Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

bone density

Microbiome critical for bone hormone action

Intestinal microbes are necessary for the actions of an important hormone regulating bone density, according to two papers from the Emory Microbiome Research Center. The papers represent a collaboration between Roberto Pacifici, MD and colleagues in the Department of Medicine and laboratory of Rheinallt Jones, PhD in the Department of Pediatrics.

Together, the results show how probiotics or nutritional supplementation could be used to modulate immune cell activity related to bone health. The two papers, published in Nature Communications and Journal of Clinical Investigation, are the first reports of a role for intestinal microbes in the mechanism of action of PTH (parathyroid hormone), Pacifici says.

PTH increases calcium levels in the blood and can either drive bone loss or bone formation, depending on how it is produced or administered. Continuous excessive production of PTH, or primary hyperparathyroidism, is a common endocrine cause of osteoporosis. Yet in another context, intermittent external PTH stimulates bone formation, and is an FDA-approved treatment for osteoporosis – also used off-label for fracture repair in athletes. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

How intestinal bacteria affect bone formation

Helpful intestinal bacteria may stimulate bone formation via butyrate, according to a recent paper in Immunity. Butyrate increases bone formation through its regulation of T cells, Emory researchers report.

The finding adds to evidence for beneficial effects of butyrate and other SCFA (short chain fatty acid) metabolites, which are produced by bacterial fermentation of fiber in the intestines.

Roberto Pacifici and colleagues had observed that probiotic supplements protected female mice from the loss of bone density occurring after ovary removal, a simulation of the hormonal changes of menopause. Probiotic bacteria could also stimulate bone formation in mice with intact ovaries, the researchers found.

The new Immunity paper shows how this effect is produced. The probiotic bacteria do not make butyrate themselves, but they encourage the growth of other Clostridum bacteria that do produce butyrate. Read more

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Probiotics for bone health study heads into clinic

Probiotic supplements can protect female mice from the loss of bone density that occurs after having their ovaries removed, researchers at Emory and Georgia State reported a couple years ago.

Roberto Pacifici, MD

This finding, published in Journal of Clinical Investigation, had clear implications for the treatment of osteoporosis in post-menopausal women. Prompted by external emails, Lab Land learned that the Emory investigators are now continuing their research in the clinic.

Endocrinologist/osteoimmunologist Roberto Pacifici and colleague Jessica Alvarez are conducting a double-blind study for women aged 50-65, using VSL3, a widely available and inexpensive dietary supplement. Participants would take the supplement or placebo for a year. More information is available here.

In mice, the loss of estrogen increases gut permeability, which allows bacterial products to activate immune cells in the intestine. In turn, immune cells release signals that break down bone. It appears that probiotics both tighten up the permeability of the gut and dampen inflammatory signals that drive the immune cells. Read more

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Bone-strengthening particles stimulate autophagy

Neale Weitzmann and George Beck have been publishing a series of papers describing how silica nanoparticles can increase bone mineral density in animals. Their findings could someday form the basis for a treatment for osteoporosis.

In 2012, we posted an article and video on this topic. We wanted to call attention to a few of the team’s recent papers, one of which probes the mechanism for a remarkable phenomenon: how can very fine silica particles stimulate bone formation?

The particles’ properties seem to depend on their size: 50 nanometers wide – smaller than a HIV or influenza vision. In a 2014 ACS Nano paper, Beck, Weitzmann and postdoc Shin-Woo Ha show that the particles interact with particular proteins involved in the process of autophagy, a process of “self digestion” induced by stress.

“These studies suggest that it is not the material per se that stimulates autophagy but rather size or shape,” they write. Read more

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