Michigan State University Research Foundation Professor Laura McCabe, Ph.D., has been named a 2024 fellow of the American Association for the Advancement of Science (AAAS).
Dr. McCabe, professor in the Departments of Physiology and Radiology within the MSU College of Osteopathic Medicine, was honored for her research that explores how probiotics benefit bone health and can prevent bone loss under a variety of conditions. She is also associate vice president of Research Regularity Support in MSU’s Office of Research and Innovation.
AAAS is the world’s largest general scientific society, which recognizes distinguished individuals as fellows for their contributions to science and society.
“I am honored to be named as an AAAS Fellow,” Dr. McCabe said. “This achievement would not have been possible without the crucial federal funding that supported our research, as well as outstanding students and collaborators at MSU. It truly takes a team, and together we linked gut health to bone health and are identifying ways to treat and prevent osteoporosis.”
One out of every two women and one out of every five men over the age of 50 will have an osteoporotic fracture in their lifetime because of low bone density. Bone breaks can lead to complications, loss of independence, required use of a cane or walker, depression and mortality.
Primary osteoporosis, the leading cause of osteoporosis, develops in women as the loss of estrogen after menopause increases the risk of bone loss. Secondary osteoporosis happens in people with various conditions that can cause bone loss, including diseases like inflammatory bowel disease (IBS) or diabetes. Long-term use of certain anti-inflammatory medications or steroids, such as prednisone, can also significantly increase the risk of osteoporosis.
Connecting the gut microbiota to bone health
After earning a Ph.D. in gastrointestinal physiology at the University of Chicago in 1991 and completing post-doctoral work in bone molecular biology at UMass Medical School in 1995, Dr. McCabe came to MSU to continue her research on the gastrointestinal (GI) tract. Part of her job involved teaching GI physiology to first- and second-year medical students at the MSU College of Osteopathic Medicine.
However, it was Dr. McCabe’s research in bone that grew and received significant funding, so her lab focused on bone and not gut. About 10 years after her arrival at MSU, a grant call from The Crohn’s & Colitis Foundation emerged that focused on the question of exactly how colitis, inflammation of the colon, affects bone density.
“I thought, ‘That’s me,’” Dr. McCabe said. “I’m gut, I’m bone, I’m applying. And we got it.”
The Crohn’s & Colitis Foundation grant prompted Dr. McCabe to start thinking more deeply about inflammation in the digestive system and the mechanisms that occur to produce bone loss. One day, she happened to run into a colleague at MSU, a microbiologist who was studying a probiotic with anti-inflammatory properties. They soon began collaborating with a Swedish healthcare company to patent the use of a probiotic as a preventative against osteoporosis.
“I thought, ‘We know that inflammation causes bone loss, but what if we did the reverse and we reduced inflammation, would it be possible to benefit bone health?’” she said. “And that led us to try it in mice in osteoporosis-producing conditions. It was so exciting because we found that we could prevent bone loss by giving the mice this probiotic.”
Probiotics are live microorganisms, typically bacteria that improve the balance of beneficial bacteria in the gut and can help improve digestion and support immune health. Probiotics can come from certain foods or as a dietary supplement. According to Dr. McCabe, probiotics can increase bone density in healthy individuals and can protect against primary and secondary osteoporosis. Her lab has shown that intestinal inflammation causes bone loss, and it has demonstrated that probiotics can benefit gut health, increase bone density in healthy male mice and prevent bone loss in many conditions.
One of the things Dr. McCabe’s lab identified was that inflammation triggers increased permeability of the gut, which is linked to bone loss. The GI tract functions well when a healthy balance of “good” and “bad” bacteria exists in the microbiome. The microbiome is a unique ecosystem made up of trillions of microscopic organisms that aid in digestion and absorption of nutrients from food. A healthy diet – with fiber (a prebiotic) – essentially promotes the expansion of “good” bacteria in the gut while minimizing the growth of “bad” bacteria.
