New study led by John Haran will follow elderly participants from Worcester area for two years
UMass Medical School researchers have been awarded a $3.3 million, four-year National Institute on Aging grant to explore new understanding of how the gut microbiome influences cognitive functioning among elders living with Alzheimer’s disease.
Principal investigator John P. Haran, MD, PhD, associate professor of emergency medicine and microbiology & physiological systems and clinical director of the UMass Center for Microbiome Research, said the new study goes beyond previous research by bridging microbiome associations with Alzheimer’s disease with the mechanism of causality.
“We’re trying to connect the microbiome and the local immune system, at the intestinal epithelial layer, to cognitive functioning, and beyond that to cerebral immune system functioning,” Dr. Haran said. “That’s the big thing: What is the mechanism that is functioning here that the microbiome is acting on?”
Researchers will follow over two years the cognitive functioning and gut microbiome characteristics among elders in a variety of settings; utilize a series of human and animal lab experiments to determine how the microbiome can induce intestinal inflammation and how this correlates back to systemic inflammation; and study the microbiome metabolic product differences to explain how these products can influence microglia functioning, which affects the immune system.
Research published last year by Haran and Beth McCormick, PhD, the Worcester Foundation for Biomedical Research Chair, professor and vice chair of microbiology & physiological systems, and founding director of the Center for Microbiome Research, showed that residents in nursing homes with Alzheimer’s disease have distinctly different gut microbiomes than residents with other forms of dementia.
Their preliminary work was also supported by an Alzheimer’s Association New to the Field research grant.
“What allows us to even further infer causality in the new study is the longitudinal assessment, because now we have a scale and a patient population with a disease that we can track through their cognitive decline, while at the same time assess what’s happening with their gut microbial composition and function, as well as with levels of inflammatory markers in their serum,” Dr. McCormick said.
Haran, who studies the spread of drug resistant organisms in nursing homes and the hospital, said 260 elders will be enrolled in the study, with roughly half living with Alzheimer’s disease. Half of the participants will be living in a nursing home and half will be at home. Researchers are working with the Worcester Senior Center and other community organizations to recruit participants. Included in the study will be caregivers for elders at home with Alzheimer’s disease, who will serve as a matched control and help with sample collection.
Haran and McCormick said the study will provide deeper insight into subsets of Alzheimer’s dementia and the microbiome gut-brain connection. That knowledge will help propel development of new therapeutics.
“It’s not as simple as saying, just go home and eat more leafy greens,” Haran said. “It’s tricky because nobody knows what the right healthy microbiome is.”
He said, “Where this grant is going in future work is, we’re trying to identify specifically what parts of the microbiome can help elders avoid this cognitive decline and then we’re going to try to be able to reproduce that in animal models and then back into humans.”
“It comes down to what the composition of these microbial communities are doing in terms of their metabolic output and how this is connected to microglia functioning,” said McCormick.
McCormick added, “This is a remarkable example of a multidisciplinary effort coming together, which could have exponential value in a very important disease area.”
Along with Haran and McCormick, collaborators include Paul L. Greer, PhD, assistant professor of medicine, who focuses on brain physiology; Vanni Bucci, PhD, associate professor of microbiology & physiological systems, an expert in machine learning and artificial intelligence; and Doyle Ward, PhD, associate professor of microbiology & physiological systems, an expert in bacterial metagenomics and genomics.