life of George Bell, a man found dead in his Jackson Heights apartment in Queens, New York. I live just ten minutes away. His body was found after it had rotted to the point where neighbors noticed a smell. He knew only one person during the last decade of his life, a man he sometimes met at a bar. Yet with no family or friends in his life, it took over three months to identify his corpse.

I think that many readers may have started reading the article assuming that George Bell would, at the very least, have done some bad things to others. After all, before his death at 72, he spent nearly a decade living completely alone, with negligible social contact. How could that happen to an average, generally nice individual?

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Fungi in the Alzheimer’s brain and changing views on amyloid beta

November 18th, 2015 by Amy Proal
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Fungal species in different brain regions of patients with Alzheimers. (Soscia et al.)

Fungal species in different brain regions of patients with Alzheimers. (Pisa et al.)

Just a few days after writing my last post on microbes in the brain, I read a study that shows even more evidence of chronic infectious agents in brain tissue. In a paper published this month, Pisa and team at the Universidad Autónoma de Madrid studied the brains of patients with Alzheimer’s disease (AD). They found that all eleven AD brains studied were infected with a range of fungal organisms.

I am not surprised by the discovery. For one thing, inflammation of the central nervous system and immune activation play a major role in driving the Alzheimer’s disease process. Indeed, a number of cytokines, or immune system signaling molecules, are elevated in the brain of AD patients. This strongly suggests an activated immune response against pathogens. These cytokines include interleukins, tumor necrosis factor-α, and interferon-γ. Continue reading

The newly discovered lymphatic system in the brain, and a possible brain microbiome

November 11th, 2015 by Amy Proal
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The brain has long been considered to be a sterile organ, an “immunoprivileged” body site that microbes cannot directly enter and infect. Most medical textbooks still contend that microbes cannot enter the healthy brain due to a layer of endothelial cells that separate the brain from the body. This layer of cells, called the blood-brain barrier, is believed to separate circulating blood in the brain from fluid in the central nervous system and the rest of the body. Current dogma also dictates that bacteria are too large in shape and size to penetrate this barrier.

Despite this blood-brain “barrier”, researchers have regularly detected at least some pathogens in the brain: Borrelia, Group B streptococci, and Treponema pallidum – to name a just few. Such microbes’ presence is generally explained by the hypothesis that the blood-brain barrier becomes more permeable under conditions of inflammation. Certain pathogens, especially those able to survive inside of the cells of the immune system, are then considered capable of crossing into the brain’s circulatory system.

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Microbial signaling molecules drive cancer development

November 3rd, 2015 by Amy Proal
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For the past century, scientists have associated certain microbes or microbial populations with the development of cancer. A recent study by researchers at Ghent University in Belgium expands on this research by demonstrating a previously undiscovered mechanism by which gastrointestinal microbes can drive cancer processes. The study, Crosstalk between the microbiome and cancer cells by quorum sensing peptides shows how quorum sensing peptides synthesized by common gut bacteria can directly influence cancer cell growth and tumor formation.

Before proceeding, if you want to brush up on the concept of quorum sensing itself, watch this fascinating lecture by Princeton microbiologist Bonnie Bassler. If not, remember that quorum sensing peptides are produced by bacteria for purposes of communication with other microbes in their environment. Or that is their primary function. The above study shows that, at least in the laboratory, these peptides can additionally alter the expression of human genes.

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