Dr. McCabe’s research focuses on the gut as a therapeutic target to treat osteoporosis. Her lab investigates the mechanisms behind the connection between GI health and bone health, as well as what kind of foods and supplements can be used to enhance microbiota composition and barrier function.
“What we found is that under conditions of GI inflammation the intestinal barrier is leaky, and part of that is linked to bad bacteria in your microbiota,” Dr. McCabe explained. “There are all kinds of different strains. You want a healthy composition of bacteria that reduces inflammation and strengthens the barrier. As bad bacteria increase, then you get more inflammation and the barrier opens more, which can lead to bone loss.”
Exploring the gut’s relationship to bones and beyond
One of the most amazing things about the human skeleton is how it continually rebuilds itself. The skeleton is subjected to a variety of stresses and strains that lead to micro-cracks and damage over time. Osteoclasts, the cells that break down old or damaged bone tissue, work in synchrony with osteoblasts, the cells that make new bone tissue in the process of bone remodeling.
“Think of bone like a house,” Dr. McCabe said. “If you get a little crack in the wall, you need to repair it. Similarly, the osteoclasts see those cracks and resorb the bone around the crack. As they eat it, growth factors from the bone matrix are released, and then local cells mature into activated osteoblasts. The osteoblasts build bone and repair the damaged bone. You want that because if you don’t remodel, the bone mineral composition is going to get older and isn’t as strong. So, it’s a beautiful process that the bone goes through, making the bone mineral its optimal new content. Every 10 years, your whole bone structure is replaced. There’s no site that doesn’t get redone, just like you would try to keep your house new with renovations.”
It's no secret that a diet rich in calcium and vitamin D, along with regular exercise, is important for strong bones. But prebiotics, probiotics and postbiotics are also essential for a healthy digestive ecosystem that fuels bone growth. Prebiotic foods, like fruits and vegetables, are high in fiber and serve as food for beneficial gut bacteria. Probiotic foods, such as yogurt, are fermented or contain beneficial live bacteria that can alter the microbiome. Postbiotics are the products produced by probiotic digestion of fiber and other foods. These beneficial byproducts include vitamins, amino acids, and fatty acids.
One natural source of prebiotics under study at Dr. McCabe’s lab is prunes. She says prunes benefit bone density markedly, even in healthy mice.
Her internationally recognized research program has been funded through various grants from the National Institutes of Health, National Science Foundation and several private foundations. She holds several patents related to the treatment of osteoporosis and her research is leading to new patents, therapeutics and ideas. Dr. McCabe’s goal is to eventually move toward human studies.
“Our work is the compilation of various contributions from students (including two D.O.-Ph.D. students) and collaborators (including Drs. Britton, Parameswaran, and Gallo) across campus,” she said. “We’re looking at bone, but other MSU researchers are also looking at gut-brain or gut-cardiovascular connections. For example, we are looking at Dr. Gallo’s team, where we are investigating chemotherapy use in cancer and how we might target the gut to counteract the side effects of chemotherapy. There are many iterations to see how we can maximize our knowledge of the gut to people’s health under treatments, health under disease and overall health of the body.”
Dr. McCabe admits she makes sure she gets a good amount of probiotics in her body, and, yes, she eats prunes. Her journey at MSU began 28 years ago. She credits her teaching experience at MSUCOM for launching the trajectory that her research has taken in discovering new connections between gut health and bone density.
“Certainly, it was my teaching and mentoring of medical students in COM that was really what kept me prepared for when the original grant call came – to have the gastrointestinal physiology (knowledge) at such a high level to teach those students and maintain my creativity in that area really helped me to be ready to draw these links together,” Dr. McCabe said.
“It’s just so interesting in a career, like you can’t predict things and how they all come together at some point. All of your experiences are preparing you. So, what you think is maybe a detour or distracting you, can actually become useful.”
By Lynn Waldsmith